Investigation of the Protective Effects of Acetyl L-Carnitine on Cisplatin-Induced Uterus Toxicity
AbstractObjective: The aim of the study was to investigate the prophylactic effects of acetyl L-carnitine against to uterus induced by cisplatin. Methods: Twenty-four female Wistar albino rats were divided into four groups: group I (control) was administered with saline; group II was administered with acetyl L-carnitine; group III was administered with cisplatin; group IV was pretreated with acetyl L-carnitine before cisplatin intraperitoneal injection. After 72h of cisplatin injection uterine tissue was removed. Histological and immunohistochemical investigations were performed, respectively. Results: We found that the number of TUNEL and caspases positive cells were increased in the endometrial epithelium, subepithelial connective tissue, endometrial glands and stroma in group III compare to the other groups. Furthermore inflammation and edema were observed in uterus of rats in group III. Conclusion: We can concluded that pretreatment of acetyl L-carnitine administration has protective effect on histological alteration of uterus caused by cisplatin.
Sonmezer M, Ozkavukcu S. Fertility preservation in females with malignant disease-1: causes, clinical needs and indications. Turk J Haematol 2009; 26:106-13.
Familiari G, Caggiati A, Nottola SA, Ermini MD, Benedetto MR, Motta PM. Ultrastructure of human ovarian primordial follicles after combination chemotherapy for Hodgkin’s disease. Hum Reprod 1993; 8 (12): 2080-7.
Fadillioglu E, Erdogan H, Sogut S, Kuku I. Protective effects of erdosteine against doxorubicin-induced cardiomyopathy in rats. J Appl Toxicol 2003; 23: 71-4.
Fadillioglu E, Erdogan H. Effects of erdosteine treatment against doxorubicin-induced toxicity through erythrocyte and plasma oxidant/ antioxidant status in rats. Pharmacol Res 2003; 47: 317-22.
DeVita VT, Hellman S, Rosenberg SA, editors. Cancer, principles & practice of oncology. 7th ed. Philadelphia: A Wolters Kluwer Co; 2005: 295-306.
Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 2007; 7: 573-84.
Sonmezer M, Oktay K. Fertility preservation in female patients. Hum Reprod Update 2004; 10: 251-66.
Warne GL, Fairley KF, Hobbs JB, Martin Fl. Cyclophoshamide-induced ovarian failure. N Engl J Med 1973; 289: 1159-62.
Mackie EJ, Radford M, Shalet SM. Gonadal function following chemotherapy for childhood Hodgkin’s disease. Med Peidatr Oncol 1996; 27: 74-8.
Delibas N, Ozcankaya R. Serbest Radikaller. SDÜ Tıp Fakültesi Dergisi 1995; 2: 11-17.
Kalinec GM, Fernandez-Zapico ME, Urrutia R, Esteban-Cruciani N, Chen S, Kalinec F. Pivotal role of Harakiri in the induction and prevention of gentamicin-induced hearing loss. Proc Natl Acad Sci U S A 2005; 102: 16019-24.
Gülçin I. Antioxidant activity of caffeic acid (3,4-dihydroxycinnamic acid). Toxicology. 2006; 217: 213-20.
Al-Majed AA. Carnitine deficiency provokes cisplatin-induced hepatotoxicity in rats. Basic Clin Pharmacol Toxicol 2007; 100: 145-50.
Pacifici EH, McLeod LL, Sevanian A. Lipid hydroperoxide-induced peroxidation and turnover of endothelial cell phospholipids. Free Radic Biol Med 1994; 17: 297-309.
Madesh M, Balasubramanian KA. Activation of liver mitochondrial phospholipase A2 by superoxide. Arch Biochem Biophys 1997; 346: 187-92.
Tufekci O, Gunes D, Ozogul C, Kolatan E, Altun Z, Yılmaz O, et al. Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity. Chemotherapy 2009; 55: 451-9.
Coskun N, Hatipoglu MT, Ozogul C, Korkmaz C, Akyol SN, Micili SC, et al. The protective effects of acetyl L-carnitine on testis gonadotoxicity induced by cisplatin in rats. Balkan Med J 2013; 30: 235-41.
Rosenberg B. Fundamental studies with cisplatin. Cancer 1985; 55: 2303-16.
Zhang X, Yamamoto N, Soramoto S, Takenaka I. Cisplatın-induced germ cell apoptosis in mouse testes. Arch Androl 2001; 46: 43-9.
Molmann JE, Glover DJ, Hogan WM, Furman RE. Cisplatin neuropathy: Risk factors, prognosis, and protection by WR-2721. Cancer 1988; 61: 2192-5.
Screnci D, Mckeage MJ. Platinum neurotoxicity: Clinical profiles, experimental modelsand neuroprotective approaches. J Inorg Biochem 1999; 77: 105-10.
Sugiyama S, Hayakawa M, Kato T, Hanaki Y, Shimizu K, Ozawa T. Adverse effect of anti-tumor drug, cisplatin, on rat kidney mitochondria: disturbances in glutathione peroxidase activity. Biochem Biophys Res Commun 1989; 159: 1121-7.
Kuhlmann MK, Burkhardt G, Köhler H. Insights into potential cellular mechanisms of cisplatin nephrotoxicity and their clinical application. Nephrol Dial Transplant 1997; 12: 2478-80.
Plowchalk DR, Meadows MJ, Mattison DR. Reproductive toxicity of cyclophosphamide in the C57BL/6N mouse: 2. Effects on uterine structure and function. Reprod Toxicol 1992; 6: 423-9.
Iraz M, Ozerol E, Gulec M, Tasdemir S, Idiz N, Fadillioglu E, et al. Protective effect of caffeic acid penethyl ester (CAPE) administration on cisplatin-induced oxidative damage to liver in rat. Cell Biochem Funct 2006; 24: 357-61.
Ali BH, Al Moundhri MS. Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: A review of some recent research. Food Chem Toxicol 2006; 44: 1173-83.
Arockia Rani PJ, Panneerselvam C. Carnitine as a free radical scavenger in aging. Exp Gerontol 2001; 36 (10): 1713-26.
Vanella A, Russo A, Acquaviva R, Campisi A, Di Giacomo C, Sorrenti V, et al. L -propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage protector. Cell Biol Toxicol 2000; 16: 99-104.
Chang B, Nishikawa M, Sato E, Utsumi K, Inoue M. L-Carnitine inhibits cisplatin-induced injury of the kidney and small intestine. Arch Biochem Biophys 2002; 405: 55-64.
Saribas GS, Erdogan D, Goktas G, Akyol SN, Hirfanoglu IM, Gurgen SG, et al. Examining the protective effects of acetyl l-carnitine on cisplatin-induced uterine tube toxicity. J Obstet Gynaecol 2016; 36: 1086-92.
Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int 2008; 73: 994-1007.
All opinions and reports within the articles that are published in the Gazi Medical Journal are the personal opinions of author(s). Gazi University, Editors and the publisher do not accept any responsibility for these articles. The journal is printed on acid-free paper.