Abstract
Epidemiological evidence has associated chronic exposure to inorganic arsenic with an increased occurrence of glucose intolerance and diabetes mellitus. Furthermore, inorganic arsenic induces oxidative stress in organs such as the liver. Betaine, as a methyl donor, plays a pivotal role in homocysteine metabolism. Betaine has antioxidant and anti-inflammatory properties. Therefore, the aim of this study was to evaluate the effects of betaine against sodium arsenite-induced diabetes and hepatotoxicity in mice. Forty-eight male mice were divided into 6 groups of 8. Group 1, received distilled water every day for 4 weeks by gavage. Group 2 received 500 mg/kg betaine every day for 4 weeks by gavage. Group 3 was given 10 mg/kg NaAsO2 every day for 4 weeks by gavage. Groups 4, 5, and 6 were co-treated with 125, 250, and 500 mg/kg betaine half an hour before NaAsO2 (10 mg/kg), respectively, daily for up to 4 weeks by gavage. After 28 days of the study, the mice were fasted overnight and on day 29, fasting blood glucose was measured and glucose tolerance test was performed. On day 30, the mice were anesthetized and a blood sample was taken from the heart. Serum factors (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase activities), oxidative stress factors (malondialdehyde and glutathione levels, and the activity of superoxide dismutase, glutathione peroxidase, and catalase enzymes) and hepatic inflammatory factors (nitric oxide and tumor necrosis factor α) were measured. Histopathological studies were also performed on the liver and pancreas. In this study, it was shown that arsenic causes glucose intolerance, and oxidative/inflammatory hepatic damage. Co-administration of betaine prevents hepatotoxicity and glucose intolerance induced by arsenic in mice. Co-treatment of betaine with arsenic improved glucose intolerance and protected the liver against arsenic induced-oxidative damage and inflammation. Betaine at the dose of 500 mg/kg showed better results than the other doses. Accordingly, betaine can be suggested as a therapeutic agent against diabetogenic and hepatotoxic effects of arsenic.
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The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We are grateful for all the support given by the technicians at the Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Thanks go to the Department of Toxicology, especially Seyed Mohamad Nokhbe for animal handling and helping.
Funding
This paper is issued from the Pharm.D thesis of Parian Pourmoafi Esfahani and was financially supported by the Toxicology Research Center (Grant number; TRC-9908) of the Ahvaz Jundishapur University of Medical Sciences.
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MJK and MM: study concept and design, critical revision of the manuscript for important intellectual content.
LK and PPE: acquisition of data, analysis, and interpretation of data.
MR and HN: administrative, technical, and material supports, drafting of the manuscript.
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Esfahani, P.P., Mahdavinia, M., Khorsandi, L. et al. Betaine protects against sodium arsenite-induced diabetes and hepatotoxicity in mice. Environ Sci Pollut Res 30, 10880–10889 (2023). https://doi.org/10.1007/s11356-022-22941-w
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DOI: https://doi.org/10.1007/s11356-022-22941-w