title: Alleviation of hepatic injury by chrysin in cisplatin administered rats: probable role of oxidative and inflammatory markers.
abstract: BACKGROUND
  Cisplatin is an effective and extensively used chemotherapeutic agent to treat range of malignancies, but its therapeutic use is limited because of dose-dependent nephrotoxicity and hepatotoxicity. Several published reports advocate that supplementation with antioxidant can influence cisplatin induced hepatic damage.
  
  
  METHODS
  In the present study the Wistar rats were subjected to concurrent prophylactic oral treatment of chrysin (25 and 50mg/kgb.wt.) against the hepatotoxicity induced by intraperitoneal administration of cisplatin (7.5mg/kgb.wt.). Efficacy of chrysin against the hepatotoxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, histopathological changes and expression levels of molecular markers of inflammation.
  
  
  RESULTS
  Chrysin ameliorated cisplatin-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, superoxide dismutase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated expression of COX-2, iNOS and levels of NFκB and TNF-α, and hepatic tissue damage which were induced by cisplatin. Histological findings further supported the protective effects of chrysin against cisplatin-induced hepatic damage.
  
  
  CONCLUSIONS
  The results of the present study demonstrate that oxidative stress and inflammation are closely associated with cisplatin-induced toxicity and chrysin shows the protective efficacy against cisplatin-induced hepatotoxicity possibly via attenuating the oxidative stress and inflammatory response.
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Muneeb U
authors.initials: MU
authors.lastname: Rehman
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Nemat
authors.initials: N
authors.lastname: Ali
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Summya
authors.initials: S
authors.lastname: Rashid
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Tyan
authors.initials: T
authors.lastname: Jain
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Sana
authors.initials: S
authors.lastname: Nafees
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Mir
authors.initials: M
authors.lastname: Tahir
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Abdul Quaiyoom
authors.initials: AQ
authors.lastname: Khan
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Abdul
authors.initials: A
authors.lastname: Lateef
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Rehan
authors.initials: R
authors.lastname: Khan
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Oday O
authors.initials: OO
authors.lastname: Hamiza
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Syed
authors.initials: S
authors.lastname: Kazim
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Wajhul
authors.initials: W
authors.lastname: Qamar
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India. Electronic address: Sarwat786@rediffmail.com.
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control*; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D015415:Biomarkers; D005419:Flavonoids; C043561:chrysin; D002945:Cisplatin
keywords: Cisplatin; Hepatotoxicity; Inflammation; Oxidative stress