Diosmin exerts hepatoprotective and antihyperglycemic effects against sodium arsenite-induced toxicity through the modulation of oxidative stress and inflammation in mice.

BACKGROUND

Chronic exposure to high concentrations of inorganic arsenic (NaAsO) in drinking water is related to an increase in the risk of liver toxicity and diabetes. Diosmin has various pharmacological properties, including antioxidant and anti-inflammatory properties. This study was designed to investigate the protective effects of diosmin on diabetes and hepatotoxicity caused by NaAsO.

METHODS

Sixty male 8-week-old NMRI mice, weighing 25 ± 2 g, were randomly selected and put into six groups. The control (Group 1) was treated orally with distilled water, group 2 was treated with diosmin (100 mg/kg, p.o), group 3 received NaAsO (10 mg/kg, p.o), and groups 4, 5, 6 received diosmin (25, 50, 100 mg/kg, p.o), respectively and NaAsO (10 mg/kg, p.o). After 29 days, fasting blood sugar (FBS) measurement and glucose tolerance test were done. The mice were sacrificed on day 31, and blood and tissue (liver and pancreas) samples were taken. Then, serum and tissue samples were studied for biochemical and histological evaluations.

RESULTS

The results demonstrated that diosmin ameliorated glucose intolerance and decreased FBS compared to the NaAsO group. Diosmin (50 and 100 mg/kg) improved the serum factors of liver function (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) in the groups receiving NaAsO. Moreover, increased levels of nitric oxide, tumor necrosis factor-alpha, and thiobarbituric acid reactive substances in liver tissue induced by NaAsO were diminished by diosmin treatment. Administration of diosmin increased total thiol and enzymatic activities of catalase, superoxide dismutase, and glutathione peroxidase in liver tissue. Furthermore, treatment with diosmin reduced the increase in protein amount of Sirtuin 3 and nuclear factor kappa B in the groups receiving NaAsO. Also, the liver and pancreas histological lesions induced by NaAsO were attenuated by diosmin treatment.

CONCLUSION

Diosmin has a preventive effect against hepatotoxicity and diabetes induced by NaAsO in mice through its antioxidant and anti-inflammatory properties.