dinoprost and Edema

This study investigated the cardioprotective effect of N-acetylcysteine (NAC) on isoproterenol (ISO)-induced cardiotoxicity in rats. Male Sprague-Dawley rats were divided into control, NAC alone (100 mg/kg BW orally for 14 days), ISO-control (85 mg/kg BW), and ISO with NAC (for 14 days). Serum creatine kinase-MB and Lactate dehydrogenase were measured. From the heart homogenate lipid hydroperoxides (LPO), superoxide dismutase (SOD), total glutathione (GSH), and 8-isoprostane (IP) were measured. Histopathological examination of the heart was also carried out. There was a significant increase (P < 0.05) in LPO and IP levels in ISO-control group and NAC treatment reduced these changes. Antioxidant enzyme, SOD and GSH, level decreased significantly (P < 0.05) in ISO-control group, and treatment with NAC was able to reverse these changes significantly (P < 0.05). Histopathologically, ISO-control group showed morphological changes suggestive of cardiotoxicity with large areas of coagulative necrosis, with diffused interstitial edema. NAC treatment successfully reduced these histopathological changes. In conclusion, the study proves that NAC has a strong cardioprotective effect against isoproterenol-induced cardiac changes. NAC decreases isoproterenol-induced LPO and IP levels in the heart tissue and prevented free radicals-induced damage to the myocardium.

Topics: Acetylcysteine; Animals; Body Weight; Cardiotonic Agents; Creatine Kinase, MB Form; Dinoprost; Drug Therapy, Combination; Edema; Free Radical Scavengers; Glutathione; Heart; Isoproterenol; L-Lactate Dehydrogenase; Lipid Peroxidation; Male; Myocardium; Necrosis; Organ Size; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

The contribution of nitric oxide (NO) to articular pain in arthritis induced by zymosan (1 mg, intra articular) in rats was assessed by measuring articular incapacitation (AI). Systemic treatment with the non-selective NO synthase (NOS) inhibitor L-NAME (10 - 100 mg kg(-1) i.p.) or with the selective iNOS inhibitors aminoguanidine (AG; 10 - 100 mg kg(-1) i.p.) or 1400W (0.5 - 1 mg kg(-1) s.c.) inhibited the AI induced by injection of zymosan 30 min later. Local (intra articular) treatment with the NOS inhibitors (L-NAME or AG, 0.1 - 1 micromol; 1400W, 0.01 (micromol) 30 min before zymosan also inhibited the AI. Systemic or local treatment with the NOS inhibitors (L-NAME; AG, 100 mg kg(-1) i.p. or 0.1 micromol joint(-1); 1400W, 1 mg kg(-1) s.c. or 0.01 micromol joint(-1)), 2 h after zymosan did not affect the subsequent AI. Local treatment with the NO donors SNP or SIN-1, 2 h after zymosan did inhibit AI. L-NAME and AG, given i.p. inhibited nitrite but not prostaglandin E(2) (PGE(2)) levels in the joints. L-NAME (100 mg kg(-1)) but not AG (100 mg kg(-1)) increased mean arterial blood pressure. Neither L-NAME, AG nor the NO donor SIN-1 altered articular oedema induced by zymosan. In conclusion, inhibitors of iNOS decrease pain in zymosan arthritis only when given before the zymosan. This was not due to inhibition of articular PGE(2) release or oedema. NO donors also promoted antinociception in zymosan arthritis without affecting oedema.

Topics: Amidines; Animals; Arthritis, Experimental; Benzylamines; Cartilage, Articular; Dinoprost; Edema; Enzyme Inhibitors; Guanidines; Injections, Intra-Articular; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Pain; Pain Measurement; Rats; Rats, Wistar; Zymosan

Xeroderma pigmentosum group A (XPA) gene-deficient mice cannot repair UV-induced DNA damage and easily develop skin cancers by UV irradiation. Therefore, XPA-deficient mice are a useful model of human XP and represent a promising tool for photobiologic studies of the disorder. Exposure to ultraviolet (UV) B (280-320 nm) radiation greatly enhanced inflammation and immunosuppression in these mice. To investigate the molecular mechanisms of enhanced UV inflammation and immunosuppression, we determined the amount of prostaglandin (PG) E2, an inflammatory mediator and immunomodulator, and analysed the expression of cyclooxygenase (COX) mRNA in the ear skin of XPA-deficient mice after UV irradiation. In XPA-deficient mice, the amount of PGE2 significantly increased at 48 and 72 h after UVB irradiation to the level that was 8- and 16-fold higher than those in wild-type mice, respectively. The expression level of COX-2 mRNA increased in a time-dependent manner, although COX-1 mRNA was constantly expressed. Treatment with indomethacin, a potent inhibitor of PG biosynthesis, inhibited UV-induced ear swelling, abrogated local immunosuppression, and decreased the amount of PGE2 in the ear skin of XPA-deficient mice. These results indicate that the excess DNA photoproducts remaining in XPA-deficient cells after UV radiation may induce COX-2 expression. The induced production of PGE2 may be involved in the enhanced inflammation and immunosuppression caused by UV radiation in XPA-deficient mice and XP patients.

Topics: Animals; Cyclooxygenase 1; Cyclooxygenase 2; Cytosol; Dinoprost; Dinoprostone; Disease Models, Animal; Ear; Edema; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Immune Tolerance; Indomethacin; Isoenzymes; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Phospholipases A; Photosensitivity Disorders; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; RNA, Messenger; Ultraviolet Rays; Xeroderma Pigmentosum

This study examined the pro- and anti-inflammatory effects of the stable prostaglandin (PG) D2 analogue, ZK 118.182 and the mechanism by which prostaglandins may exert their anti-inflammatory activity. Co-injected locally, ZK 118.182, like PGE2 and PGD2, dose-dependently increased plasma leakage induced by intradermal injection of bradykinin in rabbit skin. Infused i.v., ZK 118.182 (0.45 microgram/kg/min), a dose which did not affect systemic blood pressure, inhibited oedema formation in rabbit skin induced by the neutrophil-dependent agonists, formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4). However, it did not modify plasma leakage induced by the neutrophil-independent mediators, bradykinin and platelet-activating factor (PAF). In contrast, neutrophil accumulation in response to LTB4 and FMLP was not affected in animals infused with ZK 118.182. In vitro, ZK 118.182, like PGE2 and PGD2 inhibited FMLP-induced superoxide anion (O2-) production by rabbit neutrophils. The compound, however, had minimal effects on O2- production induced by phorbol myristate acetate (PMA). ZK 118.182 inhibited to a small extent FMLP but not PMA-induced neutrophil adherence. These results show that depending on the route of administration, the PGD2 analogue, ZK 118.182, exhibits either pro- or anti-inflammatory effects. The anti-inflammatory effect may be related to the ability of the compound to inhibit increased microvascular permeability induced by neutrophil activation without interfering with neutrophil accumulation. This latter effect may be due to the analogue's capacity to suppress neutrophil secretion to a greater extent than neutrophil adherence.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Dinoprost; Edema; In Vitro Techniques; Indium Radioisotopes; Inflammation Mediators; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Platelet Aggregation Inhibitors; Prostaglandin D2; Rabbits; Skin; Superoxides

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate Lipoxygenases; Arthritis, Experimental; Carrageenan; Cyclooxygenase Inhibitors; Dinoprost; Edema; Inflammation; Leukemia, Basophilic, Acute; Leukotriene B4; Lipoxygenase Inhibitors; Mycobacterium; Phenols; Pyrazoles; Rats; Stomach Ulcer; Tumor Cells, Cultured; Zymosan

Local variations of prostaglandin (PG) I2 and F2 alpha were studied in the pancreatic tissue during the first hour of an acute experimental necrohemorrhagic pancreatitis. The local pancreatitis was induced by trypsin injection into the interstitium of the splenic part of rat pancreas, and a saline injection was given into the interstitium in the duodenal part of the same pancreas as control. PGF2 alpha level was measured by specific radioimmunoassay (RIA), and the stable degradation product of PGI2, the 6-keto-PGF1 alpha, was determined also by RIA as an index of PGI2 level. The results were compared between the two regions and with control intact pancreata. The PGI2 level transiently decreased, whereas the PGF2 alpha increased in the region of localized hemorrhagic pancreatitis when compared with the intact pancreata. By contrast, the quickly disappearing edematous reaction induced by saline injection was accompanied by opposite changes in the two PGs studied: PGI2 was transiently elevated and PGF2 alpha diminished. In consequence, the ratio of the two PGs was shifted in favor of PGI2 in a transient edematous reaction and in favor of PGF2 alpha in hemorrhagic pancreatitis. It was concluded that PGI2 plays some protective role while PGF2 alpha might be one of the aggressive mediators in the inflammatory process. Their biological importance must be limited since PGF2 alpha alone did not induce pancreatitis nor did PGI2 protect against the trypsin-induced local pancreatitis.

Topics: Acute Disease; Animals; Dinoprost; Edema; Epoprostenol; Female; Kinetics; Pancreas; Pancreatitis; Prostaglandins E; Prostaglandins F; Rats; Reference Values; Trypsin

The possible modulatory effect of central prostaglandins (PGs) on carrageenan-induced pedal inflammation, was investigated in rats. Intracerebroventricularly (i.c.v.) administered arachidonic acid, the PG precursor, produced a statistically insignificant increase in the inflammatory response, though PG synthesis inhibitors, administered by the same route, markedly attenuated the oedema. Centrally administered PGE2 had a significant pro-inflammatory effect, whereas PGF2 alpha exerted an anti-inflammatory action. The results indicate that central PGs may modulate peripheral inflammation and that, at least partly, the anti-inflammatory activity of PG synthesis-inhibiting non-steroidal anti-inflammatory agents may involve central PGs, as has been proposed for their analgesic effect.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Aspirin; Carrageenan; Diclofenac; Dinoprost; Dinoprostone; Edema; Female; Injections, Intraventricular; Male; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats

Bradykinin (BK) produced a dose-related increase in the paw volume of the rat. Responses to BK at all doses used were not affected by pretreating the rats with diphenhydramine, 1 mg kg-1, or indomethacin, 2.5 and 5 mg kg-1. Indomethacin, 10 mg kg-1 produced a small but significant reduction in the responses to BK. Captopril 1 mg kg-1 enhanced responses to low but not to high doses of BK. The rank order of potency of various kinin analogues to increase paw volume was found to be methionyl-lysyl-BK (met-lys-BK) greater than BK greater than lysyl-BK (Kallidin) much greater than des-Arg9-BK. The B1-receptor antagonist des-Arg9-Leu8-BK did not affect responses to BK on paw volume. Two modified kinin fragments S2302 (H-D-Pro-Phe-Arg-p-Nitroaniline) and S2441 (H-D-Pro-Phe-Arg-NH-heptyl) produced dose-related increases in paw volume both having approximately half the potency of BK. These responses were not antagonised by diphenhydramine, 1 mg kg-1 which reduced significantly the response to histamine. On the isolated rat uterus the rank order of potency of various kinins was BK greater than Kallidin greater than met-lys-BK greater than des-Arg9-BK. The two modified kinin fragments S2302 and S2441 (but not des-Arg9-Leu8-BK) antagonised BK induced contractions of the rat uterus. From the rank order of potency studies the receptor mediating contraction of the rat uterus in vitro and increase in rat paw volume to BK appear to be of the same type.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bradykinin; Dinoprost; Edema; Female; Foot; In Vitro Techniques; Kallidin; Kinins; Male; Oxytocin; Prostaglandins F; Rats; Rats, Inbred Strains; Uterine Contraction; Uterus

Carrageenin-induced pedal inflammation in rats, was found to significantly enhance brain levels of prostaglandin (PG) E2 and PGF2 alpha. PG levels increased after 30 min of induction of the inflammation, peaked at 1 h, and attained normal levels by 4 h. Bilateral adrenalectomy had little effect on carrageenin-induced increase in rat brain PGs. The pattern of elevation of central PGs and the time course of carrageenin inflammation were at variance, the latter peaking between 3 and 4 h. The findings lend credence to the postulate that inflammatory hyperalgesia involves participation of central pain circuits, and that fever accompanying inflammation is caused by the central release of PGs. The central nociceptive and hyperthermic actions of PGs are well documented. However, the increase in central PG levels may well be caused by stress induced by the peripheral inflammation, since the pattern of elevation in either case is qualitatively similar.

Topics: Adrenalectomy; Animals; Brain; Carrageenan; Dinoprost; Dinoprostone; Edema; Female; Foot Diseases; Male; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Time Factors

An analytical method for measuring in vivo inhibition of prostaglandin (PG) synthesis by nonsteroidal anti-inflammatory drugs was developed for estimation of urinary prostaglandin levels in rats. Drugs were administered orally to rats (Wistar, male, 200-250 g), and water (2.5 ml/100 g body weight) was given 1 hr after drug administration to yield a constant volume of urine. Urine was collected for 4 hr after drug administration, and urinary PGE2 and PGF2 alpha were determined by radioimmunoassay. The urine volume in the 4-hr period was 5.0 +/- 0.30 ml per rat, and prostaglandin contents in the 4-hr urine were 4.56 +/- 0.56 ng PGE2 and 1.31 +/- 0.24 ng PGF2 alpha per rat in the no-drug control group. Administration of nonsteroidal anti-inflammatory drugs decreased the urinary PGE2 and PGF2 alpha dose dependently. The activities of ten typical nonsteroidal anti-inflammatory drugs in reducing urinary PGE2 excretion were compared with their anti-inflammatory activities in rats. A close correlation (r = 0.98, P less than 0.001) between the dose required for 50% reduction of urinary PGE2 excretion and the dose required for 50% inhibition of carrageenin edema was found for each drug. These drugs were also tested for their inhibitory effects on PGE2 biosynthesis in a cultured system of mouse 3T6 fibroblast cells and on prostaglandin synthesizing system in bovine seminal vesicle microsomes. No close correlation was observed between anti-inflammatory activities and inhibition of prostaglandin biosynthesis in vitro.

Topics: Animals; Anti-Inflammatory Agents; Cattle; Dinoprost; Dinoprostone; Edema; Fibroblasts; Male; Mice; Microsomes; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Seminal Vesicles

Systemic treatment of rats with captopril (50 mg/kg body wt per os), a specific competitive inhibitor of angiotensin l-converting enzyme, significantly inhibits vascular permeability changes induced by the intradermal injection of the vasoactive mediators histamine, bradykinin, serotonin, and compound 48/80. This effect of captopril is both dose- and time-dependent with approximately 60% inhibition of edema formation observed 7 h after captopril treatment (100 mg/kg body wt per os). The inhibitory effect of captopril on edema formation is temporally unrelated to the inhibition of serum angiotensin l-converting enzyme activity or serum prostaglandin E2 levels and is not inhibited by systemic treatment of rats with indomethacin. The data suggest that captopril may have potent antiinflammatory activity through as yet undefined mechanisms.

Topics: Animals; Bradykinin; Capillary Permeability; Captopril; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Edema; Male; Peptidyl-Dipeptidase A; Proline; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Skin; Thromboxane B2

In the isolated perfused hind legs of rats with enemas induced by carrageenin, dextran or Freund's adjuvant in both paws, resting perfusion pressure was slightly increased whereas the vasopressor action of noradrenaline, lysine-vasopressin and prostaglandin F2 alpha, was decreased. Admixture of indomethacin (3 micrograms.ml-1) to the perfusion fluid led to a decrease of resting perfusion pressure whereas its influence on EAmax of noradrenaline was only weak under these conditions. Concomitantly, the contents of prostaglandin E-like substances in the perfusate decreased. Prostaglandin F2 alpha exhibits only weak vasopressor activity in isolated perfused hind legs of rats with carrageenin edema. Altogether, the effect of indomethacin on resting perfusion pressure as well as on EA and EAmax, resp., of agonists is difficulty to explain by its effect on arachidonic acid cascade. The pD2-value of noradrenaline (4.68 - 4.87) and lysine-vasopressin (6.02 - 6.04) was apparently not changed, at least not decreased, in the acute phase of inflammation indicating no impairment of receptor affinity of noradrenaline and vasopressin in inflammation. Blood vessel reaction is apparently influenced in inflammation mechanically by the increased tissue pressure as well as by molecular mechanisms consisting in the presence of inflammatory mediators and/or particularly in a reduced intrinsic sensitivity of the blood vessel muscle itself.

Topics: Animals; Arthritis; Arthritis, Experimental; Blood Vessels; Dinoprost; Edema; Female; Hindlimb; In Vitro Techniques; Indomethacin; Norepinephrine; Perfusion; Prostaglandins F; Rats; Rats, Inbred Strains; Vasopressins