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

Abstract

Doxorubicin, an anticancer drug, is widely included in chemotherapy protocols to combat childhood cancer. Carnitine, an important quaternary amine, is present in testis and epididymis and is involved in sperm maturation; it has been used in infertility treatment. in a previous study, our group observed that l-carnitine given before etoposide, another chemotherapeutic drug, reduces the spermatogenic damage and protects germ cells against apoptosis. This study aimed to evaluate the antiapoptotic and cytoprotective actions of l-carnitine in long- and mid-term basis, on the seminiferous epithelium of doxorubicin-treated pre-pubertal rats. Forty-eight 30-day-old male Wistar rats were distributed into four groups: sham-control; doxorubicin; carnitine; carnitine/doxorubicin (l-carnitine injected 1h before doxorubicin). the rats were submitted to euthanasia at 64 and 100days of age and their testes were collected for biometric, morphometric, and histopathological analyses. the numerical density of apoptotic germ cells was obtained (TUNEL method). in adult phase (100days), the following spermatic parameters were analyzed: mature spermatid (19 step) count and sperm daily production per testis; sperm number and transit time through the epididymal caput/corpus and cauda; frequency of morphologically abnormal spermatozoa (from epididymal fluid), as well as sperm DNA integrity (Comet assay). the testicular and spermatic parameters at both ages were improved in rats treated with carnitine before doxorubicin. At 64days, the TUNEL-positive germ cell frequency was lower in the carnitine/doxorubicin-treated rats comparatively to the doxorubicin-treated rats. At 100days of age, the sperm DNA fragmentation was also lower in the previously carnitine-treated rats, as evidenced by the analysis of three parameters. Carnitine reduced the late testicular and spermatic damages caused by doxorubicin, probably providing a partial cytoprotection against the deleterious action of doxorubicin administration to pre-pubertal rats. However, further studies shall be undertaken to investigate the protective mechanisms involved in such germ cell preservation.