Ameliorative effect of nerolidol on cyclophosphamide‐induced gonadal toxicity in Swiss Albino mice: Biochemical‐, histological‐ and immunohistochemical‐based evidences

Abstract

Cyclophosphamide (CP) is commonly used as antineoplastic and immunosuppressant drug with noticeable gonadotoxic profile. Nerolidol (NER) is a sesquiterpene with potent antioxidant and anti‐inflammatory properties. Thus, the present study was designed to explore its possible gonadal protective potential against cyclophosphamide‐induced testicular, epididymal, seminal and spermatozoal toxicities. Animals were divided into five groups: control (normal saline for 14 days), treatment group (NER 200 and 400 mg/kg, p.o) for 14 days along with a single dose of cyclophosphamide (200 mg/kg, i.p) on 7th day, toxic and Per se groups (cyclophosphamide 200 mg/kg i.p) on 7th day and NER 400 mg/kg for 14 days respectively. Animals were sacrificed on the 15 day, and body weight, weight of reproductive organs, testosterone level, sperm count, biochemical parameters, histopathological and immunohistochemical studies were performed in the testes, epididymis and in the serum. CP administration induced oxidative stress, nitrative stress, inflammation, reduced testosterone level, sperm count, increased expression of MPO and caused histological aberrations in the testes, epididymis and seminal vesicles. CP caused reduced sperm count, sperm motility and testosterone level which got reversed upon treatment with nerolidol in a dose‐dependent manner. Nerolidol thus acted as a gonadoprotective molecule and prevented the gonadotoxicity of CP.

Phycobiliproteins Ameliorate Gonadal Toxicity in Male Mice Treated with Cyclophosphamide

“…Our results are in agreement with the CP effects previously reported by Elangovan et al [ 25 ], Lu et al [ 7 ], and Iqubal et al [ 37 ] including reductions in serum testosterone, body weight, relative testis weight, and sperm parameter alterations; increases in lipoperoxidation and enzyme activity (SOD and GPX); and testicle damage observed by histology. The PBP crude extract mitigated certain CP effects, depending on the PBP dose administered.…”

Unravelling the Protective Effects of Emodin Against Cyclophosphamide Induced Gonadotoxicity in Male Wistar Rats

“…The undesirable consequences of CP on the reproductive system have been extensively highlighted in many reports. 12 , 13 , 37 The underlying factor associated with CP toxicity is mainly its ability to generate ROS and oxidative stress which subsequently impairs endocrine and gonadotropin secretion resulting in reduction of sex hormones, altered semen quality and decreased male fertility. In addition, CP-induced ROS perturbs spermatogenesis via the testicular-endocrine axis which alters the production of follicle stimulating hormone, luteinizing hormone causing subnormal levels of testosterone.…”

“… 11 CP induced testicular toxicity is associated with impaired spermatogenesis, reduced sperm functionality, reproductive hormone and testicular weight. 12 , 13 Several studies have suggested that acrolein, an enzymatic toxic metabolite of CP promotes the generation of reactive oxygen species and lipid peroxidation, thus inducing oxidative stress and oxidative damage. 12 Furthermore, the abundance of polyunsaturated fatty acids as well as the low levels of antioxidants in the testes and spermatozoa exposes the tissues to oxidative stress and damages.…”

“… 12 Furthermore, the abundance of polyunsaturated fatty acids as well as the low levels of antioxidants in the testes and spermatozoa exposes the tissues to oxidative stress and damages. 12 , 13 Unfortunately, despite the widely reported testicular toxicity associated with CP, there is no approved agent till date to counteract CP-induced gonadotoxicity.…”

Mechanisms Involved in Microglial-Interceded Alzheimer’s Disease and Nanocarrier-Based Treatment Approaches

“…Oxidative stress is the result of excess reactive oxygen species (ROS) production. ROS are produced in normal physiological conditions, such as during cellular metabolism in the mitochondria, and in the diseased state excess ROS are produced [12]. Either dysfunctional mitochondria or the reduced activity of endogenous antioxidants, such as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), is accountable for the production of ROS [12].…”