Effects of carnosine, taurine, and betaine pretreatments on diethylnitrosamine-induced oxidative stress and tissue injury in rat liver

Toxicol Ind Health. 2016 Aug;32(8):1405-1413. doi: 10.1177/0748233714563432. Epub 2014 Dec 31.

Abstract

Several chemicals such as N-diethylnitrosamine (DEN) promote hepatocellular cancer in rodents and induce hepatocyte injury. DEN affects the initiation stage of carcinogenesis together with enhanced cell proliferation accompanied by hepatocellular necrosis. DEN-induced hepatocellular necrosis is reported to be related to enhanced generation of reactive oxygen species. Carnosine (CAR), taurine (TAU), and betaine (BET) are known to have powerful antioxidant properties. We aimed to investigate the effects of CAR, TAU, and BET pretreatments on DEN-induced oxidative stress and liver injury in male rats. Rats were given CAR (2 g L-1 in drinking water), TAU (2.5% in chow), and BET (2.5% in chow) for 6 weeks and DEN (200 mg kg-1 intraperitoneally) was given 2 days before the end of this period. Serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and γ-glutamyl transferase activities were determined and a histopathologic evaluation was performed on the liver tissue. Oxidative stress was detected in the liver by measuring malondialdehyde, diene conjugate, protein carbonyl and nitrotyrosine levels, glutathione and glutathione peroxidase levels, and superoxide dismutase and glutathione transferase activities. Pretreatments with CAR, TAU, and BET decreased liver prooxidant status without remarkable changes in antioxidant parameters in DEN-treated rats. Pretreatments with TAU and BET, but not CAR, were also found to be effective to reduce liver damage in DEN-treated rats. In conclusion, TAU, BET, and possibly CAR may have an ameliorating effect on DEN-induced hepatic injury by reducing oxidative stress in rats.

Keywords: Hepatic injury; betaine; carnosine; diethylnitrosamine; oxidative stress; taurine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Betaine / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Carcinogens, Environmental / administration & dosage
  • Carcinogens, Environmental / chemistry
  • Carcinogens, Environmental / toxicity
  • Carnosine / therapeutic use
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Dietary Supplements*
  • Diethylnitrosamine / administration & dosage
  • Diethylnitrosamine / antagonists & inhibitors*
  • Diethylnitrosamine / toxicity
  • Glutathione / agonists
  • Glutathione / antagonists & inhibitors
  • Glutathione / metabolism
  • Injections, Intraperitoneal
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver / physiopathology
  • Male
  • Oxidative Stress / drug effects*
  • Protein Carbonylation / drug effects
  • Random Allocation
  • Rats, Wistar
  • Taurine / therapeutic use*
  • Tyrosine / analogs & derivatives
  • Tyrosine / antagonists & inhibitors
  • Tyrosine / metabolism

Substances

  • Antioxidants
  • Biomarkers
  • Carcinogens, Environmental
  • Taurine
  • 3-nitrotyrosine
  • Diethylnitrosamine
  • Betaine
  • Tyrosine
  • Carnosine
  • Glutathione