ascorbic-acid and diphenyldiselenide

The ability of diphenyl diselenide [(PhSe)2] to attenuate oxidative damage was evaluated in the liver, gills, brain, and muscle of carp (Cyprinus carpio) and silver catfish (Rhamdia quelen) experimentally exposed to fipronil (FPN). Initially, the fish were fed a diet without (PhSe)2 or a diet containing 3.0 mg/kg of (PhSe)2 for 60 days. After the 60-day period, the fish were exposed to 0.65 µg/L of FPN for 192 h. The results showed that carp exposed to FPN and not fed with (PhSe)2 exhibited acetylcholinesterase (AChE) inhibition in brain and muscle, and increased thiobarbituric acid-reactive substance (TBARS) in liver, gills, and brain. Furthermore, FPN decreased nonprotein thiols (NPSH) and δ-aminolevulinate dehydratase (δ-ALA-D) in carp liver and gills, and increased plasma glucose and protein levels. In silver catfish, FPN inhibited AChE and increased TBARS levels in muscle. In addition, glutathione S-transferase (GST) decreased in liver and muscle, and plasma glucose was increased. (PhSe)2 reversed some of these effects. It prevented the increase in TBARS levels in liver, gills, and brain in carp and in silver catfish muscle, and reversed the increase in plasma glucose levels in both species. Additionally, (PhSe)2 increased the NPSH levels in carp and silver catfish that had decreased in response to FPN exposure. However, (PhSe)2 was not effective in reversing the AChE inhibition in brain and muscle or the δ-ALA-D decrease in carp liver. Thus, (PhSe)2 protects tissues of both species of fish, mainly by preventing or counteracting the effects of FPN, on TBARS levels, antioxidants, and present anti-hyperglycemic property.

Topics: Acetylcholinesterase; Aminolevulinic Acid; Animals; Ascorbic Acid; Benzene Derivatives; Biomarkers; Brain; Carps; Catfishes; Dietary Supplements; Fish Proteins; Fresh Water; Gills; Glutathione Transferase; Insecticides; Liver; Muscles; Organoselenium Compounds; Oxidative Stress; Pyrazoles; Sulfhydryl Compounds; Thiobarbituric Acid Reactive Substances

In this study, the protective effects of diphenyl diselenide [(PhSe)2] on quinclorac- induced toxicity were investigated in silver catfish (Rhamdia quelen). The fish were fed for 60 days with a diet in the absence or in the presence of 3.0 mg/Kg (PhSe)2. Animals were further exposed to 1 mg/L quinclorac for 8 days. At the end of experimental period, fish were euthanized and biopsies from liver and gills, as well as blood samples, were collected. The cortisol and metabolic parameters were determined in plasma, and those enzyme activities related to osmoregulation were assayed in the gills. In liver, some important enzyme activities of the intermediary metabolism and oxidative stress-related parameters, such as thiobarbituric acid-reactive substance (TBARS), protein carbonyl, catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), nonprotein thiols (NPSH) and ascorbic acid contents were also evaluated. Compared to the control group, quinclorac exposure significantly decreased hepatosomatic index and increased cortisol and lactate values in plasma. Moreover, the activities of fructose biphosphatase (FBPase), glucose-6-phosphate dehydrogenase (G6Pase), glycogen phosphorilase (GPase) and aspartate aminotransferase (AST) were significantly increased in liver. Quinclorac also induced lipid peroxidation while the activity of SOD, NPSH and ascorbic acid levels decreased in the liver. However, dietary (PhSe)2 reduced the herbicide-induced effects on the studied parameters. In conclusion, (PhSe)2 has beneficial properties based on its ability to attenuate toxicity induced by quinclorac by regulating energy metabolism and oxidative stress-related parameters.

Topics: Animals; Ascorbic Acid; Benzene Derivatives; Catalase; Catfishes; Diet; Dietary Supplements; Fish Proteins; Glutathione Transferase; Herbicides; Liver; Organoselenium Compounds; Oxidative Stress; Protective Agents; Quinolines; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

The study investigated the capacity of diphenyl diselenide [(PhSe)2] (3.0mg/kg), on reduce the oxidative damage in liver, gills and muscle of carp and silver catfish exposed to clomazone (192h). Silver catfish exposed to clomazone showed increased thiobarbituric acid-reactive substance (TBARS) in liver and muscle and protein carbonyl in liver and gills. Furthermore, clomazone in silver catfish decrease non-protein thiols (NPSH) in liver and gills and glutathione peroxidase and ascorbic acid in liver. (PhSe)2 reversed the effects caused by clomazone in silver catfish, preventing increases in TBARS and protein carbonyl. Moreover, NPSH and ascorbic acid were increased by values near control. The results suggest that (PhSe)2 attenuated the oxidative damage induced by clomazone in silver catfish. The clomazone no caused an apparent situation of oxidative stress in carp, showing that this species is more resistant to this toxicant. Altogether, the containing (PhSe)2 diet helps fish to increase antioxidants defenses.

Topics: Animal Feed; Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Carps; Catalase; Catfishes; Diet; Dietary Supplements; Gills; Glutathione Peroxidase; Glutathione Transferase; Herbicides; Isoxazoles; Liver; Muscles; Organoselenium Compounds; Oxazolidinones; Oxidative Stress; Protein Carbonylation; Species Specificity; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Water Pollutants, Chemical

This study aimed to investigate the beneficial effect of diphenyl diselenide (PhSe)₂ on paraquat (PQ) induced alterations in rats liver. Adult male Wistar rats received (PhSe)₂ at 10 mg kg(-1), by oral administration (p.o.), during five consecutive days. Twenty-four hours after the last (PhSe)₂ dose, rats received PQ at 15 mg kg(-1), in a single intraperitoneally injection (i.p.). Seventy-two hours after PQ exposure, animals were sacrificed by decapitation for blood and liver samples obtainment. Histological alterations induced by PQ exposure, such as inflammatory cells infiltration and edema, were prevented by (PhSe)₂ administration. Moreover, (PhSe)₂ prevented hepatic lipid peroxidation (LPO) induced by PQ and was effective in reducing the myeloperoxidase (MPO) activity in liver, which was enhanced by PQ exposure. (PhSe)₂ also was effective in protecting against the reduction in ascorbic acid and non-protein thiols (NPSH) levels induced by PQ. The inhibition of glutathione S-transferase (GST) activity, in rats exposed to PQ, was normalized by (PhSe)₂ pre-treatment, whereas the inhibition of catalase (CAT) activity was not prevented by (PhSe)₂. The serum alkaline phosphatase (ALP) inhibition, induced by PQ administration, was also prevented by (PhSe)₂ pre-treatment. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were not modified by PQ and/or (PhSe)₂ administration. Therefore, (PhSe)₂ pre-treatment was effective in protecting against the hepatic alterations induced by PQ in rats. This protective effect can involve the antioxidant and anti-inflammatory properties of (PhSe)₂.

Topics: Animals; Ascorbic Acid; Benzene Derivatives; Catalase; Chemical and Drug Induced Liver Injury; Glutathione Transferase; Herbicides; Lipid Peroxidation; Liver; Liver Function Tests; Male; Organoselenium Compounds; Paraquat; Peroxidase; Rats; Rats, Wistar; Sulfhydryl Compounds

The occurrence of pollutants in the aquatic environment can produce severe toxic effects on non-target organisms, including fish. These sources of contamination are numerous and include herbicides, which represent a large group of toxic chemicals. Quinclorac, an herbicide widely applied in agriculture, induces oxidative stress due to free radical generation and changes in the antioxidant defense system. The aim of this study was to assess if dietary diphenyl diselenide (PhSe)₂ has a protective effect in tissues of fish species Cyprinus carpio exposed to the quinclorac herbicide. The fish were fed with either a standard or a diet containing 3.0 mg/Kg of diphenyl diselenide for 60 d. After were exposed to 1 mg/L of Facet® (quinclorac commercial formulation) for 192 h. At the end of the experimental period, parameters as thiobarbituric acid-reactive substance levels (TBARS), protein carbonyl, catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), nonprotein thiols (NPSH) and ascorbic acid in the liver, gills, brain and muscle were evaluated in Cyprinus carpio. In fish exposed to quinclorac and feeding with standard diet TBARS levels increased in liver and gills. However, SOD activity decreases in liver whereas no alterations were observed in catalase activity in this tissue. Quinclorac also decrease GST activity in liver and brain, NPSH in brain and muscle and ascorbic acid in muscle. Concerning protein carbonyl exposed to herbicide the fish did not show any alterations. The diphenyl diselenide supplemented diet reversed these effects, preventing increases in TBARS levels in liver and gills. GST activity was recovered to control values in liver. NPSH levels in brain and muscle increased remain near to control values. These results indicated that dietary diphenyl diselenide protects tissues against quinclorac induced oxidative stress ameliorating the antioxidant properties.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Biomarkers; Carps; Catalase; Gills; Glutathione Transferase; Herbicides; Liver; Muscles; Organoselenium Compounds; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

The effects of 4,4'-dichloro-diphenyl diselenide (ClPhSe)(2) on the toxicity induced by mercuric chloride (HgCl(2)) were investigated and compared with diphenyl diselenide (PhSe)(2). Mice received HgCl(2) for three days and, on the third day, received (PhSe)(2) or (ClPhSe)(2). The results verified that the administration of (ClPhSe)(2) in mice exposed to HgCl(2) increased renal δ-aminolevulinate dehydratase (δ-ALA-D), Na(+), K(+)-ATPase activities and non-protein thiol (NPSH) levels and also decreased thiobarbituric acid-reactive substances (TBARS) and ascorbic acid levels, when compared to mice exposed to HgCl(2)+(PhSe)(2). Plasma and urinary protein, hemoglobin and hematocrit levels and histological parameters were also ameliorated in mice exposed to HgCl(2)+(ClPhSe)(2). In addition, the hepatic damage in mice exposed to HgCl(2)+(PhSe)(2) was reduced in animals exposed to (ClPhSe)(2). To sum up, the introduction of a functional group (chloro) in the aromatic ring of diaryl diselenide reduced the toxicity of this compound in liver and kidney of mice exposed to HgCl(2).

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Dose-Response Relationship, Drug; Hazardous Substances; Kidney; Liver; Male; Mercuric Chloride; Mice; Organoselenium Compounds; Porphobilinogen Synthase; Thiobarbituric Acid Reactive Substances

Following our long-standing interest in the mechanisms involved in selenium toxicity, the aim of this work was to extend our previous studies to gain a better understanding of mercuric chloride (HgCl₂) + diphenyl diselenide (PhSe)₂ toxicity. Mice received one daily dose of HgCl₂ (4.6 mg kg(-1) , subcutaneously) for three consecutive days. Thirty minutes after the last injection of HgCl₂, mice received a single dose of (PhSe)₂ (31.2 mg kg(-1) , subcutaneously). Five hours after (PhSe)₂ administration, mice were euthanized and δ-aminolevulinate dehydratase, catalase (CAT), glutathione S-transferase (GST) and Na(+) , K(+) -ATPase activities as well as thiobarbituric acid-reactive substances (TBARS), ascorbic acid and mercury levels were determined in kidney and liver. Parameters in plasma (urea, creatinine, protein and erythropoietin), whole blood (hematocrit and hemoglobin) and urine (protein) were also investigated. HgCl₂ + (PhSe)₂ exposure caused a decrease in renal GST and Na(+) , K(+) -ATPase activities and an increase in renal ascorbic acid and TBARS concentrations when compared with the HgCl₂ group. (PhSe)₂ potentiated the increase in plasma urea caused by HgCl₂. HgCl₂ + (PhSe)₂ exposure caused a reduction in plasma protein levels and an increase in hemoglobin and hematocrit contents when compared with the HgCl₂ group. There was a significant reduction in hepatic CAT activity and an increase in TBARS levels in mice exposed to HgCl₂ + (PhSe)₂ when compared with the HgCl₂ group. The results demonstrated that (PhSe)₂ did not modify mercury levels in mice. In conclusion, (PhSe)₂ potentiated damage caused by HgCl₂ affecting mainly the renal tissue.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Benzene Derivatives; Catalase; Creatinine; Erythropoietin; Glutathione Transferase; Kidney; Liver; Male; Mercuric Chloride; Mercury; Mice; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Thiobarbituric Acid Reactive Substances; Urea

Ovarian hormone decline after menopause is linked to many pathophysiological reactions. Female rats submitted to ovariectomy are employed as a model of post-menopausal condition. This study investigated the effects of diphenyl diselenide (PhSe)(2) on body weight gain, intra-abdominal fat deposition, plasma lipid profile and hepatic oxidative stress in ovariectomized rats.. Female adult Wistar rats were ovariectomized (OVX rats) or sham-operated and divided into four groups: (i) sham-operated, (ii) (PhSe)(2), (iii) OVX and (iv) OVX + (PhSe)(2). (PhSe)(2) (5 mg/kg; 5 ml/kg, p.o.) was administered once a day for 30 days to groups (ii) and (iv). After that, rats were anaesthetized for blood sample gathering and submitted to euthanasia.. (PhSe)(2) (5 mg/kg) was effective in preventing the rise in body weight gain and intra-abdominal fat deposition induced in OVX rats. Although (PhSe)(2) was not effective in avoiding the increase in plasma total cholesterol and non-HDL levels induced in OVX rats, (PhSe)(2) reduced plasma triglycerides and augmented HDL levels in OVX rats. (PhSe)(2) also increased hepatic ascorbic acid levels, reduced glutathione content, glutathione S-transferase activity and restored catalase activity in liver of OVX rats.. These findings suggest that (PhSe)(2) could be a promising alternative to minimize menopause related symptoms.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Female; Hormones; Intra-Abdominal Fat; Lipids; Liver; Models, Animal; Obesity; Organoselenium Compounds; Ovariectomy; Oxidative Stress; Postmenopause; Rats; Rats, Wistar; Weight Gain

Although in vitro data from our previous studies show that the antioxidant effect and reactions of both diphenyl diselenide (DPDS) and dicholesteroyl diselenide (DCDS) towards thiol-containing proteins differ considerably, the present study sought to evaluate the interaction of both organodiselenides with thiol-containing proteins in vivo. Mice were injected subcutaneously with DPDS or DCDS previously dissolved in soya bean oil at doses of 0.5 mmol kg⁻¹ body weight for four consecutive days. The activities of delta aminolevulinic acid dehydratase (ALA-D), Na+/K+-ATPase, and isoforms of lactate dehydrogenase (LDH) and catalase were investigated. In addition, the antioxidant status of the mice was determined by measuring the levels of glutathione (GSH), vitamin C (Vit C) and thiobarbituric acid reactive substances. The results show that both diselenides significantly increased the levels of GSH and Vit C but did not markedly alter other antioxidant indices. With respect to the thiol-containing enzymes that were evaluated, DPDS and not DCDS caused a marked reduction in the activities of hepatic ALA-D; however, both diselenides inhibited all isoforms of LDH evaluated. In addition, the activities of cerebral Na+/K+-ATPase were not markedly inhibited by both diselenides, suggesting that this cerebral enzyme may not be a molecular target of organodiselenides toxicity. Taken together, the pharmacological and toxicological chemistry of organoselenium compounds is complex and multifactorial and is dependent on delicate equations which include vehicle solution, animal species and mode of delivery.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Catalase; Cholesterol; Glutathione; Injections, Subcutaneous; Isoenzymes; L-Lactate Dehydrogenase; Liver; Male; Mice; Organoselenium Compounds; Porphobilinogen Synthase; Proteins; Sodium-Potassium-Exchanging ATPase; Sulfhydryl Compounds; Thiobarbituric Acid Reactive Substances

Male albino rats with diabetes induced by the administration of streptozotocin (STZ) (45 mg/kg, i.v.) were treated with oral administration of diphenyl diselenide (DPDS) pre-dissolved in soya bean oil. A significant reduction in blood glucose levels was observed in STZ-induced diabetic rats treated with DPDS compared with an untreated STZ diabetic group. The pharmacological effect of DPDS was accompanied by a marked reduction in the level of glycated proteins, and restoration of the observed decreased levels of vitamin C and reduced glutathione (GSH; in liver and kidney tissues) of STZ-treated rats. DPDS also caused a marked reduction in the high levels of thiobarbituric acid reactive substances (TBARS) observed in STZ-induced diabetic group. Finally, the inhibition of catalase, delta aminolevulinic acid dehydratase (eth-ALA-D) and isoforms of lactate dehydrogenase (LDH) accompanied by hyperglycemia were prevented by DPDS in all tissues examined. Hence, in comparison with our earlier report, the present findings suggests that, irrespective of the route of administration and the delivery vehicle, DPDS can be considered as an anti-diabetic agent due to its anti-hyperglycemic and antioxidant properties.

Topics: Administration, Oral; Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Blood Glucose; Catalase; Diabetes Mellitus, Experimental; Glutathione; Hypoglycemic Agents; Isoenzymes; L-Lactate Dehydrogenase; Male; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Rats

In the present study, the involvement of glutathione system in the restorative effect of diphenyl diselenide (PhSe)(2) on damage induced by cigarette smoke was investigated. Rat pups were progressively exposed to four, five, and six cigarettes for exposure periods of 15 min during their first, second, and third weeks of life. Thiobarbituric acid reactive species (TBARS) levels, components of the enzymatic antioxidant defenses (superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities), and non-enzymatic antioxidant defenses (vitamin C and non-protein thiol (NPSH) levels) were examined in lungs of pups. The results demonstrated an increase in lipid peroxidation and the alteration in non-enzymatic and enzymatic antioxidant defenses induced by cigarette smoke exposure in lung of pups. Administration of (PhSe)(2) (0.5mg/kg) restored TBARS levels and antioxidant defenses in lungs of rat pups exposed to cigarette smoke. (PhSe)(2) treatment increased NPSH levels and GST activity per se in lungs of rat pups. Together these results indicate that (PhSe)(2) restored oxidative damage induced by cigarette smoke exposure in lungs of rat pups. The glutathione system is involved in antioxidant effect of this compound.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Catalase; Fatty Acids, Monounsaturated; Female; Glutathione; Glutathione Peroxidase; Kinetics; Male; Organoselenium Compounds; Pregnancy; Rapeseed Oil; Rats; Rats, Wistar; Smoke; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Weight Gain

Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4-induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (-ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4.

Topics: Administration, Oral; Alanine Transaminase; Animals; Ascorbic Acid; Aspartate Aminotransferases; Benzene Derivatives; Bilirubin; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Catalase; Creatinine; Drug Synergism; Drug-Related Side Effects and Adverse Reactions; gamma-Glutamyltransferase; Lipid Peroxidation; Liver; Male; Organoselenium Compounds; Porphobilinogen Synthase; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Urea

Oxidative stress has been pointed out as an important molecular mechanism in methylmercury (MeHg) intoxication. At low doses, diphenyl diselenide ((PhSe)2), a structurally simple organoselenium compound, has been shown to possess antioxidant and neuroprotective properties. Here we have examined the possible in vivo protective effect of diphenyl diselenide against the potential pro-oxidative effects of MeHg in mouse liver, kidney, cerebrum and cerebellum. The effects of MeHg exposure (2 mg/(kg day) of methylmercury chloride 10 ml/kg, p.o.), as well as the possible antagonist effect of diphenyl diselenide (1 and 0.4 mg/(kg day); s.c.) on body weight gain and on hepatic, cerebellar, cerebral and renal levels of thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), ascorbic acid content, mercury concentrations and activities of antioxidant enzymes (glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD)) were evaluated after 35 days of treatment. MeHg caused an increase in TBARS and decreased NPSH levels in all tissues. MeHg also induced a decrease in hepatic ascorbic acid content and in renal GPx and CAT activities. Diphenyl diselenide (1 mg/kg) conferred protection against MeHg-induced hepatic and renal lipid peroxidation and at both doses prevented the reduction in hepatic NPSH levels. Diphenyl diselenide also conferred a partial protection against MeHg-induced oxidative stress (TBARS and NPSH) in liver and cerebellum. Of particular importance, diphenyl diselenide decreased the deposition of Hg in cerebrum, cerebellum, kidney and liver. The present results indicate that diphenyl diselenide can protect against some toxic effects of MeHg in mice. This protection may be related to its antioxidant properties and its ability to reduce Hg body burden. We posit that formation of a selenol intermediate, which possesses high nucleophilicity and high affinity for MeHg, accounts for the ability of diphenyl diselenide to ameliorate MeHg-induced toxicity.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Brain; Catalase; Glutathione Peroxidase; Kidney; Lipid Peroxidation; Liver; Male; Mercury; Methylmercury Compounds; Mice; Neuroprotective Agents; Organoselenium Compounds; Oxidative Stress; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Weight Gain

Cigarette smoke exposure has been associated with oxidative stress in several organs. Antioxidant effect of diphenyl diselenide (PhSe)(2), an organoselenium compound, on oxidative damage induced by sub-chronic cigarette smoke exposure in brain and lungs of rats was investigated. Animals were exposed 5 times/week to one, two, three and four cigarettes for exposure periods of 15 min during the first, second, third and fourth weeks. Reactive species (RS) levels, enzymatic antioxidant defenses (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities) and non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol (NPSH) levels) were examined in brain and lungs of rats. An increase in RS levels induced by cigarette smoke in both tissues of rats was demonstrated. Cigarette smoke altered enzymatic antioxidant defenses (GST, CAT and SOD activities) in both tissues, and reduced the non-enzymatic antioxidant defenses in lungs. (PhSe)(2) (0.5 mg/kg/day, 5 times/week) restored RS levels and antioxidant defenses in brain of rats exposed to cigarette smoke. (PhSe)(2) treatment increased NPSH levels, GST and GR activities per se in lungs of rats. In conclusion, sub-chronic exposure to cigarette smoke caused alterations in antioxidant defense system and a tissue-specific oxidative stress in brain and lungs of rats. (PhSe)(2) restored antioxidant defenses in lungs and brain of rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Brain; Glutathione Peroxidase; Glutathione Transferase; Lung; Male; Nicotiana; Organoselenium Compounds; Rats; Rats, Wistar; Smoke; Sulfhydryl Compounds; Superoxide Dismutase

The protective effect of diphenyl diselenide, (PhSe)(2), on oxidative stress induced by cigarette smoke exposure in brains of rat pups was evaluated. Animals were exposed to passive cigarette smoke (15 min/day) in two different experimental protocols: P1 (1, 2, and 3 cigarettes) and P2 (4, 5, and 6 cigarettes) for 3 weeks. Before each period of smoke exposure, animals received an oral administration of (PhSe)(2) (0.5 mg/kg). A number of toxicological parameters in the brain were examined, such as lipid peroxidation, delta-aminolevulinate dehydratase (delta-ALA-D) activity, and components of enzymatic (superoxide dismutase and catalase activities) and non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol levels). In P1, smoke exposure induced an inhibition of catalase activity and an increase of ascorbic acid levels. (PhSe)(2) treatment was able to protect catalase activity but not ascorbic acid levels. In P2, an augmentation of lipid peroxidation, a reduction of enzymatic and non-enzymatic antioxidant status, and an inhibition of delta-ALA-D activity caused by smoke exposure were found. (PhSe)(2) protected the brains of rat pups against oxidative damage induced by smoke exposure. The results are consistent with the antioxidant effect of (PhSe)(2) demonstrated by the reduction of oxidative changes caused by smoke exposure in the brains of pups.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Body Weight; Brain; Brain Diseases; Catalase; Lipid Peroxidation; Magnetic Resonance Spectroscopy; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Rats; Rats, Wistar; Sulfhydryl Compounds; Superoxide Dismutase; Tobacco Smoke Pollution; Weight Gain

Neuronal malfunction is a characteristic feature of diabetic mellitus. Hence, the present study therefore sought to evaluate the effect of diphenyl diselenide (DPDS) on the antioxidant status, sodium pump, cholinergic and glutamatergic system in the rat brain of streptozotocin (STZ) induced diabetes. The results show that although STZ evoke a significant diminution on the antioxidant status and activity of Na(+)/K(+)-ATPase, the activity of acetylcholinesterase and glutamate uptake and release was not altered. However, DPDS was able to markedly restore the observed imbalance in cerebral antioxidant status and also relieve the inhibition of Na(+)/K(+)-ATPase caused by streptozotocin. Hence, we conclude that DPDS is a potential candidate in the management of neuronal dysfunction that often accompanied complications associated with diabetic hyperglycemia.

Topics: Acetylcholinesterase; Animals; Antioxidants; Ascorbic Acid; Behavior, Animal; Benzene Derivatives; Cerebral Cortex; Diabetes Mellitus, Experimental; Glutamic Acid; Glutathione; Male; Organoselenium Compounds; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Streptozocin; Thiobarbituric Acid Reactive Substances

Hypercholesterolaemia and oxidative stress are well-known risk factors in coronary artery diseases. Diphenyl diselenide is a synthetic organoselenium compound that has been shown to have in vitro and in vivo antioxidant properties. In this study, we investigated whether diphenyl diselenide could reduce the hypercholesterolaemia and diminish the tissue oxidative stress in cholesterol-fed rabbits. Twenty-four New Zealand white male rabbits were randomly divided into four groups. Each group was fed a different diet as follows: Control group--regular chow; Cholesterol group--1% cholesterol-enriched diet; diphenyl diselenide group--regular diet supplemented with 10 ppm diphenyl diselenide; and Chol/diphenyl diselenide group--the same cholesterol-rich supplemented with 10 ppm diphenyl diselenide. After 45 days of treatment, the rabbits were killed and the blood, liver, and brain were used for laboratory analysis. The results showed that the serum levels of total cholesterol were markedly increased in cholesterol-fed rabbits and the consumption of diphenyl diselenide decreased these levels approximately twofold in Chol/diphenyl diselenide rabbits (P < 0.05). The intake of diphenyl diselenide by hypercholesterolaemic rabbits diminished the serum and hepatic thiobarbituric acid reactive substances levels as well as the production of reactive oxygen species in the blood and brain (P < 0.05) when compared to the cholesterol group. In addition, diphenyl diselenide supplementation increased hepatic and cerebral delta-aminolevulinic dehydratase activity and hepatic non-protein thiol groups levels despite hypercholesterolaemia (P < 0.05). In summary, the results showed that diphenyl diselenide reduced the hypercholesterolaemia and the oxidative stress in cholesterol-fed rabbits.

Topics: Animal Feed; Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Brain; Brain Chemistry; Cholesterol; Cholesterol, Dietary; Hypercholesterolemia; Liver; Male; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Rabbits; Random Allocation; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Triglycerides

This study was designed to examine if diphenyl diselenide (PhSe)(2), an organoselenium compound, attenuates oxidative stress caused by acute physical exercise in skeletal muscle and lungs of mice. Swiss mice were pre-treated with (PhSe)(2) (5 mg kg(-1) day(-1)) for 7 days. At the 7th day, the animals were submitted to acute physical exercise which consisted of continuous swimming for 20 min. The animals were euthanized 1 and 24 h after the exercise test. The levels of thiobarbituric acid reactive species (TBARS), non-protein thiols (NPSH) and ascorbic acid and the activity of catalase (CAT) were measured in the lungs and skeletal muscle of mice. Glycogen content was determined in the skeletal muscle of mice. Parameters in plasma (urea and creatinine) were determined. The results demonstrated an increase in TBARS levels induced by acute physical exercise in the skeletal muscle and lungs of mice. Animals submitted to exercise showed an increase in non-enzymatic antioxidant defenses (NPSH and ascorbic acid) in the skeletal muscle. In lungs of mice, activity of CAT was increased. (PhSe)(2) protected against the increase in TBARS levels and ameliorated antioxidant defenses in the skeletal muscle and lungs of mice submitted to physical exercise. These results indicate that acute physical exercise caused a tissue-specific oxidative stress in the skeletal muscle and lungs of mice. (PhSe)(2) protected against oxidative damage induced by acute physical exercise in mice.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Catalase; Creatinine; Glycogen; Lung; Male; Mice; Muscle, Skeletal; Organoselenium Compounds; Oxidative Stress; Physical Conditioning, Animal; Thiobarbiturates; Urea

The effect of combined therapy with diphenyl diselenide (PhSe)(2) and sodium 2,3-dimercapto-propane-1-sulphonate (DMPS) against alterations induced by mercury (Hg(2+)) was evaluated. Mice were exposed to mercuric chloride (HgCl(2)) (1mg/kg, subcutaneously) for two weeks. After that, mice received (PhSe)(2) (15.6 mg/kg), or DMPS (12.6 mg/kg), or a combination of both for one week. Thiobarbituric acid-reactive substances (TBARS), ascorbic acid and Hg(2+) levels and glutathione S-transferase (GST) and catalase (CAT) activities were carried out in kidney. Hematological parameters, plasmatic bilirubin, uric acid, urea and creatinine levels as well as lactate dehydrogenase (LDH) activity were determined. (PhSe)(2) or DMPS restored the increase in LDH activity and TBARS, bilirubin, uric acid, urea and creatinine levels caused by HgCl(2). The levels of erythrocytes, hemoglobin and hematocrit reduced by HgCl(2) exposure were restored by (PhSe)(2) or DMPS administration in mice. Leukocyte and platelet counts modified by HgCl(2) exposure were restored by (PhSe)(2) or DMPS therapy. DMPS restored the increase in Hg(2+) levels induced by exposure to HgCl(2). Concomitant administration of (PhSe)(2) and DMPS reduced the effectiveness of DMPS in restoring damage induced by HgCl(2). Combined therapy with (PhSe)(2) and DMPS was less effective than isolated therapies in restoring the damage induced by HgCl(2) in mice.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Bilirubin; Blood Cell Count; Catalase; Chelating Agents; Creatinine; Drug Interactions; Drug Therapy, Combination; Glutathione Transferase; Hemoglobins; Leukocyte Count; Lymphocytes; Male; Mercuric Chloride; Mice; Monocytes; Neutrophils; Organoselenium Compounds; Platelet Count; Thiobarbituric Acid Reactive Substances; Unithiol; Uric Acid

In this study we evaluated the effect of diphenyl diselenide (PhSe)(2) on glycerol-induced acute renal failure in rats. Rats were pre-treated by gavage every day with (PhSe)(2 )(7.14 mg kg(-1)) for 7 days. On the eighth day, rats received an intramuscular injection of glycerol (8 mL kg(-1)). Twenty-four hours afterwards, rats were euthanized and the levels of urea and creatinine were measured in plasma. Catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), delta-aminolevulinate dehydratase (delta-ALA-D) and Na(+), K(+)-ATPase activities and ascorbic acid levels were evaluated in renal homogenates. Histopathological evaluations were also performed. The results demonstrated that (PhSe)(2) was able to protect against the increase in urea and creatinine levels and histological alterations in kidney induced by glycerol. (PhSe)(2) protected against the inhibition in delta-ALA-D, CAT and GPx activities and the reduction in ascorbic acid levels induced by glycerol in kidneys of rats. In conclusion, the present results indicate that (PhSe)(2) was effective in protecting against acute renal failure induced by glycerol.

Topics: Animals; Ascorbic Acid; Benzene Derivatives; Catalase; Creatinine; Drug Interactions; Glutathione Peroxidase; Glutathione Transferase; Glycerol; Kidney; Male; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Urea

The involvement of non-enzymatic antioxidant defenses in the protective effect of diphenyl diselenide (PhSe)(2) on testicular damage caused by cadmium in mice was investigated. Mice received a single dose of CdCl(2) (5mg/kg, intraperitoneally). Thirty minutes after the CdCl(2) injection, they received a single oral dose of (PhSe)(2) (400micromol/kg). Twenty-four hours after CdCl(2) administration, blood samples were collected and mice were killed and had their testes dissected. Parameters in plasma (aspartate (AST) and alanine (ALT) aminotransferases and lactato dehydrogenase (LDH) activities as well as creatinine levels) were determined. The activity of delta-aminolevulinate dehydratase (delta-ALA-D), the levels of thiobarbituric acid-reactive substances (TBARS), ascorbic acid and nonprotein thiols (NPSH) and histological analysis were determined in collected samples. Results demonstrated that (PhSe)(2) protected against toxicity induced by CdCl(2) on delta-ALA-D activity, ascorbic acid and NPSH levels. (PhSe)(2) protected against the increase in plasma AST, ALT and LDH activities caused by CdCl(2). Testes of mice exposed to CdCl(2) showed marked histopathological alterations that were ameliorated by administration of (PhSe)(2). (PhSe)(2) protected against toxicity induced by CdCl(2) in testes of mice. Ascorbic acid and NPSH, non-enzymatic antioxidant defenses, are involved in the protective effect of (PhSe)(2) against testicular damage caused by CdCl(2) in mice.

Topics: Analysis of Variance; Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Cadmium; Cadmium Chloride; Clinical Enzyme Tests; Creatinine; Injections, Intraperitoneal; Lipid Peroxidation; Male; Mice; Organ Size; Organoselenium Compounds; Porphobilinogen Synthase; Seminiferous Tubules; Sulfhydryl Compounds; Testicular Diseases; Testis

The aim of the present study was to evaluate if diphenyl diselenide administered by oral route was effective in restoring gastric lesions induced by ethanol. The possible involvement of oxidative stress in diphenyl diselenide antiulcer effect was also evaluated. Different doses of diphenyl diselenide (dissolved in soya bean oil, 1mL/kg) were administered orally 1h before (pre-treatment study) or 1h after ethanol (70%, v/v, 2mL/kg, post-treatment study). Ulcer lesions were quantified 1h after ethanol administration (pre-treatment protocol) or 1h after diphenyl diselenide study (post-treatment protocol). Diphenyl diselenide (0.1-10mg/kg or 0.32-32micromol/kg), when administered previously or posteriorly prevented and reversed respectively, the development of gastric lesions induced by ethanol in rats. A number of markers of oxidative stress were examined in rat stomach including thiobarbituric acid reactive species (TBARS), catalase (CAT), superoxide dismutase (SOD), non-protein thiol groups (NPSH) and ascorbic acid. In addition to attenuating the gastric lesions, low doses of diphenyl diselenide prevented (pre-treatment) or reversed (post-treatment) the ethanol-induced changes in TBARS, SOD activity and ascorbic acid content. In conclusion, the present data reveal that diphenyl diselenide, administered by oral route, possesses an antiulcer effect by modulating antioxidant mechanisms.

Topics: Animals; Anti-Ulcer Agents; Ascorbic Acid; Benzene Derivatives; Catalase; Ethanol; Intestinal Mucosa; Lipid Peroxidation; Magnetic Resonance Spectroscopy; Male; Organoselenium Compounds; Oxidative Stress; Rats; Rats, Wistar; Stomach Ulcer; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Cadmium is an environmental toxic metal implicated in human diseases. In the present study, the effect of diphenyl diselenide, (PhSe)(2), on sub-chronic exposure with cadmium chloride (CdCl(2)) was investigated in rats. Male adult Swiss albino rats received CdCl(2) (10 micromol/kg, orally) and (PhSe)(2) (5 micromol/kg, orally) for a period of 30 days. A number of parameters were examined as indicators of toxicity, including hepatic and renal damage, glucose and glycogen levels and markers of oxidative stress. Cadmium content, liver histology, delta-aminolevulinate dehydratase (delta-ALA-D) activity, metallothionein (MT) levels were also evaluated. Cadmium content determined in the tissue of rats exposed to CdCl(2) provides evidence that the liver is the major cadmium target where (PhSe)(2) acts. The concentration of cadmium in liver was about three fold higher than that in kidney, and (PhSe)(2) reduced about six fold the levels of this metal in liver of rats exposed. Rats exposed to CdCl(2) showed histological alterations abolished by (PhSe)(2) administration. (PhSe)(2) administration ameliorated plasma malondialdehyde (MDA) levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) activities increased by CdCl(2) exposure. Urea and bilirubin levels increased by CdCl(2) exposure were also reduced by (PhSe)(2). In conclusion, this study demonstrated that co-treatment with (PhSe)(2) ameliorated hepatotoxicity and cellular damage in rat liver after sub-chronic exposure with CdCl(2). The proposed mechanisms by which (PhSe)(2) acts in this experimental protocol are its antioxidant properties and its capacity to form a complex with cadmium.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Benzene Derivatives; Bilirubin; Blood Glucose; Cadmium; Cadmium Chloride; Chemical and Drug Induced Liver Injury; gamma-Glutamyltransferase; Glycogen; Kidney; L-Lactate Dehydrogenase; Liver; Liver Diseases; Male; Malondialdehyde; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Rats; Rats, Wistar; Sulfhydryl Compounds

The effect of dietary diphenyl diselenide (1 ppm) on N-nitroso-N-methylurea (NMU)-induced mammary carcinogenesis was examined in female Wistar rats. Beginning at 5 weeks of age, the animals were fed with either control or diphenyl-diselenide-supplied diets until the end of the study (210 days). At 50 days of age, mammary tumor was induced by the administration of three doses of NMU (50 mg/kg body wt, intraperitoneally) once a week for 3 weeks. In experimental trials, latency to tumor onset was extended in rats fed with diet supplemented with diphenyl diselenide (P < 0.05). The incidence and frequency of tumors were significantly small in animals supplemented with diphenyl diselenide. However, the multiplicity of tumors was not altered by dietary diphenyl diselenide. Diphenyl diselenide supplementation also restored superoxide dismutase (SOD) activity and vitamin C levels altered in the NMU group (P < 0.05). Our results suggest that diphenyl diselenide can be considered a chemopreventive agent, even when supplemented at a relatively low concentration.

Topics: Animals; Anticarcinogenic Agents; Ascorbic Acid; Benzene Derivatives; Biomarkers; Body Weight; Carcinogens; Comet Assay; Diet; Female; Lipid Peroxidation; Liver; Mammary Neoplasms, Animal; Methylnitrosourea; Neoplasm Proteins; Organ Size; Organoselenium Compounds; Rats; Rats, Wistar; Superoxide Dismutase

The effect of cigarette smoke exposure on lungs of rat pups was evaluated. Animals were exposed to passive cigarette smoke during 3 weeks and a number of toxicological parameters in lung of pups were examined, such as lipid peroxidation, delta-aminolevulic acid dehydratase (delta-ALA-D) activity, components of the enzymatic antioxidant defenses (superoxide dismutase (SOD) and catalase activities) and non-enzymatic antioxidant defenses (Vitamin C and non-protein thiol (NPSH) levels). Furthermore, a possible protective effect of diphenyl diselenide, (PhSe)(2), was studied. The results demonstrated an increase in lipid peroxidation, an inhibition of delta-ALA-D activity, a reduction of Vitamin C and NPSH levels induced by cigarette smoke exposure, indicating damage in lungs of rat pups. Oral administration of (PhSe)(2) (0.5mg/kg) restored TBARS levels, non-enzymatic antioxidant defenses and activity of delta-ALA-D. These results indicated that exposure to cigarette smoke enhanced oxidative stress, thereby disturbing the tissue defense system. (PhSe)(2) protected against oxidative damage induced by cigarette smoke exposure in lung of rat pups.

Topics: Aminolevulinic Acid; Animals; Animals, Suckling; Antioxidants; Ascorbic Acid; Benzene Derivatives; Body Weight; Catalase; Female; Lipid Peroxidation; Lung Diseases; Male; Organoselenium Compounds; Pregnancy; Rats; Rats, Wistar; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Tobacco Smoke Pollution

The effect of cadmium (Cd(2+)) on delta-aminolevulinate dehydratase (delta-ALA-D) activity from rat lung in vitro was investigated. delta-ALA-D activity, a parameter for metal intoxication, has been reported as a target of Cd(2+) in different tissues. The protective effect of monotherapies with dithiol chelating (meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS)) or antioxidant agents (ascorbic acid, diphenyl diselenide (PhSe)(2), and N-acetylcysteine (NAC)) was evaluated. The effect of a combined therapy (dithiol chelatingxantioxidant agent) was also studied. Zinc chloride (ZnCl(2)) and dithiothreitol (DTT) were used to investigate the mechanisms involved in cadmium, chelating and antioxidant effects on delta-ALA-D activity. Cadmium inhibited rat lung delta-ALA-D activity at low concentrations. DTT (3mM), but not ZnCl(2) (100microM), protected the inhibition of enzyme activity caused by Cd(2+). Chelating agents were not effective in restoring the enzyme activity. DMPS and DMSA presented inhibitory effect on enzyme activity. DTT restored the inhibition caused by both chelating agents, but ZnCl(2) restored only the inhibitory effect induced by DMSA. These compounds caused a marked potentiation of delta-ALA-D inhibition induced by Cd(2+). ZnCl(2) did not restore inhibition of enzyme activity caused by Cd(2+) plus chelating agents. Conversely, DTT restored the inhibition induced by Cd(2+)/DMSA, but not by Cd(2+)/DMPS. Antioxidants were not effective in ameliorating delta-ALA-D inhibition induced by Cd(2+), whereas ascorbic acid potentiated the enzyme inhibition induced by this metal. A combined effect of Cd(2+)xDMPSx(PhSe)(2) and Cd(2+)xDMPSxNAC was observed. There was no combined effect of Cd(2+)xchelatorxantioxidants when DMSA was used. This study demonstrated that Cd(2+)inhibited delta-ALA-D activity and chelating and antioxidant agents, alone or combined, did not restore the enzyme activity. In contrast, these compounds potentiated the inhibition induced by Cd(2+) in rat lung.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Cadmium Chloride; Chelating Agents; Chlorides; Dithiothreitol; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Environmental Pollutants; Enzyme Inhibitors; Lung; Male; Organoselenium Compounds; Porphobilinogen Synthase; Rats; Rats, Wistar; Succimer; Unithiol; Zinc Compounds

Selenium compounds, like diphenyl diselenide (Ph(2)Se(2)), possess glutathione peroxidase (GSHPx)-like activities and other antioxidant properties. The aim of this study was to evaluate the effects of a long-term oral supplementation with Ph(2)Se(2) on various toxicological parameters in rabbits. Adult New Zealand male rabbits were divided into four groups: Group I served as control; Groups II, III and IV received 0.3, 3.0 and 30 p.p.m. of Ph(2)Se(2) pulverized in the chow for 8 months. A number of toxicological parameters were examined in liver, kidney, cerebral cortex and hippocampus, such as delta-aminolaevulinic acid dehydratase (delta-ALA-D), catalase (CAT), GSHPx activities, non-protein thiol (-SH), lipid peroxidation and ascorbic acid levels. The results indicated that supplementation 30 p.p.m. Ph(2)Se(2 )significantly increased delta-ALA-D activity in liver and in cerebral cortex. Non-protein -SH levels were significantly increased in liver but not in kidney, cerebral cortex and hippocampus of rabbits. Ascorbic acid content was significantly lower in the liver and cerebral cortex after supplementation with 30 p.p.m. Ph(2)Se(2). Conversely, no alterations in GSHPx and CAT activities, nor in thiobarbituric acid reactive substances levels were observed in rabbit tissues. These results indicate that oral supplementation with Ph(2)Se(2) is relatively secure in rabbits after 8 months of exposure. The findings encourage further experiments on the potential therapeutic effects of such compound.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Brain; Catalase; Dose-Response Relationship, Drug; Glutathione Peroxidase; Kidney; Lipid Peroxidation; Liver; Male; Organoselenium Compounds; Porphobilinogen Synthase; Rabbits; Thiobarbituric Acid Reactive Substances; Time Factors

This study was designed to examine if diphenyl diselenide (PhSe)(2), an organoselenium compound, attenuates pulmonar and cerebral oxidative stress caused by sub-chronic exposure to CdCl(2). Male adult Swiss albino mice received CdCl(2) (10 micromol/kg, subcutaneously), 5 times/week, for 4 weeks. (PhSe)(2) (10 micromol/kg or 20 micromol/kg, orally) was given concomitantly with CdCl(2) to mice. A number of toxicological parameters in lung and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D), superoxide dismutase (SOD) and catalase activities, lipid peroxidation, non-protein thiols (NPSH) and ascorbic acid content. Na(+),K(+)-ATPase activity, acetylcholinesterase (AChE) activity, [(3)H]glutamate uptake and [(3)H]glutamate release were also carried out in brain. Cadmium concentration and histopathological analysis were carried out in lung tissue. (PhSe)(2) at the dose of 20 micromol/kg protected the inhibition of delta-ALA-D, SOD and CAT activities, the reduction of vitamin C content and the increase of lipid peroxidation levels caused by CdCl(2) in lungs. At 10 micromol/kg, (PhSe)(2) protected cerebral AChE and CAT activities inhibited by CdCl(2). There were no histopathological alterations in the lung of mice after CdCl(2) exposure. The pulmonary cadmium concentration was higher (2.8-fold) in the group exposed to CdCl(2) than in control mice. (PhSe)(2) at dose of 20 micromol/kg reduced cadmium concentration towards the control level. The results suggest that oral administration of (PhSe)(2) attenuated the oxidative damage induced by CdCl(2) in lung and brain of mice.

Topics: Acetylcholinesterase; Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Brain; Brain Diseases; Cadmium Chloride; Catalase; Disease Models, Animal; Dose-Response Relationship, Drug; Glutamic Acid; Lipid Peroxidation; Lung; Lung Diseases; Male; Mice; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Sodium-Potassium-Exchanging ATPase; Sulfhydryl Compounds; Superoxide Dismutase

The present study was conducted to evaluate the toxicity of the exposure to diphenyl diselenide [(PhSe)2] and diphenyl ditelluride [(PhTe)2] on reproductive system in Wistar rats. Adult male rats were exposed intraperitonealy (acute) or subcutaneously (sub-chronic, during 4 or 8 weeks) to (PhSe)2 or (PhTe)2 prior to mating. A number of biochemical parameters in rat testes were examined, such as delta-aminolevulinate dehydratase (delta-ALA-D) activity, lipid peroxidation, glycogen content and components of the antioxidant defenses (superoxide dismutase (SOD) activity and ascorbic acid concentration). Furthermore, a possible effect on fertility and reproductive performance in male rats were studied. Sperm counts of caudal epididymis were also evaluated. No lethality was noted in any group. Reduction on body weight in rats which received (PhTe)2 was only evidenced in acute exposure, while (PhSe)2-exposed rats presented significant loss of body weight in acute and 4 week-exposure. Mating and fertility indexes were not affected after acute and sub-chronic exposure. Regarding other parameters studied, except for a decrease in testes glycogen content in acutely (PhSe)2-treated group, no alterations were found in treated groups. Sperm counts of rats treated acutely and sub-chronically were unaffected by drugs exposure. Histological evaluation revealed no modification on testicular tissue in rats exposed to (PhSe)2 and (PhTe)2. The results suggest the absence of the male reproductive toxicity induced by (PhSe)2 and (PhTe)2 administered intraperitonealy (acute) or subcutaneously (sub-chronical) to adult rats Wistar.

Topics: Animals; Ascorbic Acid; Benzene Derivatives; Body Weight; Female; Fertility; Glycogen; Injections, Intraperitoneal; Injections, Subcutaneous; Lipid Peroxidation; Male; Organometallic Compounds; Organoselenium Compounds; Porphobilinogen Synthase; Pregnancy; Rats; Rats, Wistar; Reproduction; Sperm Count; Superoxide Dismutase; Testis; Thiobarbituric Acid Reactive Substances; Toxicity Tests, Acute; Toxicity Tests, Chronic

The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. The present study was conducted to evaluate the potential toxicity of long time oral exposure to diphenyl diselenide (PhSe)2 in rabbits. Male adult New Zealand rabbits were divided into four groups, group I served as control; groups II, III and IV received 0.3, 3.0 and 30 ppm of (PhSe)2 pulverized in the chow for 8 months. A number of parameters were examined in blood as indicators of toxicity, including delta-aminolevulinate dehydratase (delta-ALA-D), catalase, glutathione peroxidase (GPx), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine, TBARS, non-protein-SH, ascorbic acid and selenium. The results demonstrated that 6 and 8 months of 30 ppm (PhSe)2 intake caused a significant increase in blood delta-ALA-D activity. Erythrocyte non-protein thiol levels were significantly increased after 2 months of 30 ppm (PhSe)2 intake and then return to control levels after prolonged periods of intake. Ingestion of 3.0 ppm of (PhSe)2 for 8 months significantly increased catalase activity in erythrocytes. Conversely, no alterations in GPx, ALT, AST, TBARS and selenium levels were observed in rabbit serum, conversely, selenium levels in peri-renal adipose tissue were significantly increased after 8 months of 30 ppm (PhSe)2 intake, indicating its great lipophylicity. The present results suggest that diphenyl diselenide was not hepato- or renotoxic for rabbits, but caused some biochemical alterations that can be related to some pro-oxidant activity of the compound (particularly the reduction in Vitamin C).

Topics: Administration, Oral; Animal Feed; Animals; Ascorbic Acid; Benzene Derivatives; Blood; Body Weight; Catalase; Creatinine; Glutathione Peroxidase; Male; Molecular Structure; Organoselenium Compounds; Porphobilinogen Synthase; Rabbits; Selenium; Sulfhydryl Compounds; Thiobarbituric Acid Reactive Substances; Time Factors

This study was designed to determine the effect of diphenyl diselenide and ebselen, synthetic organoselenium compounds with antioxidant properties, in diabetic rats. Diabetes was induced by the administration of streptozotocin (STZ) (45mg/kg, intravenous). In experimental trials, diphenyl diselenide, but not ebselen, caused a significant reduction in blood glucose levels of STZ-treated rats. This effect of diphenyl diselenide was accompanied by a reduction in the levels of glycated proteins. Diphenyl diselenide ameliorate superoxide dismutase activity (liver and erythrocytes) and Vitamin C levels (liver, kidney and blood), which were decreased in STZ-treated rats. In normal rats, diphenyl diselenide caused per se an increase in hepatic, renal and blood GSH levels. Similarly, treatment with diphenyl diselenide restored hepatic and renal GSH levels in STZ-treated rats. TBARS and protein carbonyl levels were not modified by STZ and/or diphenyl diselenide and ebselen treatments. Our findings suggest that diphenyl diselenide can be considered an anti-diabetogenic agent by exhibiting anti-hyperglycemic and antioxidant properties.

Topics: Alanine Transaminase; Aminolevulinic Acid; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Azoles; Benzene Derivatives; Blood Glucose; Diabetes Mellitus, Experimental; Fructosamine; Glutathione; Glycated Hemoglobin; Hyperglycemia; Isoindoles; L-Lactate Dehydrogenase; Liver; Male; Organoselenium Compounds; Oxidative Stress; Random Allocation; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Superoxide Dismutase

The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. In the present investigation subchronic deleterious effects of cadmium-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 (5 micromol/kg) were studied. Male adult Swiss albino mice (25-35 g) received CdCl2 (10 micromol/kg, subcutaneously), five times/week, for 4 weeks. A number of toxicological parameters in blood, liver, kidney, spleen and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation and ascorbic acid content, the parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and lactate dehydrogenase (LDH) were also determined. The results demonstrated that cadmium caused inhibition of delta-ALA-D activity in liver (24%), kidney (33%) and spleen (73%) and (PhSe)2 therapy was effective in restoring enzyme activity in all tissues. A reduction in ascorbic acid content was observed in kidney (11%) and spleen (10.7%) of cadmium-treated mice and (PhSe)2 was only effective in improving this reduction in kidney. An increase of lipid peroxidation induced by cadmium was noted in liver (29%) and brain (28%) tissues and (PhSe)2 therapy was effective in restoring TBARS levels in both tissues. We also observed an increase on plasma LDH (1.99-times), AST (1.93-times) and ALT (4.24-times) activities. (PhSe)2 therapy was effective in restoring AST activity at control level. (PhSe)2 did not present toxic effects when plasma parameters were evaluated. The results suggest that the administration of an antioxidant (PhSe)2, during cadmium intoxication may provide beneficial effects by reducing oxidative stress in tissues.

Topics: Alanine Transaminase; Animals; Ascorbic Acid; Aspartate Aminotransferases; Benzene Derivatives; Brain; Cadmium; Creatinine; Kidney; L-Lactate Dehydrogenase; Lipid Peroxidation; Liver; Male; Mice; Organoselenium Compounds; Oxidative Stress; Spleen; Urea

The deleterious effect of acute cadmium-intoxication in mice testes was evaluated. Animals received a single dose of CdCl2 (2.5 or 5 mg/kg, intraperitoneally) and a number of toxicological parameters in mice testes were examined, such as delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation, hemoglobin and ascorbic acid contents. Furthermore, the parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were also determined. Thus, a possible protective effect of 2,3-dimercapto-1-propane-sulfonic acid (DMPS) and diphenyl diselenide (PhSe)2 were studied. The results demonstrated an inhibition of delta-ALA-D activity, a reduction of ascorbic acid and an increase of lipid peroxidation induced by cadmium, indicating testes damage. Furthermore, we observed an increase of plasma LDH, AST and ALT activities. DMPS (400 mol/kg) and (PhSe)2 (100 micromol/kg) partially protected from the inhibitory effect of 2.5 mg/kg CdCl2 on delta-ALA-D and from the increase of TBARS (thiobarbituric acid reactive species) levels. (PhSe)2 therapy was effective in ameliorate ascorbic acid content when the cadmium dose was 2.5 mg/kg. Treatment with DMPS and (PhSe)2, individually or combined, was inefficient in reducing cadmium-induced plasma LDH and ALT activity increase. The use of combined therapy (DMPS plus (PhSe)2) proved to be efficient in decreasing cadmium levels in testes and in ameliorating plasma AST activity from animals that received the highest dose of cadmium.

Topics: Alanine Transaminase; Analysis of Variance; Animals; Antidotes; Ascorbic Acid; Aspartate Aminotransferases; Benzene Derivatives; Cadmium; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hemoglobins; Injections, Intraperitoneal; L-Lactate Dehydrogenase; Lipid Peroxidation; Male; Mice; Organoselenium Compounds; Oxidation-Reduction; Oxidative Stress; Porphobilinogen Synthase; Testis; Thiobarbituric Acid Reactive Substances; Treatment Outcome; Unithiol

Sodium selenite (Na2SeO3) is the selenium form used in the composition of dietary supplements, and diphenyl diselenide (PhSe)2 is an important intermediate in organic synthesis, which increases the risk of human exposure to this chemical in the workplace. These compounds have been reported to inhibit the cerebral and hepatic aminolevulinic acid dehydratase (ALA-D) in vitro, and now we show that ascorbic acid can reverse some alterations caused by in vivo selenium exposure, but not ALA-D inhibition. The effect of Na2SeO3 or (PhSe)2 and ascorbic acid on selenium distribution, total non-protein thiol, ascorbic acid content (liver and brain) and haemoglobin was also examined. Mice were exposed to 250 micromol/kg (PhSe)2, or 18.75 micromol/kg Na2SeO3 subcutaneously, and to ascorbic acid, twice a day, 1 mmol/kg intraperitonially, for 10 days. Hepatic ALA-D of mice treated with (PhSe)2 was inhibited about 58% and similar results were observed in the animals that received ascorbic acid supplementation (P<0.01, for (PhSe)2-treated and (PhSe)2+ascorbic acid-treated mice). The haemoglobin content decreased after treatment with (PhSe)2 (P<0.01). However, the haemoglobin content of the (PhSe)2+ascorbic acid group was significantly higher than in the (PhSe)2-treated mice (P<0.05), and similar to control (P>0.10). Ascorbic acid treatment decreased significantly the hepatic and cerebral deposition of Se in (PhSe)2-exposed mice (P<0.01). Hepatic non-protein thiol content was not changed by treatment with (PhSe)2, ascorbic acid or (PhSe)2+ascorbic acid. Hepatic content of ascorbic acid was twice that in mice that received (PhSe)2, independent of ascorbic acid treatment (P<0.001). The results of this study suggest that vitamin C may have a protective role in organodiselenide intoxication.

Topics: Animals; Ascorbic Acid; Benzene Derivatives; Brain; Liver; Male; Mice; Occupational Diseases; Organoselenium Compounds; Selenium; Selenium Compounds; Selenium Oxides; Soil Pollutants