title: Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats.
abstract: BACKGROUND
  An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD) were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of this work was to examine possible gender-related differences and the possible protective effects of rutin and ascorbic acid supplementation on high cholesterol diet induced nephrotoxicity.
  
  
  METHODS
  96 young male and female Wistar albino rats were used. HCD supplemented animals were treated with rutin alone or in combination with ascorbic acid for 6 weeks. Creatinine plasma level was estimated. Furthermore, kidney levels of nucleic acids, total protein, malondialdehyde (MDA), reduced glutathione (GSH), total cholesterol, and triglycerides were determined. Finally, kidney tissues were used for histopathological examination.
  
  
  RESULTS
  HCD supplementation decreased kidney level of nucleic acids, which was more prominent in female animals. Both vitamin combination significantly attenuated HCD induced decrease in nucleic acids. Moreover, kidney level of MDA was significantly altered by HCD in both genders, which was inhibited by rutin and ascorbic acid alone or in combination in male groups and by both vitamins in female groups. There was a reduction in kidney level of GSH by HCD, especially in male groups, which was attenuated by rutin and ascorbic acid combination. Kidney levels of total cholesterol and triglycerides were significantly increased by HCD supplementation in both genders. Coadministration with rutin and/or ascorbic acid protected from such increase, which was more obvious in both vitamins combination. Histopathological investigation supported vitamins protective effect, which was more prominent in male vitamins combination group.
  
  
  CONCLUSIONS
  HCD-induced renal injury in female was higher than in male animals, suggesting a better anti-oxidative stress defense response in male's kidney. Moreover, the antioxidant and reno-protective effects of rutin and ascorbic acid were augmented following their combination.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, P.O. Box 2457, King Saud University, Riyadh 11451, Saudi Arabia. rejaie@hotmail.com
authors.forename: Salim Salih
authors.initials: SS
authors.lastname: Al-Rejaie
authors.forename: Hatem Mustafa
authors.initials: HM
authors.lastname: Abuohashish
authors.forename: Osama Abdelrahman
authors.initials: OA
authors.lastname: Alkhamees
authors.forename: Abdulaziz Mohammed
authors.initials: AM
authors.lastname: Aleisa
authors.forename: Abdulaziz S
authors.initials: AS
authors.lastname: Alroujayee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D002784:Cholesterol / Q000009:adverse effects / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000209:etiology; D012431:Rutin / Q000494:pharmacology / Q000627:therapeutic use*; D012737:Sex Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D009696:Nucleic Acids; D011506:Proteins; D014280:Triglycerides; D008315:Malondialdehyde; D012431:Rutin; D002784:Cholesterol; D003404:Creatinine; D005978:Glutathione; D001205:Ascorbic Acid