Toxicity and urinary metabolites of α-amanitin in mice

  Objective  To explore toxicity and urinary metabolites of α-amanitin in mice with a 21-day toxicological experiment.

  Methods  Twenty ICR male mice were randomly divided into a control (n = 5) and three median lethal dose (LD₅₀) groups (5 in each group) with a single intraperitoneal injection of α-amanitin at doses of 0.25, 0.35, and 0.5 mg/kg·bw. Daily urine excretion of the mice was collected from 1st to 7th day after the injection for detection of toxins with liquid chromatography-mass spectrometry. Poisoning symptoms, body weight, and death of the mice were recorded during the 21-day experiment. By the end of the observation, all mice were sacrificed for determinations of liver/kidney weight and organ coefficient, blood biochemical indicators and pathological examination.

  Results  Urinary α-amanitin was detected in all mice of dose groups for 4 days after the toxic treatment and the urinary excretion of α-amanitin in the 1st day accounted for 67.00 % – 98.35% of total urinary excretion within 7 days after the intoxication. Six deaths were observed in the mice of dose groups from 3rd to 10th day after the toxic treatment. Compared to those in the control mice, significantly decreased kidney weight (0.48 ± 0.05 vs. 0.59 ± 0.05 g) and coefficient (1.35 ± 0.11% vs. 1.49 ± 0.09%) but increased serum creatinine (18.25 ± 8.80 vs. 11.30 ± 7.60 µmol/L) and alkaline phosphatase (111.50 ± 32.30 vs. 78.00 ± 13.20 U/L) were detected in the surviving mice of dose groups at the end of experiment (P < 0.05 for all); kidney pathological changes of the surviving mice were also observed mainly in renal cortex, including renal tubular lesion and a large amount of protein cast.

  Conclusion  In mice, urinary excretion of α-amanitin could be detected in the early intoxication stage (1st – 4th day) and kidney injury is a main toxic effect in late stage of intoxication.