Carnosine Remedial Effect on Fertility of Male Rats Receiving Cyclophosphamide, Hydroxydaunomycin, Oncovin and Prednisone (CHOP)

Abstract

Chemotherapeutic agents can impair gonadal function triggering infertility. Here, we probed the properties of carnosine as an antioxidant in reproductive disorders caused by the combination of cyclophosphamide, hydroxydaunomycin (doxorubicin), oncovin (vincristine) and prednisone (CHOP); this combination is mostly used in treating non‐Hodgkin lymphoma. Animals were distributed into four groups: Group I was the control. Group II received carnosine (250mg kg day‐1, i.p.); Group III received CHOP: cyclophosphamide (27 mg/kg/cycle), doxorubicin (1.8 mg/kg/cycle) and vincristine (0.05 mg/kg /cycle) by i.p. plus oral prednisone (1.47 mg kg‐1 day‐1/cycle) for five days. Group IV received carnosine plus CHOP. The study involved 4 cycles each of 3 weeks. Also, we explored the effect of combining carnosine with CHOP on the development of solid Ehrlich carcinoma in mice. CHOP lowered genitals weight, sperm count and motility, testicular function marker enzymes, serum testosterone level and gene expression of 3β‐hydroxysteroid dehydrogenase, 17β‐hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein. Furthermore, CHOP elevated testicular oxidative stress, serum follicle‐stimulating hormone, luteinising hormone and triggered DNA damage. Morphometric and histopathological examinations of testicular tissues buttressed the biochemical results. Importantly, administration of carnosine ameliorated CHOP‐induced alterations without diminishing CHOP's antineoplastic action. These results indicated that carnosine may ameliorate reproductive disorders induced by CHOP.

Alkylating agents‐induced gonadotoxicity in prepubertal males: Insights on the clinical and preclinical front

“…So far, most studies have been conducted in adult murines. As expected, given that most regimens employ the use of alkylating with non-alkylating drugs, most research is concentrated on regimens like the BEP protocol (bleomycin, etoposide, and cisplatin), [152][153][154] a standard treatment for testicular cancer, and the CHOP protocol (cyclophosphamide, doxorubicin, vincristine, and prednisolone), 155,156 common in the treatment for non-Hodgkin lymphoma. In prepubertal models, treatment with the BEP combination had no synergistic effect on spermatogonia cluster formation in culture.…”