Role of 7-chloro-4-(phenylselanyl) quinoline in the treatment of oxaliplatin-induced hepatic toxicity in mice

Can J Physiol Pharmacol. 2021 Apr;99(4):378-388. doi: 10.1139/cjpp-2020-0134. Epub 2020 Aug 18.

Abstract

There is an increasing incidence of hepatotoxicity induced by oxaliplatin (OXA); therefore, researchers' attention has been drawn to therapeutic alternatives that may decrease OXA-induced hepatotoxicity. Studies indicate that oxidative stress plays a major role in OXA-induced liver injury. As several pharmacological effects of 7-chloro-4-(phenylselanyl) quinole (4-PSQ) involve its antioxidant action, the hypothesis that this organoselenium compound could be promising for the treatment or prevention of hepatotoxicity induced by treatment with OXA was investigated. To test this hypothesis, male Swiss mice received OXA (10 mg·kg-1) on days 0 and 2, followed by oral administration of 4-PSQ (1 mg·kg-1) on days 2 to 14. 4-PSQ reduced the plasma aspartate, and alanine aminotransferase activity increased by exposure to OXA. The histopathological examination of the liver showed that 4-PSQ markedly improved OXA-induced hepatic injury. In addition, treatment with 4-PSQ reduced the oxidation of lipids and proteins (thiobarbituric acid reactive species levels and protein carbonyl content) and attenuated the increase of hepatic catalase and glutathione peroxidase activity caused by OXA. The inhibition of hepatic δ-aminolevulinic dehydratase activity induced by OXA was reverted by 4-PSQ. In conclusion, results indicate that 4-PSQ may be a good therapeutic strategy for attenuating OXA-induced liver damage.

Keywords: antioxidant; antioxydant; cancer colorectal; colorectal cancer; hepatotoxicity; hépatotoxicité; oxaliplatin; oxaliplatine; oxidative stress; quinoline; selenium; stress oxydatif; sélénium.

MeSH terms

  • Alanine Transaminase / blood
  • Alanine Transaminase / metabolism
  • Animals
  • Antineoplastic Agents / toxicity
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Catalase / metabolism
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Chemical and Drug Induced Liver Injury* / pathology
  • Chemical and Drug Induced Liver Injury* / prevention & control
  • Glutathione Peroxidase / metabolism
  • Lipid Peroxidation / drug effects
  • Liver* / drug effects
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • Mice
  • Organoplatinum Compounds / toxicity
  • Organoselenium Compounds / pharmacology
  • Organoselenium Compounds / therapeutic use
  • Oxaliplatin* / adverse effects
  • Oxaliplatin* / toxicity
  • Oxidative Stress / drug effects
  • Porphobilinogen Synthase / metabolism
  • Quinolines / pharmacology

Substances

  • Oxaliplatin
  • Quinolines
  • Antioxidants
  • Glutathione Peroxidase
  • Catalase
  • Antineoplastic Agents
  • Organoselenium Compounds
  • Organoplatinum Compounds
  • Alanine Transaminase
  • Porphobilinogen Synthase