title: Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice.
abstract: BACKGROUND
  Currently, the outcomes of the use of cisplatin in cancer therapy is limited by nephrotoxicity.
  
  
  OBJECTIVE
  This study aims to investigate the nephroprotective role of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice.
  
  
  METHODS
  Adult female Wistar Albino mice were divided into eight groups (n = 8). Group I served as normal control. Groups II, III and IV received apigenin (3 mg/kg, i.p.), myricetin (3 mg/kg, i.p.) or their combination respectively, for seven days. Group V served as positive control group, received vehicles for seven days and cisplatin (7.5 mg/kg, i.p.) for three days starting at day five. Groups VI, VII and VIII received apigenin, myricetin or their combination, respectively for seven days as well as cisplatin injection for three days starting at day five. by the end of the experimental period, a biochemical study involving, nephrotoxicity markers [serum creatinine (Cr) and blood urea nitrogen (BUN)], apoptotic marker [caspase 3], inflammatory mediators [tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase I and II (COXI, COXII)] and oxidative stress biomarkers [malondialdehyde (MDA), reduced glutathione (GSH) and catalase] was conducted. In addition, renal histopathological alterations were evaluated.
  
  
  RESULTS
  Apigenin, myricetin and their combination significantly reduced blood BUN, serum Cr, caspase-3TNF-α, IL-6, COXI and COXII, MDA levels and significantly increased GSH level and catalase activity parallel to, histopathological improvement in kidney tissues.
  
  
  CONCLUSIONS
  Apigenin and myricetin exhibited a protective and promising preventive strategy against cisplatin-induced nephrotoxicity due to their antioxidant and anti-inflammatory effects.
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Fayoum University , Fayoum , Egypt.
authors.forename: Samar M
authors.initials: SM
authors.lastname: Hassan
authors.affiliation: b Department of Pharmacology and Toxicology, Faculty of Pharmacy , Beni-Suef University , Beni-Suef , Egypt.
authors.forename: Marwa M
authors.initials: MM
authors.lastname: Khalaf
authors.affiliation: c Department of Pharmacology and Toxicology, Faculty of Medicine , Fayoum University , Fayoum, Egypt.
authors.forename: Sawsan A
authors.initials: SA
authors.lastname: Sadek
authors.affiliation: b Department of Pharmacology and Toxicology, Faculty of Pharmacy , Beni-Suef University , Beni-Suef , Egypt.
authors.forename: Amira M
authors.initials: AM
authors.lastname: Abo-Youssef
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D047310:Apigenin / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; C040015:myricetin; D047310:Apigenin; D053148:Caspase 3; D002945:Cisplatin
keywords: Antineoplastic; anti-inflammatory; antioxidant; inflammation; oxidative stress; prophylaxis