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Cyclophosphamide-induced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum (Asteraceae) in male Wistar rats
Institution:1. Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India;2. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India;3. Department of Biosciences, Jamia Millia Islamia,110025 New Delhi, India;1. Past Director of Nephrology Division in Ospedale Maggiore, Milano, Italy;2. Nephrology Unit, Centro Hospitalar do Médio Tejo, Avenida Xanana Gusmao, Ap. 45, 2350-754 Torres Novas, Portugal;3. Nephrology Unit, Fondazione Ca’ Granda IRCCS Ospdale Maggiore Policlinico Milano, Via della Commenda 15. 20122 Milano, Italy
Abstract:ObjectiveCyclophosphamide (CP) is commonly used to treat some cancers, but its clinical efficacy is also linked with testicular toxicity. We investigated the effects of aqueous extract (AE) and methanolic extract (ME) of Helichrysum odoratissimum for reducing CP-induced reproductive toxicity in male rats.MethodsIn addition to a normal control (group 1), drugs or vehicles were administered orally to seven groups (n = 5) of rats that had already received 4-weeks of pre-treatment with CP (5 mg/kg·d], per oral administration); group 2 received CP + distilled water (10 mL/kg·d]); group 3 received CP + 5% tween 80 (10 mL/kg·d]); group 4 received CP + clomiphene citrate (0.25 mg/kg·d]); groups 5 and 6 received CP + AE (50 and 100 mg/kg·d]) and groups 7 and 8 received CP + ME (50 and 100 mg/kg·d]). Animals were sacrificed on day 15, and body and sexual organ weights, sperm characteristics, testosterone level and testicular histology were evaluated.ResultsThe CP-treated group showed a significant reduction (P < 0.001) in the body and seminal vesicle weights, testosterone level, sperm count, sperm motility and sperm viability, but elevated (P < 0.001) sperm morphological abnormalities and testicular structure alterations, compared to the control group. Interestingly, these detrimental effects of CP were reversed by treatment with H. odoratissimum extracts. For instance, both extracts and all doses of H. odoratissimum significantly increased the sperm count (P < 0.001), sperm motility (AE, 50 mg/kg, P < 0.05; ME, 50 and 100 mg/kg, P < 0.05) and sperm viability (AE, 50 mg/kg, P < 0.001; ME, 50 and 100 mg/kg, P < 0.001) compared to the CP group. H. odoratissimum also improved plasmatic and intratesticular testosterone levels and prevented histological alterations of the testes.ConclusionH. odoratissimum might be considered as an alternative drug to alleviate/prevent reproductive damage in cancer patients receiving CP chemotherapy.
Keywords:Cyclophosphamide  Reproductive toxicity  Rat
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