Maternal supplementation of alpha-lipoic acid ameliorates prenatal cytarabine-induced mutilation in reproductive development and function in F1 male adult rats.

AIMS: Cytarabine (CYT), a prevalent anticancer drug for blood cancers, detrimentally affects male reproductive development and function. Alpha-lipoic acid (ALA), a universal antioxidant, offers defense against chemical-induced reproductive dysfunction. Our study sought to explore ALA's protective role against prenatal CYT-induced reproductive impairment in F1 male adult rats. MAIN METHODS: Pregnant rats were divided into 5 groups and administered normal saline, ALA 200 mg/kg, CYT 12.5 mg/kg, CYT 25 mg/kg, and CYT 25 mg/kg + ALA 200 mg/ kg from gestational day 8 to 21. On postnatal day 73, F1 male rats were sacrificed, and general, oxidative, steroidogenic, spermatogenic, histological, and morphometrical parameters were evaluated. KEY FINDINGS: Prenatal CYT caused dose-dependent reductions in body weight, testis, and accessory gland weights; elevated oxidative stress; delayed puberty onset; sperm anomalies (decreased count, motility, viability, seminal fructose; increased morphological anomalies); impeded steroidogenesis (lower testosterone, follicle-stimulating hormone, luteinizing hormone, 3ß-Hydroxysteroid dehydrogenase(HSD), 17ß-HSD, and elevated cholesterol); and testicular histopathological and morphometric disturbances. Maternal supplementation of ALA was found to alleviate all the CYT-induced reproductive disruptions. SIGNIFICANCE: The present work accentuates the beneficial actions of ALA against CYT-induced impairment in reproductive development and functions by combating disruptions in oxidative balance, steroidogenesis, spermatogenesis, and testicular histological aberrations. However, future experimental and clinical studies are warranted to explore the molecular mechanisms involved in the ALA's protection against prenatal CYT-induced testicular injury.

Alpha-lipoic acid ameliorates cytarabine-induced developmental anomalies in rat fetus.

Cytarabine (Ara-C) is a nucleoside analogue used in the treatment of cancers and viral infections. It has teratogenic potential and causes a variety of birth defects in fetuses. Alpha-lipoic acid (ALA) is a natural antioxidant offers protection against the developmental toxicity induced by drug- or toxicant-exposure or pathological conditions. This study was aimed at evaluating the protective effect of ALA against Ara-C induced developmental toxicity in rat fetus. Pregnant rats divided into five groups and received normal saline, ALA200 mg/kg, Ara-C12.5 mg/kg, Ara-C25 mg/kg and, Ara-C25 mg/kg plus ALA200 mg/kg respectively from gestational day (GD) 8 to GD14 and sacrificed on GD21. Ara-C treatment led to a significant and dose-dependent decrease in food intake, weight gain, placental weight, and an increase in oxidative stress in pregnant rats. Further, the in-utero exposure to Ara-C led to an increase in fetal mortality, resorptions, oxidative stress, external morphological anomalies and limb abnormalities, and impaired ossification. Co-administration of ALA resulted in amelioration of the footprints of Ara-C induced toxicity in pregnant rats as well as the fetus. These findings indicate that the ALA supplementation offers protection against developmental toxicity caused by Ara-C prenatal exposure in rats.

Pre-pubertal cyclophosphamide exposure-induced mutilation in spermatogenesis, steroidogenesis and testicular architecture in SD rat: Protection from an alternative herbal viagra.

INTRODUCTION: The children and adolescents with cancer who are getting remission and becoming long-term survivals are at high risk of impaired fertility. Cyclophosphamide (CP), the most frequently used drug for childhood-cancers causes various types of reproductive toxicity. We aimed at evaluating protective role of chlorophytum borivillianum (CB) extract against pre-pubertal CP exposure-induced testicular toxicity in rats. MATERIALS AND METHODS: Sixty male pre-pubertal SD rats aged postnatal day (PND) 24 were divided into 5 groups. Group-I (control), group-II (CP), and group-III (CB) received normal saline (NS), CP15mg/kg/day and CB200mg/kg/day respectively during PND29-42; group-IV and group-V received CB100mg/kg/day and CB200mg/kg/day respectively along with CP15mg/kg/day for the same period. Half of the rats from each group were sacrificed on PND43 (puberty) to evaluate alterations in oxidative stress parameters and histopathology. Remaining rats were sacrificed on PND63 (young adult age) and sperm analysis (density, motility, viability, and morphology), hormonal (Testosterone, Luteinizing hormone, Follicle stimulating hormone) estimation and histomorphometrical evaluation was done. Co-administration of CB have shown a dose-dependent and significant improvement in anomalies caused by CP as compared to rats received CP only. RESULTS: CP treatment led to significant decrease in body weight gain, organ weights, oxidative defense mechanisms, hormone levels, steroidogenesis, spermatogenesis, sperm parameters and increase in oxidative stress, percentage of sperm abnormal morphology as compared to control rats. CP-treated rats have shown severe damage in testicular architecture and development as compared to control rats as evidenced by histopathology and morphometric analysis. CONCLUSION: Co-administration of CB extract significantly reversed the footprints of these effects in dose-dependent manner. These protective effects of CB may be exploited in improving gonadal function in childhood cancer long-term survivals.