Differential toxicity of abrin in human cell lines of different organ origin

• Published in: Toxicology in vitro 2022-02, Vol.78, p.105250-105250, Article 105250
• Main Authors: Saxena, Nandita, Phatak, Pooja, Chauhan, Vinita
• Format: Article
• Language: English
• Subjects: A549 cells; Abrin; Abrin - toxicity; Abrus - chemistry; Antidotes; Bax protein; bcl-2-Associated X Protein - metabolism; Caspases - metabolism; Cell death; Cell Line - drug effects; Cell lines; Cell Survival - drug effects; Cytotoxicity; Differential sensitivity; Hep G2 cells; Humans; Ingestion; Intestine; L-Lactate Dehydrogenase - drug effects; Lethal dose; Lysosomes - drug effects; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Nervous system; Oxidation resistance; Oxidative stress; Protein biosynthesis; Protein synthesis; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reactive Oxygen Species - metabolism; Ribosomes; Ricin; Toxicity; Toxins
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2021.105250

Abrus precatorius is a highly toxic seed containing the poison abrin. Similar in properties to ricin, this toxin binds to ribosomes causing cessation of protein synthesis and cell death. With an estimated human lethal dose of 0.1–1 μg/kg, it has been the cause of fatalities due to accidental and intentional ingestion. In present study, we profiled seven human cell lines of different organ origin, for their sensitivity against abrin toxicity. These cell lines are, A549, COLO 205, HEK 293, HeLa, Hep G2, Jurkat, SH-SY5Y and derived from lung, intestine, kidney, cervix, liver, immune and nervous system respectively. MTT, NR, CVDE and LDH assays have been used to determine their response against abrin toxin. Among these cell lines A549 was the most sensitive cell line while Hep G2 was found least sensitive cell lines. Hep G2 cells are shown to have mitochondrial resistance and delayed generation of oxidative stress compared to A549 cells. Remarkable variation in sensitivity against abrin toxicity prompted the evaluation of Bcl2, Bax and downstream caspases in both cells. Difference in Bcl2 level has been shown to play important role in variable sensitivity. Findings of present study are helpful for selection of suitable cellular model for toxicity assessment and antidote screening. [Display omitted] •Abrin is potential bioweapon and many folds toxin than ricin a schedule 1 agents.•Investigations of abrin required suitable cellular model to reduce the animal usage.•Among seven cell lines, A549 was the most sensitive and Hep G2 was found to be the least sensitive cell line.•Bcl2 protein play major role in differential sensitivity.•Study may helpful for toxicity assessment and antidote screening.