naphthoquinones and Body-Weight

The combination antimalarial therapy of artemisinin-naphthoquine (ART-NQ) was developed as a single-dose therapy, aiming to improve adherence relative to the multiday schedules of other artemisinin combination therapies. The pharmacokinetics of ART-NQ has not been well characterized, especially in children. A pharmacokinetic study was conducted in adults and children over 5 years of age (6 to 10, 11 to 17, and ≥18 years of age) with uncomplicated malaria in Tanzania. The median weights for the three age groups were 20, 37.5, and 55 kg, respectively. Twenty-nine patients received single doses of 20 mg/kg of body weight for artemisinin and 8 mg/kg for naphthoquine, and plasma drug concentrations were assessed at 13 time points over 42 days from treatment. We used nonlinear mixed-effects modeling to interpret the data, and allometric scaling was employed to adjust for the effect of body size. The pharmacokinetics of artemisinin was best described by one-compartment model and that of naphthoquine by a two-compartment disposition model. Clearance values for a typical patient (55-kg body weight and 44.3-kg fat-free mass) were estimated as 66.7 L/h (95% confidence interval [CI], 57.3 to 78.5 L/h) for artemisinin and 44.2 L/h (95% CI, 37.9 to 50.6 L/h) for naphthoquine. Nevertheless, we show via simulation that patients weighing ≥70 kg achieve on average a 30% lower day 7 concentration compared to a 48-kg reference patient at the doses tested, suggesting dose increases may be warranted to ensure adequate exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT01930331.).

Topics: 1-Naphthylamine; Adolescent; Adult; Aminoquinolines; Antimalarials; Artemisinins; Body Weight; Child; Folic Acid Antagonists; Humans; Malaria, Falciparum; Naphthoquinones; Tanzania

A novel series of 4-substituted-3,4-dihydrobenzo[h]quinoline-2,5,6(1H)-triones as NQO1-directed antitumor agents were designed, synthesized, biologically evaluated. Compounds 3n, 3o and 3j proved to be good NQO1 substrates that showed increased metabolic rates relative to that of β-lapachone. In addition, 3n, 3o and 3j potently inhibited the growth of NQO1-rich breast cancer MCF-7 cell, liver hepatocellular HepG2 cell, and lung cancer A549 cell. In cellular mechanistic studies, the representative compound 3o triggered ROS generation depending on the NQO1 dose, and induce HepG2 cell apoptosis by the generated oxidative stress. In HepG2 xenografts mouse model, at the dose of 20 mg/kg, 3o remarkably suppressed the tumor growth without affecting the animal weights.

Topics: Animals; Antineoplastic Agents; Apoptosis; Body Weight; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Heterografts; Humans; Mice; Models, Molecular; Molecular Targeted Therapy; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Neoplasms, Experimental; Oxidative Stress; Quinolines; Reactive Oxygen Species; Structure-Activity Relationship

In this study, we aim to investigate whether shikonin prevents against NAFLD. After feeding high-fat diet (HFD) for 10 weeks, Sprague-Dawley rats were received different doses of shikonin (5mg/kg/day, 10mg/kg/day and 20mg/kg/day) by gavage for the last 12 weeks of a total of 22 weeks of a HFD. Our results showed that total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase were significantly increased, while high-density lipoprotein cholesterol was decrease, accompanied by hepatic injury and lipid accumulation in HFD-fed rats. Shikonin treatment attenuated the above biochemical and histopathological changes. Similarly, HFD-induced the increase of hepatic TC and TG levels were also ameliorated by shikonin treatment. Furthermore, shikonin observably mitigated HFD-induced the liver fibrosis and the increase of plasminogen activator inhibitor type 1, connective tissue growth factor, collagen III and IV expression. Additionally, shikonin markedly inhibited HFD-induced the decrease of proliferator-activated receptor γ (PPARγ) and matrix metalloproteinases-9 (MMP-9) expression and the increase of tissue inhibitor of metalloproteinases-1 (TIMP-1) expression in liver tissue. This study demonstrates that shikonin ameliorates hepatic lipid dysregulation and fibrosis through PPARγ and MMP-9/TIMP-1 axis, suggesting that shikonin may be a potential therapeutic agent for the treatment of NAFLD.

Topics: Animals; Body Weight; Boraginaceae; Diet, High-Fat; Gene Expression Regulation; Lipid Metabolism; Liver; Liver Cirrhosis; Male; Matrix Metalloproteinase 9; Naphthoquinones; Non-alcoholic Fatty Liver Disease; Plants, Medicinal; PPAR gamma; Rats, Sprague-Dawley; Tissue Inhibitor of Metalloproteinase-1

Rhinacanthus nasutus has traditionally been used in the treatment of various disorders including diabetes mellitus. Rhinacanthins-rich extract (RRE) is a semipurified R. nasutus leaf extract that contains 60% w/w of rhinacanthin-C (RC) obtained by a green extraction process. The purpose of this study was to investigate the anti-hyperglycemic and anti-hyperlipidemic activity of RRE (15 mg/kg equivalent to RC content) in comparison to its marker compound RC (15 mg/kg) and the standard drug glibenclamide (Glb) (600 μg/kg) in nicotinamide-streptozotocin induced diabetic rats for 28 days. In addition, the in silico pharmacokinetic and toxicity analysis of RC was also performed. RRE, RC and Glb significantly reduced the FBG, HbA1c and food/water intake while increasing the insulin level and body weight in diabetic rats without affecting the normal rats. The serum lipid, liver and kidney biomarkers were markedly normalized by RRE, RC and Glb in diabetic rats without affecting the normal rats. Moreover, the histopathology of the pancreas revealed that RRE, RC and Glb evidently restored the islets of Langerhans in diabetic rats. The overall results indicated that RRE has equivalent antidiabetic potential to that of RC. Moreover, the in silico pharmacokinetic and toxicity analysis predicts that RC is orally non-toxic, non-carcinogenic and non-mutagenic with a decent bioavailability. The undertaken study suggests that RRE could be used as an effective natural remedy in the treatment of diabetes.

Topics: Acanthaceae; Animals; Body Weight; Computer Simulation; Diabetes Mellitus, Experimental; Eating; Glycated Hemoglobin; Green Chemistry Technology; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Lipid Metabolism; Male; Naphthoquinones; Niacinamide; Pancreas; Plant Extracts; Plant Leaves; Rats, Wistar; Streptozocin

Our previous studies have shown that plumbagin effectively inhibits hepatic stellate cell (HSC) proliferation. Thus, plumbagin-mediated anti-fibrotic effects in vivo merit further investigation.. We used rat models to assess the potential benefits of plumbagin against CCl₄-induced liver fibrosis.. The results showed that plumbagin lowered the serum concentrations of liver functional enzymes (ALT, AST, ALB, TBIL) in CCl₄-fibrotic rats while reducing inflammatory cytokine levels (IL-6, TNF-α). As reflected in pathological examinations, rats that were administered plumbagin showed decreased collagen markers (HA, LN, PCIII and CIV) in liver tissues and improved hepatocellular impairments. In addition, plumbagin contributed to down-regulating NF-κB and TLR-4 mRNA in CCl₄-lesioned livers. As revealed in the immunohistochemical assay, plumbagin-administered rats showed reduced levels of α-SMA and TNF-α immunoreactive cells in liver tissue.. Collectively, these findings offer appealing evidence that plumbagin may serve as an anti-fibrotic medication through inactivating the NF-κB/TLR-4 pathway that is associated with inflammatory reactions, thereby mitigating liver fibrosis.

Topics: Actins; Alanine Transaminase; Animals; Aspartate Aminotransferases; Body Weight; Carbon Tetrachloride; Collagen; Down-Regulation; Fibrinolytic Agents; Interleukin-6; Liver; Liver Cirrhosis, Experimental; Male; Naphthoquinones; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Echinochrome A (Echi A) improves mitochondrial function in the heart; however, its effects on skeletal muscle are still unclear. We hypothesized that Echi A administration during short-term exercise may improve exercise capacity. Twenty-four male Sprague-Dawley rats were randomly divided into the following groups: control group (CG), Echi A-treated group (EG), aerobic exercise group (AG), and aerobic exercise treated with Echi A group (AEG) (n = 6 per group). Echi A was administered intra-peritoneally (0.1 mg/kg of Echi A in 300 µL phosphate-buffered saline) daily 30 min before each exercise training. The AG and AEG groups performed treadmill running (20 m/min, 60 min/day) five days/week for two weeks. The exercise capacity was significantly higher in the AG and AEG groups compared to other groups. Interestingly, the exercise capacity increased more effectively in the AEG group. The body weight in the EG tended to be slightly lower than that in the other groups. There were no significant changes in the plasma lipids among the groups. However, the gastrocnemius muscle mitochondria content was greater in the EG and AEG groups. These findings show that Echi A administration after short-term endurance training enhances exercise capacity, which was associated with an increase in skeletal muscle mitochondrial content.

Topics: Animals; Body Weight; Heart; Lipids; Male; Molecular Structure; Muscle, Skeletal; Naphthoquinones; Organ Size; Physical Conditioning, Animal; Physical Endurance; Rats; Rats, Sprague-Dawley; Sea Urchins

Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD(+)) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD(+) in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD(+) levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage.

Topics: Animals; Antineoplastic Agents; Apoptosis; Body Weight; Cisplatin; Cytokines; Inflammation Mediators; Intestine, Small; Male; Mice; Mice, Inbred C57BL; NAD; Naphthoquinones; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Sirtuin 1; Transcription Factor RelA

Plumbagin is the major active constituent in several plants including Plumbago indica Linn. (root). This compound has been shown to exhibit a wide spectrum of biological and pharmacological activities. The present study aimed to evaluate the in vitro and in vivo antimalarial activity of plumbagin including its acute and subacute toxicity in mice.. In vitro antimalarial activity of plumbagin against K1 and 3D7 Plasmodium falciparum clones were assessed using SYBR Green I based assay. In vivo antimalarial activity was investigated in Plasmodium berghei-infected mouse model (a 4-day suppressive test).. Plumbagin exhibited promising antimalarial activity with in vitro IC50 (concentration that inhibits parasite growth to 50%) against 3D7 chloroquine-sensitive P. falciparum and K1 chloroquine-resistant P. falciparum clones of 580 (270-640) and 370 (270-490) nM, respectively. Toxicity testing indicated relatively low toxicity at the dose levels up to 100 (single oral dose) and 25 (daily doses for 14 days) mg/kg body weight for acute and subacute toxicity, respectively. Chloroquine exhibited the most potent antimalarial activity in mice infected with P. berghei ANKA strain with respect to its activity on the reduction of parasitaemia on day 4 and the prolongation of survival time.. Plumbagin at the dose of 25 mg/kg body weight given for 4 days was safe and produced weak antimalarial activity. Chemical derivatization of the parent compound or preparation of modified formulation is required to improve its systemic bioavailability.

Topics: Animals; Antimalarials; Biological Availability; Body Weight; Chloroquine; Disease Models, Animal; Female; In Vitro Techniques; Malaria; Male; Mice; Mice, Inbred ICR; Naphthoquinones; Plasmodium berghei; Plasmodium falciparum; Toxicity Tests

Plumbago zeylanica L. root is widely used in Indian medicine to treat diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of plumbagin isolated from P. zeylanica L. root and its effect on GLUT4 translocation in STZ-induced diabetic rats. Plumbagin (15 and 30 mg/kg b wt) was orally administered to STZ-induced diabetic rats for 28 days. An oral glucose tolerance test was performed on 21st day. The effect of plumbagin on body weight, blood glucose, plasma insulin, total protein, urea, creatinine, liver glycogen, plasma enzymes (SGOT, SGPT and ALP) and carbohydrate metabolism enzymes (glucose-6-phosphatase, fructose-1,6-bisphosphatase and hexokinase) were investigated. GLUT4 mRNA and protein expression in skeletal muscles were also studied. Plumbagin significantly reduced the blood glucose and significantly altered all other biochemical parameters to near normal. Further, plumbagin increased the activity of hexokinase and decreased the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase significantly in treated diabetic rats. Enhanced GLUT4 mRNA and protein expression were observed in diabetic rats after treatment with plumbagin. The results indicated that plumbagin enhanced GLUT4 translocation and contributed to glucose homeostasis. It could be further probed for use as a drug to treat diabetes.

Topics: Animals; Blood Glucose; Blotting, Western; Body Weight; Creatinine; Diabetes Mellitus, Experimental; Fructose-Bisphosphatase; Gene Expression Regulation; Glucose Tolerance Test; Glucose Transporter Type 4; Glucose-6-Phosphatase; Hexokinase; Hypoglycemic Agents; Insulin; Liver Glycogen; Male; Muscle, Skeletal; Naphthoquinones; Plant Extracts; Plant Roots; Plumbaginaceae; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Toxicity Tests, Acute

NADH-quinone oxidoreductase 1 (NQO1) modulates cellular NAD(+)/NADH ratio which has been associated with the aging and anti-aging mechanisms of calorie restriction (CR). Here, we demonstrate that the facilitation of NQO1 activity by feeding β-lapachone (βL), an exogenous NQO1 co-substrate, prevented age-dependent decline of motor and cognitive function in aged mice. βL-fed mice did not alter their food-intake or locomotor activity but did increase their energy expenditure as measured by oxygen consumption and heat generation. Mitochondrial structure and numbers were disorganized and decreased in the muscles of control diet group but those defects were less severe in βL-fed aged mice. Furthermore, for a subset of genes associated with energy metabolism, mice fed the βL-diet showed similar changes in gene expression to the CR group (fed 70% of the control diet). These results support the potentiation of NQO1 activity by a βL diet and could be an option for preventing age-related decline of muscle and brain functions.

Topics: Aging; Animals; Behavior, Animal; Body Weight; Caloric Restriction; Cognition; Dietary Supplements; Energy Metabolism; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Mitochondria; Muscle, Skeletal; NAD; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones

Drugs containing a quinone moiety, such as anthracyclines, mitoxantrones and lapachol, show excellent anticancer activity. In this study, 2-butanoylamine-1,4-naphthoquinone (1) and 2-propanoylamine-1,4-naphthoquinone (2) derivatives from 2-amine-1 ,4-naphthoquinone were synthesized, and their antitumor activity in mice bearing Sarcoma 180 tumor were examined. In addition, hematology and biochemistry analyses, as well as, histopathological and morphological analyses were performed in order to evaluate the toxicological aspects of the naphthoquinones treatment. Both naphthoquinones showed potente antitumor activity. The inhibition rates were 33.48 and 42.35% for (1) and 37.65 and 55.24% for (2) at the dose of 25 and 50 mg/kg/day, respectively. In the histopathological analysis, the naphthoquinones showed only weak toxicity. Neither enzimatic activity of transaminases (aspartate aminotransferase-AST nor alanine aminotransferase-ALT), urea level nor hematological paramenter were significantly modified after naphthoquinones treatment. These data reinforce the anticancer potential of naphthoquinones derivatives.

Topics: Alanine Transaminase; Anilides; Animals; Antineoplastic Agents; Aspartate Aminotransferases; Blood Cell Count; Body Weight; Female; Kidney; Mice; Naphthoquinones; Neoplasm Transplantation; Organ Size; Sarcoma 180; Urea

DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor where IC50 for IDPc is 1.49 microM. The purpose of this study was to evaluate the effects of DA-11004 on the high fat high sucrose (HF)-induced obesity in male C57BL/6J mice. After completing a 8-week period of experimentation, the mice were sacrificed 1 hr after the last DA-11004 treatment and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat) were collected. There was a significant difference in the pattern of increasing body weight between the HF control and the DA-11004 group. In the DA-11004 (100 mg/kg) treated group the increase in body weight significantly declined and a content of epididymal fat and retroperitoneal fat was also significantly decreased as opposed to the HF control. DA-11004 (100 mg/ kg) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group. In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Dietary Fats; Dietary Sucrose; Disease Models, Animal; Drug Evaluation, Preclinical; Epididymis; Fatty Acids, Nonesterified; Hypoglycemic Agents; Isocitrate Dehydrogenase; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Naphthoquinones; Peritoneum; Time Factors; Triglycerides

Lapachol is a naphthoquinone well known for its therapeutic potential. Previous studies have shown that lapachol does not interfere with embryonic development during the pre-implantation period. However, when administered during the organogenic period at the same dose level, it induces a high fetal death incidence. To evaluate the effect of lapachol during fetogenesis, 20 pregnant Wistar rats were randomly divided into two groups: vehicle (10 mL of a 50% aqueous ethanol solution/kg body weight) and treated (100 mg of lapachol/kg body weight). Lapachol was administered from the 17th to 20th day of pregnancy. The following variables were analyzed: maternal body weight from 16th to 21st day of pregnancy, food intake from 17th to 21st day of pregnancy, clinical signs of physical discomfort, ovarian weights, implantations, resorptions and mortality indices, fetal and placenta weights, external malformations, and fetal organ weights. Results indicated that lapachol was not toxic to mothers, although it was fetotoxic leading to fetal growth retardation.

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Eating; Embryonic and Fetal Development; Female; Fetal Growth Retardation; Fetal Weight; Gestational Age; Naphthoquinones; Organ Size; Ovary; Placenta; Pregnancy; Rats; Rats, Wistar

Lapachol is a naphtoquinone with therapeutic potential against enterovirus, Chagas disease and is also used as an antimalarial and antiinflamatory agent. In order to study teratogenic potential of Lapachol, pregnant Wistar rats were treated with 0.5 ml of distilled water (control group); 0.5 ml of hydroalcoholic solution (vehicle group) and 10 mg of Lapachol in 0.5 ml of hydroalcoholic solution (treated group) by oral gavage from the 8th to the 12th day of pregnancy. The following variables were observed: maternal body weight on days 1, 6, l5 and 21 and food intake on days 2, 6, 15 and 21 of pregnancy. The number of live and dead fetuses and the sites of resorptions were counted. The ovaries were weighed and the corpora lutea were counted. Data were analyzed by ANOVA-one way, Dunnett test and the chi square test. Significance level test alpha = 0.05. Results have shown that mothers were unaffected but there were a 99.2% of fetus mortality, indicative of a strong abortifacient effect of Lapachol in rats.

Topics: Animals; Anti-Infective Agents; Body Weight; Chi-Square Distribution; Corpus Luteum; Female; Fetal Death; Naphthoquinones; Organ Size; Pregnancy; Rats; Rats, Wistar; Toxicity Tests

The use of drug delivery systems may reduce the toxicity and improve the activity of anti-leishmanial compounds. The activity of atovaquone (ATV)-loaded liposomes was compared by determination of median effective doses (ED(25) and ED(50)), with that of free ATV in a murine model of visceral leishmaniasis induced by Leishmania infantum. On day 0, mice were infected intravenously with 4.10(7) promastigotes and treated via the tail vein on days 15, 17 and 19 by free drug in a DMSO/cremophor/water solution (0.2 to 1.6 mg/kg body weight) or by liposomal drug (0.04 to 0.32 mg/kg body weight). Mice were killed and livers and spleens were removed and weighed on day 21 p.i. and liver parasite burdens evaluated using the Stauber method. Effective doses were determined using the Hill representation relating the percentage of parasite suppression to the dose. Liposomal ATV was significantly more effective than the free drug in reducing liver parasites (61.6% of parasite suppression at a dose of 0.32 mg/kg vs 34.9% at a dose of 1.6mg/kg). Liposomal ATV was 23 times more active than the free drug (ED(25) value=0. 02+/-0.01 mg/kg vs 0.46+/-0.15 mg/kg for free drug). It was not possible to obtain the ED(50) for free ATV because the dose-response curve reached a plateau around 33% of parasite suppression. Conversely, the ED(50) for liposomal ATV was 0.17+/-0.05 mg/kg. 100% efficacy of bound ATV could be obtained with a concentration of 1. 77+/-0.35 mg/kg. A significant decrease in spleen weights was also observed reflecting a leishmanicidal activity of ATV. These results suggest that liposome loaded ATV is more efficacious than the free drug against Leishmania infantum in this murine model.

Topics: Animals; Antiprotozoal Agents; Atovaquone; Body Weight; Drug Compounding; Leishmania infantum; Leishmaniasis, Visceral; Liposomes; Liver; Male; Mice; Mice, Inbred BALB C; Naphthoquinones; Spleen

Two new compounds, pycnanthuquinone A (1) and pycnanthuquinone B (2), were isolated from leaves and stems of the African plant, Pycnanthus angolensis (Welw.) Warb (Myristicaceae), by bioassay-guided fractionation of an ethanolic extract using a diabetic mouse model. Pycnanthuquinones A and B are the first representatives of a novel terpenoid-type quinone skeleton, and both compounds possess significant antihyperglycemic activity.

Topics: Africa; Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Eating; Fatty Acids, Unsaturated; Hypoglycemic Agents; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Naphthoquinones; Plant Extracts; Plant Leaves; Plant Stems; Plants, Medicinal

Lapachol is a naphtoquinone with therapeutic potential against Chagas disease and is also used as an antimalarial agent. To study the reproductive toxicity potential of Lapachol, pregnant Wistar rats were treated with 0.5 mL of distilled water (control group), 0.5 mL of hydroalcoholic solution (vehicle group), or 20 mg of Lapachol in 0.5 mL of hydroalcoholic solution (treated group) by oral gavage from the 8th to the 12th day of pregnancy. The following variables were observed: maternal body weight on days 1, 6, 15, and 21; food intake on days 2, 6, 15, and 21 of pregnancy. The number of live and dead fetuses and the sites of resorptions were counted. The ovaries were weighed and the corpora lutea were counted. Data were analyzed by ANOVA one-way Dunnett test and chi 2 test. Results showed that mothers were uneffected but there was 100% fetal/embryo mortality, indicative of a strong interceptive effect of Lapachol in rats.

Topics: Animals; Antimalarials; Body Weight; Eating; Embryo Implantation; Female; Fetal Death; Fetal Resorption; Naphthoquinones; Pregnancy; Rats; Rats, Wistar; Time Factors; Trypanocidal Agents

The weight changes, carrier state and nature of chronic disease in cattle following infection with five isolates of Theileria parva and treatment with parvaquone were studied over an 18 month period while the cattle were maintained on normal management under strict tick control. Cattle infected with the T.p. parva Pugu II isolate gained weight similarly to uninfected control cattle and did not develop a detectable carrier state or show chronic disease. The cattle in the 4 other isolate groups regained the weight lost during the initial infection more slowly, then gained weight in parallel to the control cattle. Transmission of infection through ticks was achieved consistently from the T.p. parva Mbita I and Entebbe II isolate infections and intermittently from the T.p. lawrencei Mara II and Manyara infections. Infections were transmitted from cattle which had neither a detectable parasitaemia nor an antitheilerial antibody titre. Persistent macroschizont parasitoses were detected with the T.p. parva Entebbe II and the two T.p. lawrencei infections. The histopathology of the chronic disease lesions is described and the importance of the carrier state discussed.

Topics: Animals; Apicomplexa; Arachnid Vectors; Body Weight; Carrier State; Cattle; Male; Naphthoquinones; Theileriasis; Ticks

Dietary exposure of rats to a high concentration of 2,3-dichloro-1,4-naphthoquinone (CNQ) (2 g/kg diet) for 60 days altered cardiac mitochondrial function and activities of anti-oxidant enzymes in hepatic and cardiac tissue. CNQ moderately depressed the cardiac mitochondrial respiratory control ratio (RCR) to 85% of control; this was exacerbated to 60% of control in animals fed alpha-tocopherol-deficient diets. Dietary CNQ increased hepatic superoxide dismutase (SOD) and catalase activities and increased cardiac SOD activity, but depressed cardiac glutathione reductase and hepatic glutathione peroxidase activities. These effects are consistent with previous in vitro findings that CNQ induces oxidative stress. No significant differences in heart weight or body weight were observed in rats fed CNQ as compared to untreated controls.

Topics: Animals; Antioxidants; Body Weight; Catalase; Diet; Glutathione Peroxidase; Glutathione Reductase; Heart; Liver; Myocardium; Naphthoquinones; Organ Size; Oxygen Consumption; Rats; Superoxide Dismutase; Vitamin E Deficiency

Topics: Animals; Body Weight; Carcinogens; Carcinoma, Hepatocellular; Chemical and Drug Induced Liver Injury; Chlorine; Diet; Dose-Response Relationship, Drug; Female; Lethal Dose 50; Liver; Liver Cirrhosis; Liver Neoplasms; Lung Neoplasms; Male; Mice; Mice, Inbred Strains; Mycotoxins; Naphthoquinones; Necrosis; Oryza; Penicillium; Peptides, Cyclic; Sex Factors

Topics: Animals; Body Weight; Carbon Dioxide; Chemical Phenomena; Chemistry; Epinephrine; Hypoxia; Malaria; Methods; Mice; Morphine; Naphthoquinones; Organ Size; Oxygen Consumption; Plasmodium; Pulmonary Edema; Time Factors

Topics: Acids; Adenocarcinoma; Alkaloids; Animals; Antineoplastic Agents; Benzopyrans; Body Weight; Depression, Chemical; Mammary Neoplasms, Experimental; Mice; Naphthoquinones; Neoplasm Transplantation; Nuts; Plant Extracts