title: Hesperidin alleviates cisplatin-induced hepatotoxicity in rats without inhibiting its antitumor activity.
abstract: BACKGROUND
  Hesperidin, a naturally occurring flavonoid, exerts many clinically appreciable effects such as anti-oxidant, anti-allergic and anti-inflammatory actions. The present study aimed to investigate the possible protective effects of multiple doses of hesperidin against cisplatin-induced acute hepatotoxicity in rats.
  
  
  METHODS
  Hesperidin (100 or 200mg/kg po) was given to rats one day before cisplatin (7.5mg/kg, ip) injection. All animals were sacrificed 5 days after cisplatin injection and blood samples were collected for determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, triglycerides (TG) and total cholesterol levels. Liver samples were used for the determination of malondialdehyde (MDA), glutathione (GSH), total nitrate and nitrite contents. Western blot analysis was used for the assessment of NF-κB and p-Akt expression and histopathological examination was also performed.
  
  
  RESULTS
  Results showed that hesperidin significantly reduced cisplatin-induced elevations in serum ALT and AST activities, TG and total cholesterol levels. It also reduced cisplatin-induced oxidative stress by significant reduction in liver MDA and NO content and elevation of GSH content. In addition, hesperidin significantly counteracted cisplatin-induced increased NF-κB expression and decreased p-Akt expression. Histopathological examination revealed that hesperidin greatly protected liver against cisplatin-induced injury. Moreover hesperidin did not inhibit the cytotoxic effect of cisplatin on cancer cells as determined by MTT assay.
  
  
  CONCLUSIONS
  Hesperidin decreased cisplatin-induced functional and histopathological liver damage in a dose-dependent manner without affecting its potential cytotoxic effect.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; Sharjah Institute for Medical Research, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates.
authors.forename: Hany A
authors.initials: HA
authors.lastname: Omar
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Wafaa R
authors.initials: WR
authors.lastname: Mohamed
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Electronic address: elshimaa.arafa@pharm.bsu.edu.eg.
authors.forename: El-Shaimaa A
authors.initials: el-SA
authors.lastname: Arafa
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Basim A
authors.initials: BA
authors.lastname: Shehata
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafr El-Sheikh University, Kafr El-Sheikh, Egypt.
authors.forename: Gamal A
authors.initials: GA
authors.lastname: El Sherbiny
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Hany H
authors.initials: HH
authors.lastname: Arab
authors.affiliation: Department of Pharmacology, Faculty of Veterinary medicine, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Abdel Nasser A M
authors.initials: AN
authors.lastname: Elgendy
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D014280:Triglycerides; D008315:Malondialdehyde; D002784:Cholesterol; D006569:Hesperidin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D051057:Proto-Oncogene Proteins c-akt; D005978:Glutathione; D002945:Cisplatin
keywords: Cisplatin; Hepatotoxicity; Hesperidin; Oxidative stress; Western blot