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Pre-pubertal cyclophosphamide exposure-induced mutilation in spermatogenesis, steroidogenesis and testicular
Ramanachary Namoju1, Naga Kavitha Chilaka2, Durga Prasad Beda3
1Department of Pharmacology, GITAM Institute of Pharmacy, GITAM Deemed to be University, Vishakhapatnam, Andhra Pradesh 530045, India; Bhaskar Pharmacy College, Jawaharlal Nehru Technical University, Hyderabad, Telangana 500075, India.
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.
