Alpha-Amanitin Poisoning, Nephrotoxicity and Oxidative Stress: An Experimental Mouse Model

Abstract

Background:Alpha-amanitin (α-AMA) plays a major role in Amanita phalloides poisoning, showing toxic effects on multi-organs, particularly on the liver and kidneys. Studies have shown a relationship between α-AMA-related injuries and reactive oxygen species.Objectives:We aimed to investigate whether there is renal injury and its relationship with oxidative stress after intraperitoneal injection of α-AMA in mice experimental poisoning models.Materials and Methods:There were 37 male BALB/c laboratory mice treated with α-AMA, according to the study groups: control group (n = 7); low dose (0.2 mg/kg) (n = 10); moderate dose (0.6 mg/kg) (n = 10), and high dose (1 mg/kg) (n = 10). The sample size was detected according to the ethical committee’s decision as well as similar studies in the literature. After a 48-hour follow-up period, all the subjects were sacrificed for pathological and biochemical assays. The study was held in Turkey.Results:α-AMA poisoning in mice results in inflammatory changes and necrosis in renal structures. There were statistically significant differences between the study groups regarding measured levels of catalase, superoxide dismutase, glutathione peroxidase, total antioxidant status (TAS), total oxidant status (TOS) and malonyl dialdehyde in renal homogenates of mice (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.001, respectively). The TOS and TAS measurements helped to eliminate cumbersome analysis of diverse oxidant and antioxidant molecules. The TOS levels in renal homogenate of mice were significantly higher in all the intoxication groups compared to the control group (5.73, 7.02, 7.77, and 9.65 mmol trolox eq/g protein and P = 0.002, P = 0.001, and P = 0.001, respectively). The TAS levels in moderate and high-dose groups were significantly lower than all the other groups treated with α-AMA (0.130, 0.152, 0.065, and 0.087 mmol trolox eq/g protein and P = 0.031, P = 0.001, and P = 0.001, respectively).Conclusions:Our results indicated that α-AMA poisoning in mice led to inflammatory changes and necrosis in renal structures. Biochemical analysis showed a shift in the oxidative/anti-oxidative balance towards the oxidative status.

A Comparison of the Effectiveness of Silibinin and Resveratrol in Preventing Alpha‐Amanitin‐Induced Hepatotoxicity

“…Ergin et al . observed no mortality in mice at 48 hr with any of the increasing doses of α‐AMA administered, showing that the LD 50 can change under varying conditions .…”

Toxicological profile of Amanita virosa – A narrative review

“…Ingestion of toxin-containing Amanita mushrooms leads to challenging hepatotoxicity although additional disturbances like allergic gastroenteritis may also result [14,24,52,[75], [76], [77]]. Interestingly, nephrotoxic effects were also demonstrated in different studies [33,[78], [79], [80], [81]], which may have an important impact on the renal excretion of absorbed toxins. Therefore, the final observed clinical toxicity is related to the type and amount of ingested mushrooms, i.e.…”

Effects of resveratrol on alpha-amanitin-induced nephrotoxicity in BALB/c mice

“…18 All injections were administered intraperitoneally, as in previous studies. 6,7,[15][16][17][18][19][20] At the end of the 48 h, mice were euthanized under ether anesthesia.…”

“…Studies have determined oxidative stress and inflammation as the main mechanisms of a-AMA-induced nephrotoxicity. [6][7][8][9][10][11] Silibinin exerts antidote effect against A. phalloides poisoning by acting as an OATP1 inhibitor. Although penicillin G has been used as an alternative antidote to silibinin, there is no strong evidence of its effectiveness against mushroom poisonings.…”