Habib T E Karakoc1, Ramazan Altintas2, Hakan Parlakpinar3, Alaaddin Polat4, Emine Samdanci5, Mustafa Sagir3, Zeynep R Duran4. 1. Student, Medical Faculty, Inonu University, Malatya, Turkey. 2. Department of Urology, Medical Faculty, Inonu University, Malatya, Turkey. 3. Department of Physiology, Medical Faculty, Inonu University, Malatya, Turkey. 4. Department of Pharmacology, Medical Faculty, Inonu University, Malatya, Turkey. 5. Department of Pathology, Medical Faculty, Inonu University, Malatya, Turkey.
Abstract
BACKGROUND: Cisplatin, an effective chemotherapeutic agent, is used for the treatment of several types of cancers. However, cisplatin has some severe side effects such as nephrotoxicity. On the other hand, molsidomine, a NO donor, has anti-oxidative and vasodilator effects. OBJECTIVES: The aim of this study was to estimate the protective effects of molsidomine on cisplatin-induced nephrotoxicity. MATERIAL AND METHODS: Thirty-two rats were randomly divided into 4 groups as follows: (1) control; (2) received a single-dose intraperitoneal (i.p.) injection of 5 mg/kg cisplatin; (3) received single i.p. dose of molsidomine (4 mg/kg/day) for 3 consecutive days before cisplatin treatment; (4) received single i.p. dose of molsidomine (4 mg/kg/day) for 3 consecutive days. The specific biochemical markers, including antioxidants, and the histopathological alterations were evaluated. RESULTS: Cisplatin significantly increased malondialdehyde (MDA) and myeloperoxidase (MPO) levels and decreased glutathione peroxidase (GPX) level. Molsidomine significantly decreased MPO level nearly to control level; however, its ameliorating effects on MDA, SOD, CAT and GPX did not reach to significant levels. Cisplatin-induced elevation of blood-urea-nitrogen and serum-creatinine were diminished after molsidomine administration. Cisplatin also induced severe tubular degeneration, nuclear condensation, apoptosis and scattered patchy inflammation in the histological examination. Molsidomine improved all of these histological damages. CONCLUSIONS: In this study, the beneficial effect of molsidomine against cisplatin nephrotoxicity has been evaluated for the first time.
BACKGROUND:Cisplatin, an effective chemotherapeutic agent, is used for the treatment of several types of cancers. However, cisplatin has some severe side effects such as nephrotoxicity. On the other hand, molsidomine, a NO donor, has anti-oxidative and vasodilator effects. OBJECTIVES: The aim of this study was to estimate the protective effects of molsidomine on cisplatin-induced nephrotoxicity. MATERIAL AND METHODS: Thirty-two rats were randomly divided into 4 groups as follows: (1) control; (2) received a single-dose intraperitoneal (i.p.) injection of 5 mg/kg cisplatin; (3) received single i.p. dose of molsidomine (4 mg/kg/day) for 3 consecutive days before cisplatin treatment; (4) received single i.p. dose of molsidomine (4 mg/kg/day) for 3 consecutive days. The specific biochemical markers, including antioxidants, and the histopathological alterations were evaluated. RESULTS:Cisplatin significantly increased malondialdehyde (MDA) and myeloperoxidase (MPO) levels and decreased glutathione peroxidase (GPX) level. Molsidomine significantly decreased MPO level nearly to control level; however, its ameliorating effects on MDA, SOD, CAT and GPX did not reach to significant levels. Cisplatin-induced elevation of blood-urea-nitrogen and serum-creatinine were diminished after molsidomine administration. Cisplatin also induced severe tubular degeneration, nuclear condensation, apoptosis and scattered patchy inflammation in the histological examination. Molsidomine improved all of these histological damages. CONCLUSIONS: In this study, the beneficial effect of molsidomine against cisplatinnephrotoxicity has been evaluated for the first time.
Authors: Alfredo G Casanova; María Teresa Hernández-Sánchez; Francisco J López-Hernández; Carlos Martínez-Salgado; Marta Prieto; Laura Vicente-Vicente; Ana Isabel Morales Journal: Eur J Clin Pharmacol Date: 2019-11-01 Impact factor: 2.953