Thermoregulatory and In-vivo Anti-inflammatory Effects of Vigabatrin In Rat and Mice

Effects of acute administration of vigabatrin (VGB) that has significant GABA-mimetic properties were studied for its antiinflammatory, antigranuloma effects in rats and thermoregulatory actions in mice. Treatment of rats with VGB (125, 250 and 500 mg/kg, i.p doses) caused a significant and persistent inhibition in the carrageenan induced paw edema. Inhibitory effect at high dose (500 mg/kg, which was about 10-fold of the maximal effective dose 50 mg/kg in humans) was 40-, 41- and 39% of the control at 2-, 3- and 4 hours afier the treatment. In cotton-pellet-granuloma study, only the high dose was significantly (P<0.05) effective and inhibition in granuloma was 17 and 28% of the control at 250 and 500 mg/kg doses, respectively. In another model, leukocyte migration to the inflamed peritoneal cavity was used as a parameter in rats. In this model, VGB (500 mg/kg, i.p) induced a significant (P<0.05) reduction in leukocyte migration to the inflamed peritoneal cavity when administered 30 min before carrageenan. This was comparable to indomethacin (10 mg/kg) that also caused a significant (P<0.05) reduction in leukocyte migration. The inhibition in the leukocyte migration was 66 and 61% with VGB and indomethacin, respectively. In thermoregulation studies, the rectal temperature of normothermic mice declined dose dependently. In another part of this study all the doses of VGB induced a significant reduction in body temperature at 45 min following drug administration in yeast-induced hyperpyrexic mice. The hypothermic response diminished after 90 min, 3 hours and 6 hours of treatment at 125, 250 and 500 mg/kg doses respectively and none of the dose showed any change in rectal temperature at 24-hour study point. The results of the present study indicate that vigabatrin has the potential to induce anti-edema, antigranuloma and leukocyte anti-migratory effects in inflamed peritoneal cavity and reduce the rectal temperature in normothermic as well as hyperthermia-induced mice with acute regimen. These effects are thought to be the result of GABA accumulation, its interaction with PG biosynthesis and other neuromediators

The Beneficial Interaction Between Enalapril and Danazol in Normal Rat

Danazol, a weekly androgenic, heterocyclic compound with anabolic properties, is used primarily in the treatment of endometriosis and other gynecological complaints. Effects of co-administration of enalapril, an angiotensin converting enzyme inhibitor (ACE inhibitor) with danazol on some biochemical parameters in rats were studied. Treatment of rats with danazol (200mglkg i.p) for 15 days induced a significant elevation of serum aspartate transaminase activity (AST, EC: 2.6.1.1), triglycerides (TG) and induced a significant decrease in serum cholesterol. However, enalapril treatment (20mglkg i.p) for 15 days caused a significant elevation of serum alanine transaminase activity (ALT, EC: 2.6.1.2). Co-administration of danazol and enalapril significantly lowered the elevated levels of serum transaminases enzyme activities and serum TG. It could be concluded that long term treatment with enalapril might be beneficial in patients danazol in clinical situations through protection against undesirable side effects