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Targeting of oxidative stress and inflammation through ROS/NF-kappaB pathway in phosphine-induced hepatotoxicity mitigation

Haghi Aminjan, Hamed, Abtahi, Seyed Reza, Hazrati, Ebrahim, Chamanara, Mohsen, Jalili, Maryam, Paknejad, Babak
Life sciences 2019 v.232 pp. 116607
NADP-glucose-6-phosphate dehydrogenase, aluminum, apoptosis, blood serum, catalase, dose response, heart, hepatocytes, hepatotoxicity, histology, inflammation, intercellular adhesion molecule-1, interleukin-1beta, interleukin-6, kidneys, lethal dose 50, liver, mortality, necrosis, oxidative stress, phosphides, phosphine, phosphorylation, poisoning, rats, resveratrol, signal transduction, superoxide dismutase, transcription factor NF-kappa B, tumor necrosis factor-alpha
Poisoning with aluminium phosphide (AlP) commonly has a high rate of mortality and morbidities. Phosphine gas is the main cause of AlP poisoning that has deleterious effect on multi-organs especially heart, kidney, and liver. Furthermore, several studies reported that resveratrol has cytoprotective effects through its pleiotropic property. The purpose of this study was to estimate the dose-dependent role of resveratrol on phosphine induced acute hepatic toxicity in rat model.The rats have been exposed to LD50 of AlP (12 mg/kg) by gavage, and resveratrol doses (20, 40, and 80 mg/kg) were injected 30 min after intoxication. After 24 h, the serum and liver tissue were collected for present study.The results indicated that phosphine causes an alteration in oxidative stress markers including elevation of ROS, and GSH level, MPO activity, reduction in SOD, catalase and G6PD activity as well as reduction in SOD1 and catalase expression. Furthermore, phosphine significantly induced phosphorylation of IkappaB, NF-kappaB and up-regulation of TNF-α, IL-1β, IL-6, and ICAM-1 expression. Also, phosphine induces markedly reduced hepatocytes lives cell and elevated apoptosis and necrosis. Co-treatment of resveratrol in a dose-dependent manner reversed aforementioned alterations. All in all, histological analysis indicated a deleterious effect of phosphine on the liver, which is mitigated by resveratrol administration.The results of the present study suggest targeting ROS/NF-kappaB signalling pathway by resveratrol may have a significant effect on the improvement of hepatic injury induced by phosphine. It also may be a possible candidate for the treatment of phosphine-poisoning.