The effects of MOTILIPERM on cisplatin induced testicular toxicity in Sprague–Dawley rats

Abstract

Background Cisplatin causes male infertility but the exact mechanism have not been clarified, yet. MOTILIPERM has been implicated in alleviation of infertility in Sprague–Dawley rats caused by cisplatin. We evaluated recovery effect of MOTILIPERM on cisplatin (CIS)-induced testicular toxicity in Sprague–Dawley rats.Methods Five groups were included. The groups are control (CTR), CTR + MOTILIPERM 200 mg/kg/day per oral, CIS 10 mg/kg i.v., CIS 10 mg/kg + MOTILIPERM 100 mg/kg/day, CIS 10 mg/kg + MOTILIPERM 200 mg/kg/day. CIS 10 mg/kg i.v. single dose was given before 100 mg/kg, or 200 mg/kg MOTILIPERM per oral daily for 28 days. Body and genital organs weight, epididymis sperm count, sperm motility, sperm apoptosis, testosterone level, MDA of testis tissue, spermatogenic cell density, and Johnsen’s score were evaluated. Steroidogenic acute regulatory (StAR) protein, and Glucose-regulated protein-78 (GRP-78), phosphorylated Inositol-Requiring Transmembrane Kinase/Endoribonuclease 1 (IRE1) and phosphorylated c-jun-N-terminal kinase (p-JNK) were quantitated by western blot to show its signaling pathway.ResultsThe body weight was decreased significantly in CIS 10 mg/kg, CIS 10 mg/kg + MOTILIPERM 100 mg/kg/day, CIS 10 mg/kg + MOTILIPERM 200 mg/kg/day compared with CTR (p < 0.001) however, it was increased in CIS 10 mg/kg + MOTILIPERM 100 mg/kg/day, CIS 10 mg/kg + MOTILIPERM 200 mg/kg/day compared with CIS 10 mg/kg. The decreased weight of epididymis and prostate were increased significantly in CIS 10 mg/kg + MOTILIPERM 100 mg/kg/day compared with CIS 10 mg/kg. Sperm count, sperm motility, sperm apoptosis, MDA of testis tissue, spermatogenic cell density, Johnsen’s score, and total testosterone were also significantly improved by MOTILIPERM treatment. The levels of decreased StAR protein was significantly improved by MOTILIPERM administration, increased GRP-78 protein p-IRE1and p-JNK was also significantly decreased with MOTILIPREM treatment.ConclusionThe MOTILIPERM could be an effective medicine to reduce the toxic effect caused ER stress by CIS in the testis.

Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress

“…Furthermore, the StAR protein level, which was first identified in mid-1980s, has been shown to be important for transferring cholesterol,11,21 from the outer to the inner mitochondrial membrane to synthesize testosterone 22. StAR protein was significantly lower in the CIS-treated groups than in the control group, thus interfering with testosterone production.…”

“…Then, the sections were examined under a light microscope to obtain spermatogenic cell density measurements and renal injury scores. Spermatogenic cell density was determined by measuring the thickness of the germinal cell layer and the diameter of the seminiferous tubules 11. The amount of kidney tubular damage was scored according to the percentage of cortical tubules with epithelial necrosis: 0, normal; 1, ≤10%, 2, 10%–25%, 3, 26%–75%, and 4, ≥75%.…”

Protective effect of melatonin versus montelukast in cisplatin-induced seminiferous tubule damage in rats

“…The discrepancy with our results may be linked to the rat strain used, as the Wistar rats in this study had severe reduction in sperm count (to 12% of control). Other studies using Wistar rats have documented >50% reduction in sperm count induced by cisplatin (Hamza, Elwy, & Badawi, ; Heeba, Hamza, & Hassanin, ), while studies using Sprague Dawley rats often report no effect or a relatively modest effect of cisplatin on sperm count (Aksu et al., ; Soni et al., ). Collectively, our findings together with previous studies suggest that Wistar rats may be more suitable than Sprague Dawley rats for modelling the reduction in sperm count induced by cisplatin.…”

“…In this study, a single dose of cisplatin induced a substantial weight loss of 8% of body weight by day 5, and 16% by day 10 (compared to 10% weight gain in controls at day 10). This general toxicity of cisplatin in rats is recognised (Ilbey, Ozbek, Cekmen, et al., ; Ilbey, Ozbek, Simsek, et al., ; Soni et al., ), and has been shown to be linearly dependent on cisplatin dose (Soni et al., ). Weight loss, largely due to anorexia, affects 50%–90% of patients receiving cisplatin (Hesketh, ), and is a debilitating problem for patients who are unable to maintain adequate nutrition, contributing to reduced quality of life.…”

Protective effects of melatonin on testis histology following acute torsion-detorsion in rats

“…Several studies in the past indicated that torsion can injure testis and its germ cells (23-25). The spermatic cord torsion is an emergency event that is needed an invasive surgery procedure.…”