Detoxifying effect of pyridoxine on acetaminophen-induced hepatotoxicity via suppressing oxidative stress injury. (April 2018)

• Record Type: Journal Article
• Authors: Roh, Taehyun; De, Umasankar; Lim, Seong Kwang; Kim, Min Kook; Choi, Seul Min; Lim, Duck Soo; Yoon, Sungpil; Kacew, Sam; Kim, Hyung Sik; Lee, Byung-Mu
• Is Part Of: Food and chemical toxicology. Volume 114(2018)
• Page Start: 11
• Page End: 22
• Publication Date: 2018-04
• Subjects: Acetaminophen -- Hepatoprotection -- Pyridoxine -- Methionine -- Betaine -- Antioxidant enzymes; AAPCC American Association of Poison Control Centers -- ALT alanine aminotransferase -- APAP acetaminophen -- ARE antioxidant response element -- AST aspartate aminotransferase -- BHMT betaine-homocysteinemethyltransferase -- CBS cystathionine β synthase -- CDNB 1-chloro-2, 4-dinitrobenzene -- DNPH 2, 4-dinitrophenylhydrazine -- DCFH-DA 2, 7-Dichlorodihydrofluorescein diacetate -- FBS fetal bovine serum -- GST glutathione S-transferase -- GSH glutathione -- GPx glutathione peroxidase -- Hcy homocysteine -- HO-1 heme oxygenase-1 -- LDH lactate dehydrogenase -- MDA malondialdehyde -- MEM minimum essential medium -- MS methionine synthase -- MTHFR methylenetetrahydrofolatereductase -- NAPQI N-acetyl-p-benzoquinoneimine -- Nrf2 nuclear factor erythroid 2-related factor 2 -- PVDF polyvinylidenedifluoride -- ROS reactive oxygen species -- SAM S-adenosylmethionine -- SAH S-adenosylhomocysteine -- SDS sodium dodecyl sulfate -- SULT sulfotransferase -- SMM S-methylmethionine -- SOD1 Cu, Zn superoxide dismutase 1 -- tHcy total homocysteine -- UGT 5′-diphospho-glucuronosyltransferase; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.02.017
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: The detoxifying effect of pyridoxine against acetaminophen (APAP)-induced hepatotoxicity was investigated. HepG2 cells were co-treated with APAP and pyridoxine to compare with betaine or methionine for 24 h. LDH, ALT and AST activities were measured to determine direct cells damage in vitro and in vivo. Lipid peroxidation, antioxidant enzymes activity, and glutathione level were measured. Cytochrome c releaseand procaspase-3, cleaved caspase-3, Bcl-2, or Bax protein levels were measured to determine APAP-induced apoptotic cell death. Pyridoxine treatment significantly increased cell viability and decreased leakage of LDH activity against APAP-induced hepatotoxicity in HepG2 cells. ALT and AST activities were dose-dependently reduced by pyridoxine treatment compared to APAP-treated group. Significant increases in activities of GST and GPx were observed after co-treatment with APAP and pyridoxine. Although APAP-induced Nrf2 and HO-1 expression levels were gradually reduced in HepG2 cells by pyridoxine treatment, induction of antioxidant enzymes activities were dose-dependently increased. These protected effects of pyridoxine against APAP-induced hepatoxicity were closely associated with suppression of APAP-induced oxidative stress and apoptotic cell death in HepG2 cells. These data indicated that the protective action of pyridoxine against hepatic cell injuries was involved in the direct antioxidant activity which provides a pivotal mechanism for its potential hepatoprotective action. Highlights: Pyridoxine decreased LDH, ALT and AST activities against APAP-induced hepatotoxicity in vitro and in vivo. Increases in antioxidant enzymes (GST and GPx) and GSH levels were observed after co-treatment with APAP and pyridoxine. Cytochrome c and procaspase-3, Bcl-2, or Bax protein levels were measured to determine APAP-induced apoptotic cell death. The protective action of pyridoxine against hepatic cell injuries was involved in the direct antioxidant activity. Pyridoxine showed protective activity via HO-1 induction serving as a key player in APAP-induced cell survival pathway.