Salicylic acid-induced hepatotoxicity triggered by oxidative stress

Chemico-biological Interactions
Hirokazu Doi, Toshiharu Horie

Abstract

Salicylic acid is a widely used nonsteroidal anti-inflammatory drug (NSAID). But it is known to cause serious liver damage occasionally. Mitochondrial dysfunction and oxidative stress are predicted to be the major factors of salicylic acid-induced liver injury. We investigated the influence of salicylic acid on ATP contents, oxygen consumption and lipid peroxidation in the presence of the same concentration of salicylic acid. Leakage of lactate dehydrogenase (LDH) was significantly higher in the presence of 5mM salicylic acid than in its absence. Salicylic acid-induced thiobarbituric acid-reactive substance (TBARS) formation and spontaneous chemiluminescence (CL) in rat hepatocytes, whereas antioxidants, such as promethazine (PMZ) and N,N-diphenylphenylenediamine (DPPD), suppressed both TBARS formation and LDH leakage. TBARS formation in rat liver microsomes was suppressed by diethyldithiocarbamate (a specific inhibitor of cytochrome P450 (CYP)2E1) and diclofenac (a specific inhibitor of CYP2C11). These results suggest that salicylic acid-induced lipid peroxidation was related to oxidative metabolism mediated by CYP2E1 and CYP2C11. On the other hand, 5mM salicylic acid induced a drastic decrease of ATP contents in rat isolated ...Continue Reading

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Citations

Nov 10, 2012·BMC Pharmacology & Toxicology·Yoshinori InagakiKazuhisa Sekimizu
Dec 4, 2010·World Journal of Gastroenterology : WJG·Fernando Bessone
Oct 11, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Yong-Song Guan, Qing He
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Feb 2, 2020·The Science of the Total Environment·Rosa FreitasCaterina Faggio
Jun 22, 2021·Journal of Water and Health·Sabrine AfsaHedi Ben Mansour

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