The protective effect of acetyl l-carnitine to gonadotoxic effect of cisplatin on uterus

Cisplatin that is used effectively in chemotherapy, takes place in the treatment of several tumors which are seen in adulthood and many childhood tumors such as neuroblastoma, Wilms tumor, hepatoblastoma, brain tumors, germ cell tumors, osteosarcoma. Along with proven gonadotoxic effect of Cisplatin, it has been shown through various studies that it has side effects on several systems. Nephrotoxicity, neuropathy, ototoxicity and gonadotoxicity are important clinically dose-limiting side effects of Cisplatin. After Cisplatin enters the cell, many signal transduction pathways become active and it causes the cell apoptosis, necrosis, oxidative stress, fibrogenesis, inflammation, hypoxia and by leading to mitochondrial damage shows cytotoxic effect.In this study, applications of Cisplatin, whose gonadotoxic effect is known, changes in the uterine tissue has been detected and to prevent these changes Acetyl L-Carnitin's protective effect has been investigated. To this purpose, for histomorphological analysis hematoxylin-eosin (H&E) staining, to observe DNA fragmentation TUNEL assay and to determine apoptotic effects, anti Caspase 3, 8 and 9 antibodies were applied.In the study, pre-experiment and post-experiment average weights of rats were evaluated. Although weight loss has been observed in both the pre-treated and Cisplatin groups, the loss in the latter one proved to be more than the former one.In histological examinations, in Cisplatin group in the endometrial as intraepithelial and in subepithelial connective tissue, existence of inflammatory cell infiltration has been observed and in the lumen of endometrial glands, cellular debris and edema in the subepithelial connective tissue were observed. Also, it has been spotted that by changing morphological character the uterine epithelium has turned into squamous epithelium. When the pre-treated group with Acetyl L-Carnitin+Cisplatin is compared with Cisplatin group, it is determined that, the cellular debris are almost never observed in the lumen of the endometrial glands, subepithelial and intraepithelial lymphocytes are rarely existent in the endometrium and edema are not formed.While in Cisplatin group, in the uterine epithelia there were many DNA fragmentations; in Acetyl L-Carnitin+Cisplatin pre-treated group this number was less. This is interpreted as pre-treatment practice has prevented DNA fragmentation.Immunohistochemical results of Caspase 8 and 9, that were applied in order to spot which apoptotic pathway has been stimulated as a result of Cisplatin use, showed that apoptosis has been stimulated with both pathways as extrinsic and intrinsic. But it is determined that the proapoptotic cell numbers that go into apoptosis with extrinsic pathway stimulated with Caspase 8 are higher than the cell numbers stimulated by intrinsic pathway.In the conclusion of the study, the toxic effect of Cisplatin upon uterus, which is proven by histomorphological and apoptotic findings, is found to be prevented with the prophylactic use of Acetyl L-Carnitin.