Tetrachlorobenzoquinone induces acute liver injury, up-regulates HO-1 and NQO1 expression in mice model: the protective role of chlorogenic acid

Environ Toxicol Pharmacol. 2014 May;37(3):1212-20. doi: 10.1016/j.etap.2014.04.022. Epub 2014 Apr 26.

Abstract

Tetrachlorobenzoquinone (TCBQ) is an active metabolite of pentachlorophenol (PCP). Although PCP has been investigated extensively, there are only a few reports describing the toxicity effect of TCBQ, and no report regarding TCBQ-induced liver injury in vivo. In the current study, we aimed to examine the acute hepatic toxicity of TCBQ in the mice model. Chlorogenic acid (CGA) exhibits promising antioxidant activity in the past studies, thus, the second aim of this study was to evaluate the protective effect of CGA on TCBQ-induced liver injury. Our results indicated TCBQ-intoxication caused marked liver cell necrosis and inflammation but not apoptosis, and this damage was alleviated by CGA treatment. Meantime, TCBQ-intoxication enhanced serum ALT, AST activities, TBIL content, hepatic oxidative stress and lipid peroxidation, decreased GSH content and inhibited the activities of antioxidant enzymes. Western blot and immunohistochemical analysis showed that TCBQ marked up-regulated HO-1 and NQO1 expression. On the other hand, pretreatment of CGA reduced TCBQ-induced liver damage remarkably. Taking together, these results revealed that TCBQ has strong hepatic toxic effect, and at least a part of this effect is initiated by free radical and relieved with CGA administration.

Keywords: Chlorogenic acid; HO-1; NQO1; Oxidative stress; Tetrachlorobenzoquinone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Catalase / metabolism
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chloranil / toxicity*
  • Chlorogenic Acid / pharmacology
  • Chlorogenic Acid / therapeutic use*
  • Fungicides, Industrial / toxicity*
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Heme Oxygenase-1 / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism
  • Up-Regulation

Substances

  • Antioxidants
  • Fungicides, Industrial
  • Membrane Proteins
  • Reactive Oxygen Species
  • Chloranil
  • Chlorogenic Acid
  • Catalase
  • Glutathione Peroxidase
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Superoxide Dismutase
  • NAD(P)H Dehydrogenase (Quinone)
  • Nqo1 protein, mouse
  • Glutathione Reductase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione