title: Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats.
abstract: Fisetin, a known antioxidant, has been found to be cytotoxic against certain cell lines. However, the mechanism by which it inhibits tumor growth in vivo remains unexplored. Recently, we have demonstrated that Aflatoxin-B1 (AFB1) induced hepatocarcinogenesis is associated with activation of oxidative stress-inflammatory pathway in rat liver. The present paper describes the effect of in vivo treatment with 20 mg/kg b.w. Fisetin on antioxidant enzymes vis-a-vis oxidative stress level and on the profile of certain proinflammatory cytokines in the hepatocellular carcinoma (HCC) induced by two doses of 1 mg/kg b.w. AFB1 i.p. in rats. The reduced levels of most of the antioxidant enzymes, coinciding with the enhanced level of reactive oxygen species in the HCC liver, were observed to regain their normal profiles due to Fisetin treatment. Also, Fisetin treatment could normalize the enhanced expression of TNFα and IL1α, the two proinflammatory cytokines, reported to be involved in HCC pathogenesis. These observations were consistent with the regression of neoplastic lesion and declined GST-pi (placental type glutathione-S-transferase) level, a HCC marker, in the liver of the Fisetin treated HCC rats. The findings suggest that Fisetin attenuates oxidative stress-inflammatory pathway of AFB1 induced hepatocarcinogenesis.
authors.affiliation: Biochemistry Section, Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Brajesh Kumar
authors.initials: BK
authors.lastname: Maurya
authors.affiliation: Biochemistry Section, Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Surendra Kumar
authors.initials: SK
authors.lastname: Trigun
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D053582:Interleukin-1alpha / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000096:biosynthesis*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D044948:Flavonols; D053582:Interleukin-1alpha; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D016604:Aflatoxin B1; D010088:Oxidoreductases; C017875:fisetin