Hamed Haghi Aminjan1, Seyed Reza Abtahi1, Ebrahim Hazrati2, Mohsen Chamanara1, Maryam Jalili3, Babak Paknejad4. 1. Department of Pharmacology and Toxicology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran. 2. Department of Anesthesia and Intensive Care, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran. 3. Department of Clinical Sciences, School of Veterinary, Shiraz University, Shiraz, Iran. 4. Department of Pharmacology and Toxicology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran. Electronic address: Drpakb@yahoo.com.
Abstract
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
Authors: Mehdi Sharifi-Rad; Nanjangud V Anil Kumar; Paolo Zucca; Elena Maria Varoni; Luciana Dini; Elisa Panzarini; Jovana Rajkovic; Patrick Valere Tsouh Fokou; Elena Azzini; Ilaria Peluso; Abhay Prakash Mishra; Manisha Nigam; Youssef El Rayess; Marc El Beyrouthy; Letizia Polito; Marcello Iriti; Natália Martins; Miquel Martorell; Anca Oana Docea; William N Setzer; Daniela Calina; William C Cho; Javad Sharifi-Rad Journal: Front Physiol Date: 2020-07-02 Impact factor: 4.566
Authors: Michael J Daseke; Upendra Chalise; Mediha Becirovic-Agic; Jeffrey D Salomon; Leah M Cook; Adam J Case; Merry L Lindsey Journal: Cell Signal Date: 2020-10-24 Impact factor: 4.315