Protective effects of L-carnosine on CCl4 -induced hepatic injury in rats

Eur Cytokine Netw. 2016 Mar 1;27(1):6-15. doi: 10.1684/ecn.2016.0372.

Abstract

The present study was undertaken to investigate the possible protective effect of L-carnosine (CAR), an endogenous dipeptide of alanine and histidine, on carbon tetrachloride (CCl4)-induced hepatic injury. Liver injury was induced in male Sprague-Dawley rats by intraperitoneal (i.p.) injections of CCl4, twice weekly for six weeks. CAR was administered to rats daily, at dose of 250 mg/kg, i.p. At the end of six weeks, blood and liver tissue specimens were collected. Results show that CAR treatment attenuated the hepatic morphological changes, necroinflammation and fibrosis induced by CCl4, as indicated by hepatic histopathology scoring. In addition, CAR treatment significantly reduced the CCl4-induced elevation of liver-injury parameters in serum. CAR treatment also combatted oxidative stress; possibly by restoring hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) levels. Moreover, CAR treatment prevented the activation of hepatic stellate cells (HSCs), as indicated by reduced α-smooth muscle actin (α-SMA) expression in the liver, and decreased hepatic inflammation as demonstrated by a reduction in hepatic tumor necrosis factor-α (TNF-α) and restoration of interleukin-10 (IL-10) levels. In conclusion, CCl4-induced hepatic injury was alleviated by CAR treatment. The results suggest that these beneficial, protective effects are due, at least in part, to its anti-oxidant, anti-inflammatory and anti-fibrotic activities.

Keywords: CCl4-induced hepatic injury; Nrf2; carnosine; α-SMA.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Biomarkers
  • Carbon Tetrachloride / adverse effects*
  • Carnosine / pharmacology*
  • Carnosine / therapeutic use
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / pathology*
  • Disease Models, Animal
  • Gene Expression
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Liver Cirrhosis
  • Liver Function Tests
  • Male
  • Models, Biological
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Nitric Oxide / metabolism
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use
  • Rats
  • Superoxide Dismutase / metabolism

Substances

  • Actins
  • Biomarkers
  • NF-E2-Related Factor 2
  • Protective Agents
  • Nitric Oxide
  • Carnosine
  • Carbon Tetrachloride
  • Superoxide Dismutase