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

Abstract

Cisplatin (CIS) is used in the treatment of cancer, but its nonspecific systemic actions lead to toxic effects on other parts of the body. This study investigated the severity of CIS toxicity by increasing its dose over a constant time period. Sprague Dawley rats were divided into five treatment groups and control group with CIS (2, 4, 6, 8, and 10 mg/kg) administered intraperitoneally for 5 days. The body and organs were weighed, epididymal sperm was counted, and sperm motility and sperm apoptosis were evaluated. Blood samples were evaluated for complete blood count, reactive oxygen and nitrogen species, malondialdehyde levels, and total testosterone. The testicular tissue was examined for steroidogenic acute regulatory protein and endoplasmic reticulum stress protein. Epididymal sperm was collected for CatSper Western blot. The toxic effects of different doses of CIS on the testis and kidney were compared histologically. The weights of body, testis, epididymis, prostate, seminal vesicle, and kidney; sperm count; sperm motility; steroidogenic acute regulatory protein level; and epididymal sperm count were significantly lower in the CIS-treated groups than in the control group. In contrast, sperm apoptosis, plasma reactive oxygen and nitrogen species, and malondialdehyde, testosterone, red blood cell, hematocrit, hemoglobin, and endoplasmic reticulum stress protein levels all increased. Though CIS effectively treats cancer, at an increased dose it is toxic and life-threatening to the genitourinary system and other parts of the body.

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

“…caspase-12, a marker of apoptosis, is localized on the ER and is specifically activated via erS, and not via membrane or mitochondrial signals. it has been reported that erS-mediated apoptosis is important in cP-induced nephrotoxicity, suggesting that er is a target of cP, and that GrP78, caspase-12 and cHoP are important molecules (9,40,41).…”

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

“…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.…”

Ginger juice prevents cisplatin‐induced oxidative stress, endocrine imbalance and NO/iNOS/NF‐κB signalling via modulating testicular redox‐inflammatory mechanism in rats

“…Leydig cells that produce testosterone are suggested to be susceptible to ROS damage (Soni et al, 2016) (Fathabad, Shekarforoush, Hoseini, & Ebrahimi, 2018;Morakinyo, Achema, & Adegoke, 2010). It is thus conceivable that the restoration of the sex hormones could be mediated by the action of ginger juice compounds on Leydig cells and hypothalamic-pituitary axis.…”