Evaluation of the effective dose of amygdalin for the improvement of antioxidant gene expression and suppression of oxidative damage in mice

Abstract

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.

The Multiple Actions of Amygdalin on Cellular Processes with an Emphasis on Female Reproduction

“…There is a significant amount of evidence for the role of amygdalin on male reproductive functions in animals [21,22,38,43,60], as well as female reproductive system in vivo and in vitro [23,53,[61][62][63][64]. Amygdalin application positively affects ovarian cell viability and stimulates testosterone release by porcine ovarian granulosa cells; therefore, amygdalin can exert a potential effect on cellular growth and the process of ovarian steroidogenesis in vitro [62].…”

“…Taken together, the above-mentioned findings indicate the influence of amygdalin on physiological processes including female reproduction at various regulatory levels via extraand intracellular signaling pathways regulating secretory activity and steroidogenesis, as well as compromise the delicate oxidative balance in various cells and reproductive tissues (Table 2). In vivo studies 100 mg/kg/day orally 2 weeks male mice antioxidant effect positive [38] 0.6 mg/kg b.w./day i.m. 28 days male rabbits antioxidant effect positive [43] 5 mg/kg/week i.p.…”

“…Treatment time and amygdalin application type may also vary between humans and animal models. Moreover, there have been reports of cyanide toxicity due to amygdalin uses and large doses of amygdaline may cause systemic toxicity, which limits its clinical application [16,38,65].…”

“…Amygdalin-induced reactive oxygen species (ROS) production, and the subsequent benzaldehyde overproduction, may trigger protein oxidation before the lipid peroxidation process. Although low and medium doses (50 and 100 mg/kg) of orally administered amygdalin induce no toxicity in mice, amygdalin at a high dose (200 mg/kg) is capable of inducing toxicity and exerts negative effects on the oxidative balance of hepatic tissues with an obvious effect on the histopathology in mice [ 38 ].…”

“…Natural substances and alternative medications such as amygdalin gained huge popularity in treating various diseases due to their wide availability and relatively low cost [ 6 ]. Numerous previous studies have documented that amygdalin has antibacterial, anti-inflammatory, and immunoregulatory activities, as well as improves the immune function of organism, and affects oxidative balance [ 25 , 38 , 47 , 48 , 49 ].…”