Effect of alpha-lipoic acid on antioxidant gene expression and kidney injury in alloxan-induced diabetic rats

Parisa Jamor,Hassan Ahmadvand,Hesam Ashoory,Esmaeel Babaeenezhad

doi:10.15171/jnp.2019.06

Parisa Jamor, Hassan Ahmadvand + Show 2 more

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https://doi.org/10.15171/jnp.2019.06

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Abstract

Background: Myeloperoxidase (MPO) is involved in the initiation, progression, and complications of atherosclerosis in diabetic patients. Objectives: In the current study, the impact of alpha-lipoic acid (LA), a natural antioxidant and a cofactor in the enzyme complexes on MPO, catalase (CAT) and glutathione peroxidase (GPx) activity, glutathione (GSH) and malondialdehyde (MDA) level, histopathology of kidney and expression of antioxidant enzymes, superoxide dismutase (SOD), GPx and CAT which are involved in the detoxification of reactive oxygen species (ROS), was evaluated in alloxan-induced diabetic rats. Materials and Methods: In this study, 30 male Rattus norvegicus rats randomly divided into three groups; control (C), non-treated diabetic (NTD), and LA-treated diabetics (LATD) was induced by alloxan monohydrate (100mg/kg; subcutaneous [SC]). Then treatment was performed with alphaLA (100 mg/kg intraperitoneal (i.p) daily to 6 weeks). Blood sample of animals collected to measure levels of MPO, CAT and GPx activity GSH and MDA. Kidney paraffin sections were prepared to estimate histological studies and to measure quantitative gene expression SOD, GPX and CAT in kidney. Results: Induction of diabetes led to a significant increase in MPO and MDA, reduced GSH level and GPx and CAT activities (P < 0.05). However, treatment with alpha-LA led to a significant elevation in GPx, CAT and GSH levels with a reduction in MPO activities and MDA levels (P < 0.05). Furthermore, the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis results showed increased expressions of GPx, CAT and SOD enzyme in the treatment group compared with the diabetic control group. Histopathological lesions such as increased glomerular volume and lymphocyte infiltration were attenuated in the alpha-LA treated group. Conclusions: Our findings indicated that alpha-LA supplementation is effective in preventing complications induced by oxidative stress and atherosclerosis in diabetic rats.

Highlights

Myeloperoxidase (MPO) is involved in the initiation, progression, and complications of atherosclerosis in diabetic patients
Biochemical markers The activities of enzymatic antioxidants such as CAT, and glutathione peroxidase (GPx) in the serum, liver and kidney of control and experimental groups of rats are presented in Tables 2 and 3 respectively
The activities of CAT and GPx significantly decreased in the serum, liver and kidney of diabetic control group compared with normal control rats

Summary

Introduction

Myeloperoxidase (MPO) is involved in the initiation, progression, and complications of atherosclerosis in diabetic patients. Results: Induction of diabetes led to a significant increase in MPO and MDA, reduced GSH level and GPx and CAT activities (P < 0.05). The real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis results showed increased expressions of GPx, CAT and SOD enzyme in the treatment group compared with the diabetic control group. Histopathological lesions such as increased glomerular volume and lymphocyte infiltration were attenuated in the alpha-LA treated group.

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