Protective effect of diphenylmethyl selenocyanate against CCl4-induced hepatic injury

J Appl Toxicol. 2007 Nov-Dec;27(6):527-37. doi: 10.1002/jat.1230.

Abstract

Organoselenocyanates represent an important class of chemopreventive agent, which possess antioxidative, antimutagenic as well as cancer chemopreventive properties. The present study is an attempt to evaluate the protective effect of diphenylmethyl selenocyanate -- a synthetic organoselenocyanate against carbon tetrachloride (CCl(4))-induced hepatic damage in Swiss albino mice in vivo. Mice were pretreated with the Se-compound orally in a duration dependent manner (7 and 15 days) to observe its protective action against an acute toxic dose (24 h) of CCl(4) (single injection at a dose of 20 microl and 50 microl kg(-1) b.w.) that induced hepatic necrosis and caused DNA damage (strand breaks) in the hepatocytes. This study revealed that pretreatment with the Se-compound reduced the extent of massive hepatic necrosis in a duration dependent manner, but it had no modulatory effect on hepatocellular apoptosis caused by acute toxic doses of CCl(4). It was also found that the Se-compound could significantly (P < 0.01) prevent the CCl(4)-induced elevation of DNA damage in hepatocytes measured by comet assay in a duration dependent manner. So these findings will further strengthen the view that organoselenocyanate is an effective chemopreventive agent against acute hepatic damage, caused by halogenated alkanes such as CCl(4).

MeSH terms

  • Administration, Oral
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects
  • Carbon Tetrachloride
  • Comet Assay
  • DNA Damage / drug effects*
  • Disease Models, Animal
  • Female
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Massive Hepatic Necrosis / chemically induced
  • Massive Hepatic Necrosis / metabolism
  • Massive Hepatic Necrosis / pathology
  • Massive Hepatic Necrosis / prevention & control*
  • Mice
  • Organoselenium Compounds / administration & dosage
  • Organoselenium Compounds / pharmacology*
  • Organoselenium Compounds / therapeutic use
  • Oxidative Stress / drug effects
  • Time Factors

Substances

  • Antioxidants
  • Organoselenium Compounds
  • diphenylmethyl selenocyanate
  • Carbon Tetrachloride