Protective Effects of Molsidomine Against Cisplatin-Induced Nephrotoxicity

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 (Adv Clin Exp Med 2015, 24, 4, 585-593).

The effect of anakinra to nephrotoxicity with cisplatin induced in rats: Biochemical, gene expression and histopathological evaluation

“…26 It has also been reported that the SOD activity decreases in the kidney tissue with tubular damage, apoptosis and inflammation due to cisplatin treatment. 27 These results support the hypothesis that cisplatin nephrotoxicity is associated with oxidative stress.…”

The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin induced nephrotoxicity: A rat model

“…These side effects lead to rapid weight loss secondary to malnutrition and dehydration in patients [26]. While there are some studies in the literature showing that there is no change in body weight in rats receiving cisplatin [27,28], other studies generally reported decrease in body weight [11,13,21,22]. Significant weight loss was observed in all groups in this study whether receiving or not receiving cisplatin.…”

“…As it is known that cisplatin nephrotoxicity also involves inflammation in addition to oxidative stress [16], it can be said that the assessment of activity and/or concentration of neutrophil-specific MPO would be important for the diagnosis and monitorization of nephrotoxicity. Moreover, it was demonstrated that MPO levels were significantly higher, or in other words, neutrophil activation was increased, in the animals receiving cisplatin compared to the healthy animals [27,34].…”

Supplementation of American ginseng berry extract mitigated cisplatin-evoked nephrotoxicity by suppressing ROS-mediated activation of MAPK and NF-κB signaling pathways

“…Cisplatin (cis-diamminedichloroplatinum), a typical platinum-based agent during "the war on cancer", is widely used to treat many types of cancers within the effective dose range, including cervical, ovarian, head, neck and non-small cell lung carcinoma. It is particularly effective in testicular cancer, with a cure rate of more than 90% (Karakoc et al, 2015;Miyagi et al, 2014) . .…”