Association between Paraoxonases Gene Expression and Oxidative Stress in Hepatotoxicity Induced by CCl 4

Objectives. The purpose of the study is to evaluate the hepatoprotective effect of rutin in carbon tetrachloride- (CCl4-) induced liver injuries in rat model. Methods. Forty male Wistar albino rats were divided into four groups. Group I was the control group and received dimethyl sulphoxide (DMSO) and olive oil. Group II received rutin. Groups III was treated with CCl4. Group IV was administered rutin after 48 h of CCl4 treatment. Liver enzymes level, lipid profile, lipid peroxidation, and hydrogen peroxide were measured. The genes expression levels were monitored by real time RT-PCR and western blot techniques. Results. CCl4 group showed significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBAR), hydrogen peroxide (H2O2), and lipid profile and a significant decrease in glutathione peroxidase (GPx), glutathione S transferase (GST), catalase (CAT), paraoxonase-1 (PON-1), paraoxonase-3 (PON-3), peroxisome proliferator activated receptor delta (PPAR-δ), and ATP-binding cassette transporter 1 (ABAC1) genes expression levels. Interestingly, rutin supplementation completely reversed the biochemical and gene expression levels induced by CCl4 to control values. Conclusion. CCl4 administration causes aberration of genes expression levels in oxidative stress pathway resulting in DNA damage and hepatotoxicity. Rutin causes hepatoprotective effect through enhancing the antioxidant genes

Downregulation of Oxidative and Nitrosative Apoptotic Signaling by L-Carnitine in Ifosfamide-Induced Fanconi Syndrome Rat Model

It is well documented that ifosfamide (IFO) therapy is associated with sever nephropathy in the form of Fanconi syndrome. Although oxidative stress has been reported as a major player in IFO-induced Fanconi syndrome, no mechanism for this effect has been ascertained. Therefore, this study has been initiated to investigate, on gene expression level, the mechanism of IFO-induce nephrotoxicity and those whereby carnitine supplementation attenuates this serious side effect of IFO. To achieve the ultimate goals of this study, adult male rats were assigned to one of four treatment groups, namely, control, L-carnitine, IFO, and IFO plus L-carnitine. Administration of IFO for 5 days significantly increased serum creatinine, blood urea nitrogen (BUN), and total nitrate/nitrite (NOx) production in kidney tissues. In addition, IFO significantly increased mRNA expression of inducible nitric oxide synthase (iNOS), caspase-9, and caspase-3 and significantly decreased expression of glutathione peroxides (GPx), catalase (CAT), and Bcl2 in kidney tissues. Administration of L-carnitine to IFO-treated rats resulted in a complete reversal of the all biochemical and gene expression changes, induced by IFO, to the control values. Data from this study suggest that L-carnitine prevents the development of IFO-induced nephrotoxicity via downregulation of oxidative and nitrosative apoptotic signaling in kidney tissues

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

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