Enhancement of Liver Toxicity on Diabetes Mellitus by a Universal Chemical Pollutant (Acrylonitrile) in Rats

Sameer E. Alharthi
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Abstract

The present study was designed to investigate potential liver damage due to acrylonitrile in Streptozotocin induced diabetes in rats. Twenty-four rats were divided into 4 treatment groups. Nondiabetic control rat receiving distilled water, non-diabetic rat receiving acrylonitrile aqueous solution (10 mg/kg/day), diabetic control rat receiving distilled water and diabetic rat receiving acrylonitrile aqueous solution. All groups received the treatment for 4 weeks. The animals were assessed for hepatoxicity markers in serum, oxidative stress markers, CYP2E1 activity and cyanide formation in tissues. Acrylonitrile significantly elevated serum aminotransferase, alanine aminotransferase, total bilirubin levels, triglycerides and total cholesterol in diabetic groups as compared to normal control group. Antioxidant markers like glutathione showed significant decline while a significant increase in malondialdehyde, superoxide dismutase and catalase in diabetic rats treated with acrylonitrile. CYP2E1 activity was observed in acrylonitrile – exposed nondiabetic and diabetic groups as compared to control. Cyanide formation was raised in both the nondiabetic and diabetic groups as compared to control group. Acrylonitriles can produce acute hepatic injury, induction of diabetes mellitus type II, and accomplish the CYP2E1 enzyme which sequentially leads to generation of oxidative stress and its metabolic product–cyanide that may potentiate the oxidative stress posing more deleterious effect.
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通用化学污染物丙烯腈对糖尿病大鼠肝毒性的增强作用
本研究旨在探讨丙烯腈对链脲佐菌素诱导的糖尿病大鼠的潜在肝损害。24只大鼠分为4个治疗组。非糖尿病对照组大鼠接受蒸馏水,非糖尿病大鼠接受丙烯腈水溶液(10 mg/kg/天),糖尿病对照组大鼠接受蒸馏水,糖尿病大鼠接受丙烯腈水溶液。各组均治疗4周。测定小鼠血清中肝毒性标志物、氧化应激标志物、组织中CYP2E1活性和氰化物形成。与正常对照组相比,丙烯腈显著提高糖尿病组血清转氨酶、丙氨酸转氨酶、总胆红素水平、甘油三酯和总胆固醇。抗氧化指标如谷胱甘肽显著下降,丙二醛、超氧化物歧化酶和过氧化氢酶显著升高。与对照组相比,观察了暴露于丙烯腈的非糖尿病组和糖尿病组的CYP2E1活性。与对照组相比,非糖尿病组和糖尿病组的氰化物形成都有所增加。丙烯腈可引起急性肝损伤,诱导II型糖尿病,并完成CYP2E1酶的作用,从而导致氧化应激的产生,其代谢产物氰化物可加重氧化应激,造成更大的危害。
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