Carnitine reduces testicular damage in rats treated with etoposide in the prepubertal phase

Abstract

Etoposide is a chemotherapeutic agent that induces cell death by blocking topoisomerase II catalytic function. Although etoposide is effective in the treatment of cancer, it also causes the death of normal proliferating cells, including male germ cells. Administration of etoposide during the prepubertal phase causes diturbances in several testicular morphometric parameters and in Sertoli cells. Cytoprotection of the seminiferous epithelium is the only means of preserving potential male reproduction in prepubertal cancer patients. Carnitine, an amino acid naturally present in normal cells, is a promising cryoprotectant as it is concentrated in the epididymis and promotes sperm maturation. We have therefore investigated whether carnitine protects rat testes against etoposide and, thus, improves fertility in adulthood. Our results suggest that carnitine partially protects the testis against damage caused by etoposide, although the mechanism by which it happens remains unknown.

Carnitine partially protects the rat testis against the late damage produced by doxorubicin administered during pre‐puberty

“…Thus, the present results corroborate the antiapoptotic role of carnitine and reinforce the improved outcomes of quantitative and qualitative sperm parameters noticed in the carnitine+doxorubicin-treated rats. Similar results were obtained by our group when carnitine was previously administered to etoposide, providing significantly lowered the number of apoptotic germ cells and improved morphometric and stereological testicular parameters (Okada et al, 2009).…”

“…In previous studies using L-carnitine pre-treatment, our group showed a significantly lower incidence of apoptosis in germ cell caused by etoposide (Okada et al, 2009), pointing out for a broader usage of this compound. Considering those results, this study aimed to investigate whether carnitine pre-treatment protects the pre-pubertal seminiferous epithelium from the damages induced by doxorubicin and whether such protection can lead to an improvement in spermatic parameters and testicular integrity in the adult phase.…”

“…Indeed, our group has been showing that chemotherapeutic treatments during pre-puberty can lead to irreversible damage to the seminiferous epithelium of rats, although some degree of spermatogenesis restoration is frequently observed (Stumpp et al, 2004;Okada et al, 2009;Vendramini et al, 2010Vendramini et al, , 2012Brilhante et al, 2011Brilhante et al, , 2012. Among the chemotherapeutic drugs studied, etoposide (Stumpp et al, 2004;Okada et al, 2009) and doxorubicin (Vendramini et al, 2010(Vendramini et al, , 2012Brilhante et al, 2011Brilhante et al, , 2012 appear to be particularly aggressive to the reproduction.…”

“…Indeed, the search for protocols that reduce the reproductive side-effects of chemotherapy has been the main goal of studies using experimental models (Lirdi et al, 2008;Okada et al, 2009;Vendramini et al, 2010;Chao et al, 2011). Carnitine, an important quaternary amine (3-hydroxy-4-N,N,N-trimethylaminobutyrate), is an essential nutrient with a major role in cellular energy production and has been considered a promising cytoprotective agent (Sayed-Ahmed, 2010).…”

Cancer Induced Infertility and the Role of L-Carnitine: A Review for Possible Future Clinical Applications

“…In comparison to etoposide group, co-administration with LC ameliorated histological and histomorphometrical alterations, concentration of spermatozoa, and sperm abnormal morphology. However, the authors thought that proving the injurious effects of etoposide in pre-pubertal condition is the most achieved findings, and the protective effects of LC must be confirmed in further investigation (34).…”