Carnitine partially improves oxidative stress, acrosome integrity, and reproductive competence in doxorubicin-treated rats.

Doxorubicin has been largely used in anticancer therapy in adults, adolescents, and children. The efficacy of l-carnitine as an antioxidant substance has been confirmed both in humans and rats. Carnitine, present in testis and epididymis, is involved in sperm maturation. It is also effective in infertility treatment. As a continuation of a previous study, we evaluated whether some spermatic qualitative parameters, DNA integrity, chromatin structure, and fertility status, could be ameliorated by the carnitine treatment in adult rats, which were subsequently exposed to doxorubicin at pre-puberty. Pre-pubertal male rats were distributed into four groups: Sham Control; Doxorubicin; l-carnitine; l-carnitine + Doxorubicin (l-carnitine injected 1 h before doxorubicin). At 100 days of age, all groups were reassigned into two sets: One set was submitted to the evaluation of sperm motility, acrosome integrity, mitochondrial activity, sperm chromatin structure analysis (SCSA), and evaluation of the oxidative stress. The other set of rats was destined to the evaluation of reproductive competence. The percentage of spermatozoa with intact acrosome integrity was higher in the Carnitine+Doxorubicin group when compared with the Doxorubicin group. However, sperm motility and mitochondrial activity were not improved by carnitine pre-treatment. Both values of malondialdehyde and nitrite (indirect measurement of nitric oxide) concentrations were statistically higher in the only doxorubicin-treated group when compared to the Carnitine + Doxorubicin group. Fertility index and implantation rate were lower in Doxorubicin group, when compared to Carnitine + Doxorubicin group. Moreover, the percentage of spermatozoa with damaged DNA was higher in the Doxorubicin-treated group when compared to the Carnitine+Doxorubicin group. l-carnitine, when administered before doxorubicin, partially preserved the acrosome integrity, an important feature related to sperm fertilization ability that positively correlated with the reproductive competence and sperm DNA integrity at adulthood. In conclusion, l-carnitine attenuated the long-term alterations caused by doxorubicin in the germ cells and improved male reproductive capacity in adulthood.

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

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 1 h before doxorubicin). The rats were submitted to euthanasia at 64 and 100 days 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 (100 days), 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 64 days, the TUNEL-positive germ cell frequency was lower in the carnitine/doxorubicin-treated rats comparatively to the doxorubicin-treated rats. At 100 days 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.