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

被引:6
|
作者
Saxena, Nandita [1 ]
Phatak, Pooja [1 ]
Chauhan, Vinita [2 ]
机构
[1] Def Res Dev Org, Div Pharmacol & Toxicol, Def Res Dev & Estab, Gwalior 474002, Madhya Pradesh, India
[2] Def Res Dev Org, Biotechnol Div, Def Res Dev & Estab, Gwalior 474002, Madhya Pradesh, India
关键词
A549; cells; Abrin; Cytotoxicity; Differential sensitivity; Hep G2 cells; Ricin; BCL-2 FAMILY PROTEINS; OXIDATIVE STRESS; LECTINS ABRIN; RICIN; DEATH; APOPTOSIS; PATHOGENESIS; HEPATOCYTES; METABOLISM; EXPRESSION;
D O I
10.1016/j.tiv.2021.105250
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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 mu g/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.
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页数:11
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