Background Little is known regarding the toxic and therapeutic doses of amygdalin. Treatment regimens and schedules can vary between humans and animal models, and there have been reports of cyanide toxicity due to amygdalin use. Objective The aim of this study was to evaluate the effect of different doses of amygdalin on antioxidant gene expression and suppression of oxidative damage in mice. Methods Forty adult male mice were divided randomly into four groups (n = 10) as follows and treated orally for two weeks: a control group treated with saline solution, a group treated with amygdalin at 200 mg/kg body weight, a group treated with amygdalin at 100 mg/kg body weight, and a group treated with amygdalin at 50 mg/kg body weight. Liver and testis samples were collected for gene expression, biochemical and histopathological analyses. Results The mice treated with medium-dose amygdalin (100 mg/kg) showed upregulated mRNA expression of glutathione peroxidase (P < 0.01) and superoxide dismutase (P < 0.05) and significantly decreased lipid peroxidation (P < 0.05) in hepatic and testicular tissues compared to those in the untreated groups (controls), with mild histopathological effects. The mice treated with high-dose of amygdalin (200 mg/kg) showed downregulated mRNA expression of glutathione peroxidase and superoxide dismutase (P < 0.01) and significantly increased lipid peroxidation (P < 0.05) in both hepatic and testicular tissues compared to those in the untreated groups (controls), with an apparent effect at the histopathological level. No effects were observed in the mice treated with low-dose amygdalin (50 mg/kg) at the gene, protein and histopathological level. Conclusion Low-and medium-dose amygdalin did not induce toxicity in the hepatic and testicular tissues of male mice, unlike high-dose amygdalin, which had a negative effect on oxidative balance in mice. Therefore, amygdalin at a moderate dose may improve oxidative balance in mice.

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