Laboratory aspects of phallacidin toxic effects on rats

Abstract

Background: This study reviewed the hematological and biochemical changes in phallacidin-intoxicated outbred rats and their potential roles in thanatogenesis. The established laboratory correlates of phallacidin intoxication are inconsistent and controversial, indicating an understudied toxicity produced by this peptide. Therefore, hematological and biochemical changes in rats associated with extremely severe phallacidin intoxication should be assessed at three median lethal doses (6.3 mg/kg).

Materials and methods: This two-stage study included 27 outbred male rats weighing 300–350 g. In stage 1, postmortem changes in complete blood count and blood chemistry were examined, whereas during stage 2, changes in plasma hemoglobin and glucose concentrations at different time points after peptide administration were evaluated. The toxic effects of phallacidin at three median lethal doses (6.3 mg/kg) following intraperitoneal administration is associated with severe intoxication with 100% mortality within 5 hours.

Results: The animals developed myoplegia, coma, moderate seizures manifested as pawing-type periodic clonus of the forelimbs, fulminant hepatic failure with cytolysis, cholestasis, hypoglycemia, and hemorrhage in the liver tissue with massive blood loss accompanied by consumptive thrombocytopenia. Visual examination of the dead rats revealed pale mucous membranes of the nasal and oral cavities and skin of the ears and tail. Skeletal muscle spasm was observed in rats who experienced seizures. Urgent hypoglycemia was established as the immediate cause of rat mortality. Hypoglycemia was related to seizures and occurred before onset and severity of the concurrently massive hemorrhage.

Conclusions: Thus, сarbohydrate metabolism disorders in phallacidin intoxication determine the condition severity and time of death in rats, whereas blood loss events potentiate сarbohydrate metabolism disorders. The mechanisms of hypoglycemia in rats and neurologic impairment in a short time require a more detailed review.

Keywords

hepatotoxicity / hypoglycemia / hemorrhage / blood loss / thanatogenesis / fungal toxins / phallacidin / phallotoxins / fulminant hepatic failure / cholestasis / cytolysis

References

[1] Pospich S, Merino F, Raunser S. Structural effects and functional implications of phalloidin and jasplakinolide binding to actin filaments. Structure. 2020;28(4):437–449. EDN: HZIQMY doi: 10.1016/j.str.2020.01.014

[2] Walton J. The cyclic peptide toxins of Amanita and other poisonous mushrooms. Cham: Springer; 2018. 231 р. EDN: VIKTEQ doi: 10.1007/978-3-319-76822-9

[3] Khovpachev AA, Basharin VA, Chepur SV, et al. experimental evaluation of the hemodynamic effects of allacidin using transpulmonal thermodilution and arteriovenous blood gas gradient. Russian Biomedical Journal. 2023;24(1):542–559. EDN: FLGBYI

[4] Racine R. Modification of seizure activity by electrical stimulation: II Motor seizure. Electroenc Clin Neurophysiol. 1972;3(32):281–294. doi: 10.1016/0013-4694(72)90177-0

[5] Ivanov IM, Nikiforov AS, Trofimova VS, et al. Comparative research of effects of permeability enhancers on the effectiveness of model protein (insulin) administered via the inhalation route. Medicо-Biological and Socio-Psychological Problems of Safety in Emergency Situations. 2018;4:76–83. EDN: VSTTCW doi: 10.25016/2541-7487-2018-0-4-76-83. (In Russ.)

[6] Koptyaeva KE, Muzhikyan AA, Gushchin YaA, et al. Technique of dissection and extracting organs of laboratory animals. Message 1 (rats). Laboratory animals for scientific research. 2018;(2):71–92. EDN: XSMTCH doi: 10.29296/10.29296/2618723X-2018-02-08

[7] Melnikova NN. Effect of systemic hypothermia on reactions of pial arteries to acute massive blood loss in anesthetized rats. J Evol Biochem Physiol. 2022;58(5):380–390. EDN: AAUVHT doi: 10.31857/S0044452922050084

[8] Ministry of Health of the Russian Federation, Federal Medical and Biological Agency. Modeling of intoxications with depriming agents and assessment of the severity of the depriming effect. Moscow; 2013. 31 p. (In Russ.)

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