Study of the effect of thyroid gland dysfunction on the blood levels of caspase-3, some mediators of innate inflammation, matrix metalloproteinase-9 and some liver functions in rats

In the present study we have measured the concentrations of serum IL-6, TNF-alpha, MMP-9 and hepatic caspase-3 activity in rats with hypothyroidism and hyperthyroidism together with total T[3], AST and ALT. We have evaluated the effect of thyroid dysfunction in an experimental model. We studied 45 rats. Fifteen served as controls, 15 rats were hypothyroid and 15 were hyperthyroid. Serum ALT and AST were found to be significantly higher in the hyperthyroid group. Serum IL-6 and TNF-alpha concentrations were significantly higher in the hyperthyroid group compared to the hypothyroid group. The mean values of hepatic caspase-3 were significantly elevated in the hyperthyroid group as compared to the control group. Less caspase-3 activity was found in the hypothyroid group compared to the control group. The mean values of MMP-9 were found to be significantly increased in the hyperthyroid group as compared to both the hypothyroid and the control groups. Our study shows that excess T3 causes liven dysfunction through the following mechanism [s]: 1] inducing apoptosis, as a result of activation of a mitochondnia-dependent pathway; 2] direct toxic effect, as evidenced by increased levels of proinflammatory cytokines IL-6 and TNF-alpha; 3] elevated MMP-9 levels may also reflect a possible role for Kupffen cells in the hepatocellular response to hepatic injury by secretion of MMP-9

study of some mediators of innate inflammation in an experimental model of colitis in rats

Although leptin, an adipocyte derived hormone which regulates food intake and energy balance, is released after injections of tumour necrosis factor [TNF] and interleukin-1, plasma concentrations have not been characterized in cases of inflammation. Leptin may contribute to the anorexia and body weight loss associated particularly with the acute stages of inflammatory bowel disease [IBD]. The aims of the present study was to investigate serum TNF-alpha levels and plasma leptin concentrations in an experimental model of iodoacetamide-induced colitis and to evaluate the effects of L-glutamine in that model of experimental colitis in rats. Plasma leptin was measured on the tenth day in rats with iodoacetamide-induced colitis. Systemic TNF-alpha was also measured. Colitis was induced by intracolonic administration of 3% iodoacetamide. In the treatment group, L-glutamine 400 mg/kg was given daily by gavage and continued for 7 days until the rats were sacrificed. Their colons were then processed for wet weight, lesion area, weight of mucosal scraping and myeloperoxidase activity. Colonic wet weight, lesion area, myeioperoxidase activity and serum levels of TNF-alpha were significantly lower [P <0.05] in the treatment group [iodoacetamide + L-glutamine] than the control group [iodoacetamide only]. Moreover, plasma leptin concentrations increased significantly in group I [colitis] when compared to group II [colitis + L-giutamine]. Anorexia and body weight loss were observed in group I when compared to group II [treatment group]. L-glutamine effectively decreases colitis induced by iodoacetamide. This mechanism is probably associated with inhibition of TN F-alpha and should be further studied

Effect of experimental acute Ischemic renal injury on hepatoprotective parameters in rats

This study evaluated the effects of DHEA on the oxidant [malondialdehyde [MDA]] and antioxidant [superoxide dismutase [SOD], glutathione penoxidase [GPx], catalase [CAT], and glutathione [GSH] systems in liver after renal-ischemia reper fusion [IR] injury in rats. Thirty rats were randomly assigned to 3 groups of 10: group I [Sham operation], group II [renal IR group], and group III [DHEA, 25 mg/kg, sc, 15 min pre-ischemia]. Renal IR injury in group II caused a decrease of SOD [25%], GPx [36%] and CAT [26%] activities and GSH levels [32%] and increases of MDA [30%] in liver and of ALT and AST activities in serum, compared to group I. DHEA administration decreased the hepatic MDA level [19%] and serum ALT activity [30%] [P < 0.01 and P < 0.05, respectively], and considerably increased hepatic GSH levels and GPx activities [P < 0.01 for both] in group III, compared to group II. These results suggest that DHEA treatment has beneficial effects on antioxidant defenses against hepatic injury after renal IR in rats, possibly by augmenting GSH levels and lowering MDA production