title: Rosuvastatin ameliorates diabetes-induced reproductive damage via suppression of oxidative stress, inflammatory and apoptotic pathways in male rats.
abstract: OBJECTIVE
  Besides a cholesterol-lowering effect, rosuvastatin (RUV) possesses antioxidant and anti-inflammatory properties. The present study investigates the possible protective effects of RUV in diabetes-induced reproductive damage in rats.
  
  
  METHODS
  Diabetes was induced in male Wistar rats by injecting a single dose of streptozotocin (65mg/kg, i.p.). RUV in low and high doses (5 and 10mg/kg, p.o.) were administrated to diabetic rats for 8weeks. Reproductive damage was evaluated by estimation of testes and epididymis relative weights and caudal sperm count and motility in the control, untreated and RUV-treated diabetic rats. In addition, testicular malondialdehyde, reduced glutathione and nitric oxide levels, as well as, superoxide dismutase and myeloperoxidase activities were estimated. Finally, expressions of inflammatory [inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB)] and apoptotic (caspase-3) markers besides histological examination of testicular tissues were performed.
  
  
  RESULTS
  Results showed that RUV improved sperm count and motility with decrease in testicular nitric oxide and malondialdehyde levels, as well as, myeloperoxidase activity and increase in reduced glutathione level and superoxide dismutase activity in diabetic rats. Further, RUV reduced testicular inflammation and cell death by decreasing the expressions of iNOS, NF-κB and caspase-3.
  
  
  CONCLUSIONS
  Treatment with RUV protects against diabetes-induced testicular damage, in a dose dependent manner, through antioxidant, anti-inflammatory and anti-apoptotic mechanisms.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt.
authors.forename: Gehan Hussein
authors.initials: GH
authors.lastname: Heeba
authors.affiliation: Hormone Evaluation Department, National Organization for Drug Control and Research (NODCAR), Giza, Egypt. Electronic address: alaa17mm@gmail.com.
authors.forename: Alaaeldin Ahmed
authors.initials: AA
authors.lastname: Hamza
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004822:Epididymis / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D007248:Infertility, Male / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium / Q000494:pharmacology* / Q000627:therapeutic use*; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013737:Testis / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D009569:Nitric Oxide; D013739:Testosterone; D008315:Malondialdehyde; D000068718:Rosuvastatin Calcium
keywords: Apoptosis; Diabetic rat; Inflammation; Oxidative stress; Rosuvastatin; Testicular damage