Treatment with omega-3 PUFAs does not increase the risk of CYP2E1-dependent oxidative stress and diabetic liver pathology

内科学 内分泌学 氧化应激 CYP2E1 糖尿病 脂质过氧化 血脂异常 链脲佐菌素 脂肪肝 医学 多不饱和脂肪酸 抗氧化剂 化学 生物化学 新陈代谢 细胞色素P450 疾病 脂肪酸
作者
Oksana Maksymchuk,Angela Shysh,Dmytro Stroy
出处
期刊:Frontiers in Endocrinology [Frontiers Media SA]
卷期号:13 被引量:3
标识
DOI:10.3389/fendo.2022.1004564
摘要

An increase in CYP2E1 expression is a key factor in the development of diabetic oxidative liver damage. Long-term treatment with omega-3 PUFAs, which are CYP2E1 substrates, may affect CYP2E1 expression in the liver. In this work, we performed Western blot analysis, biochemical methods, and microscopic ultrastructural studies of the liver in a streptozotocin-induced rat model of type 1 diabetes to investigate whether long-term treatment with omega-3 PUFAs could induce CYP2E1-dependent oxidative stress and diabetic liver pathology. Significant hyperglycemia and lack of natural weight gain were observed in the diabetic rats compared to non-diabetic controls. A 2.5-fold increase in CYP2E1 expression (protein content and activity) was also observed in the diabetic rats. In addition, signs of oxidative stress were found in the liver of the diabetic rats. A significant increase in transaminases and GGT level in blood serum was also observed, which could indicate marked destruction of liver tissue. Diabetic dyslipidemia (increased triacylglycerol levels and decreased HDL-C levels) was found. Treatment of the diabetic animals with an omega-3-enriched pharmaceutical composition of PUFAs had no effect on CYP2E1 levels but contributed to a two-fold decrease in enzyme activity. The intensity of lipid peroxidation also remained close to the diabetic group. However, at the same time, antioxidant protection was provided by induction of antioxidant enzyme activity. Examination of the liver ultrastructure revealed no characteristic signs of diabetic pathology. However, omega-3 PUFAs did not normalize blood glucose levels and serum lipid profile. Thus, long-term treatment of diabetic rats with omega-3 PUFAs does not increase the risk of CYP2E1-dependent oxidative stress and development of liver pathology but prevents some diabetic ultrastructural damage to hepatocytes.

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