Dermal absorption and toxicity of alpha amanitin in mice

Abstract

The fungus Amanita phalloides is known to contain two main groups of toxins: amanitins and phallotoxins. The amanitins group effectively blocks the RNA polymerase II enzyme found in eukaryotic cells. As alpha amanitin has a lethal effect on the majority of eukaryotic cells, it can be valuable as an antiparasitic or antifungal drug. It can be used externally against ectoparasites. It is critical that percutaneous applications of the alpha amanitin toxin are not harmful to the recipient. In this study, the absorption and the toxicity of percutaneous and intraperitoneal (ip) applications of 1 mg/kg alpha amanitin to mice were compared. Potential skin, liver and kidney toxicities were investigated through pathological examination. HPLC analysis was used to determine the amount of the toxin. No toxicity or toxin were found in the skin, liver, or kidneys of the mice in the control group. Interestingly, the percutaneous application group also showed no toxicity, and the toxin was not present in this group. After 24 h, Councilman-like bodies and pyknotic cells were observed in the mice in which alpha amanitin was applied intraperitoneally, demonstrating the presence of toxicity. Peak levels of alpha amanitin (µg/mL) in the liver, kidney, and blood in the ip application group were measured at 3.3 (6 h), 0.2 (6 h) and 1.2 (1 h), respectively. The results demonstrated that the toxin was not absorbed through the skin of the mice and that the percutaneous application of alpha amanitin did not have any toxic effects. Thus, alpha amanitin may be administered percutaneously for therapeutic purposes.

A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

“…The liver of mice administered with α-amanitin evidenced severe damage, with cellular edema, cytoplasmic vacuolization, and interstitial inflammatory cell infiltration, as well as some centrilobular necrotic zones. These histological phenotypes are in agreement with previous reports of α-amanitin studies in mice (Kaya et al 2014;Wills et al 2005;Zhao et al 2006). α-Amanitin (1 mg/kg i.p.…”

“…α-Amanitin (1 mg/kg i.p. )-treated Balb/c mice showed vacuolar degeneration of liver cells, 1 and 6 h after poisoning (Kaya et al 2014), whereas α-amanitin (0.327 mg/kg intravenous) caused liver fatty degeneration and necrosis 48 h after treatment in the same mice strain (Zhao et al 2006). Moreover, histopathological hepatic damage in laboratory animals is similar to that found in humans after A. phalloides intoxication, namely regarding features of hepatic massive centrilobular necrosis and vacuolar degeneration (Fineschi et al 1996).…”

Amanita phalloides poisoning: Mechanisms of toxicity and treatment

“…Moreover, dogs and humans share a great oral bioavailability for amatoxins (Faulstich et al, 1985). Despite the scarce oral bioavailability in rodents, the toxic effects of amatoxins are similar to those found in humans (Kaya et al, 2014). Most studies with mice use intraperitoneal administration that could intensify the amatoxins-induced organ damage.…”

Discovery of an effective antidote for Amanita phalloides poisoning

“…Moreover, dogs and humans share a great oral bioavailability for amatoxins (45). Despite the scarce oral bioavailability in rodents, the toxic effects of amatoxins are similar to those in humans (102). Most in mice studies use intraperitoneal administration that could intensify the amatoxins-induced organ damage.…”