Role of mammalian cytosolic molybdenum Fe-S flavin hydroxylases in hepatic injury.

Abstract

The study was designed to investigate the role of molybdenum iron-sulfur flavin hydroxylases in the pathogenesis of liver injuries induced by structurally and mechanistically diverse hepatotoxicants. While carbon tetrachloride (CCl4), thioacetamide (TAA) and chloroform (CHCl3) inflict liver damage by producing free radicals, acetaminophen (AAP) and bromobenzene (BB) exert their effects by severe glutathione depletion. Appropriate doses of these compounds were administered to induce liver injury in rats. The activities of the Mo-Fe-S flavin hydroxylases were measured and correlated with the biochemical markers of hepatic injury. The activity levels of the anti-oxidative enzymes and glutathione redox cycling enzymes were also determined. The treatment of rats with the hepatotoxins that inflict liver injury by generating free radicals (CCl4, TAA, CHCl3) had elevated activity levels of hepatic Mo-Fe-S flavin hydroxylases (p<0.05). Specific inhibition of these hydroxylases by their common inhibitor, sodium tungstate, suppresses biochemical and oxidative stress markers of hepatic tissue damage. On the contrary, Mo-Fe-S flavin hydroxylases did not show any change in animals receiving AAP and BB. Correspondingly, sodium tungstate could not attenuate damage in AAP and BB treated groups of rats. The study concludes that Mo-Fe-S hydroxylases contribute to the hepatic injury inflicted by free radical generating agents and does not play any role in hepatic injury produced by glutathione depleting agents. The study has implication in understanding human liver diseases caused by a variety of agents, and to investigate the efficacy of the inhibitors of Mo-Fe-S flavin hydroxylases as potential therapeutic agents.

• Authors: Shakir Ali, Sonica Pawa, Mohammad Naime, Ram Prasad, Tasleem Ahmad, H Farooqui, Hina Zafar
• Journal: Life sciences (Life Sci) Vol. 82 Issue 13-14 Pg. 780-8 (Mar 26 2008) ISSN: 0024-3205 [Print] Netherlands
• PMID: 18313080 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Coenzymes
• Metalloproteins
• Molybdenum Cofactors
• Pteridines
• Flavin Mononucleotide
• molybdenum cofactor
• Xanthine Oxidase
• Aldehyde Oxidase

Topics

• Aldehyde Oxidase (metabolism)
• Animals
• Antioxidants (metabolism)
• Chemical and Drug Induced Liver Injury (enzymology, etiology, pathology)
• Coenzymes (metabolism)
• Cytosol (enzymology)
• Female
• Flavin Mononucleotide (metabolism)
• Liver (enzymology, pathology)
• Metalloproteins (metabolism)
• Molybdenum Cofactors
• Necrosis
• Oxidative Stress
• Pteridines (metabolism)
• Rats
• Rats, Wistar
• Xanthine Oxidase (metabolism)