title: Role of the KATP channel in the protective effect of nicorandil on cyclophosphamide-induced lung and testicular toxicity in rats.
abstract: This study is the first to investigate the role of the KATP channel in the possible protection mediated by nicorandil against cyclophosphamide-induced lung and testicular toxicity in rats. Animals received cyclophosphamide (150 mg/kg/day, i.p.) for 2 consecutive days and then were untreated for the following 5 days. Nicorandil (3 mg/kg/day, p.o.) was administered starting from the day of cyclophosphamide injection with or without glibenclamide (5 mg/kg/day, p.o.). Nicorandil administration significantly reduced the cyclophosphamide-induced deterioration of testicular function, as demonstrated by increases in the level of serum testosterone and the activities of the testicular 3β- hydroxysteroid, 17β-hydroxysteroid and sorbitol dehydrogenases. Furthermore, nicorandil significantly alleviated oxidative stress (as determined by lipid peroxides and reduced glutathione levels and total antioxidant capacity), as well as inflammatory markers (tumour necrosis factor-α and interleukin-1β), in bronchoalveolar lavage fluid and testicular tissue. Finally, the therapy decreased the levels of fibrogenic markers (transforming growth factor-β and hydroxyproline) and ameliorated the histological alterations (as assessed by lung fibrosis grading and testicular Johnsen scores). The co-administration of glibenclamide (a KATP channel blocker) blocked the protective effects of nicorandil. In conclusion, KATP channel activation plays an important role in the protective effect of nicorandil against cyclophosphamide-induced lung and testicular toxicity.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Lamiaa A
authors.initials: LA
authors.lastname: Ahmed
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Shohda A
authors.initials: SA
authors.lastname: El-Maraghy
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Sherine M
authors.initials: SM
authors.lastname: Rizk
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001835:Body Weight; D003520:Cyclophosphamide / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D054086:KATP Channels; D017997:Leukotriene C4 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020108:Nicorandil / Q000494:pharmacology*; D009929:Organ Size; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D013737:Testis / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D054086:KATP Channels; D020011:Protective Agents; D020108:Nicorandil; D017997:Leukotriene C4; D013739:Testosterone; D006632:Histamine; D003520:Cyclophosphamide; D000118:Acetylglucosaminidase; D005905:Glyburide