Evaluating the Effect of PIH on Rats-Liver Overloaded with Iron
Journal Title: IOSR Journal of Pharmacy and Biological Sciences (IOSR-JPBS) - Year 2016, Vol 11, Issue 6
Abstract
The accumulation of iron (Fe) in the liver is a serious complication of thalassemia and other ironloading anemias requiring long-term blood transfusions. Such patients are directed to suffer death unless they are treated with Fe chelating agents. Desferrioxamine (DFO), deferiprone (L1) and desferasirox (ICL-670) are clinically approved iron chelators used to treat secondary iron overload, but there is still need for new drug candidates due to limited long-term efficacy and drug toxicity. Pyridoxalisonicotinoylhydrazone (PIH) is tridentating iron chelator effective at scavenging and mobilizing iron. Therefore, the present study was undertaken to evaluate the role of PIH to improve rat antioxidant systems against iron overload (IOL) induced hepatic oxidative stress. To produce IOL, rats were intraperitoneal(IP) injected by 50 mg iron–sorbitol–citric acid complex/100g b.w. subcutaneously on four successive days.AST and ALT activities, moreover, MDA, TBARS and NO levels were significantly (p<0.05) increased. The toxic effect of iron was also indicated by significant (p<0.05) decrease in the levels of liver GSH, Gpx, CAT, SOD and Ceruloplasmin when compared with the control rats. Administration of PIH at different doses 50 mg PIH/kgb.w.(low dose) and 100 mg PIH/Kg b.w. (high dose), significantly (p<0.05) reversed the levels of AST, ALT, MDA, TBARS and NO levels and restored the levels of GSH, Gpx, CAT, SOD and Ceruloplasmin to the normal levels. This study provides in vivo evidence that PIH administration can improve the antioxidant defense systems against IOL-induced hepatic oxidative stress in rats. This therapeutic effect of PIH in iron overloaded rats liver may be due to both the antioxidant and metal chelation activities.
Authors and Affiliations
Marwan A . Ibrahim1, Alaa-Eldin Salah-Eldin2
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