Antioxidant effect of acetyl-l-carnitine against cisplatin-induced cardiotoxicity


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Bayrak S., Aktaş S., Altun Z. S., Cakir Y., Tutuncu M., Ozsengezer S. K., ...More

JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, vol.48, no.8, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 48 Issue: 8
  • Publication Date: 2020
  • Doi Number: 10.1177/0300060520951393
  • Journal Name: JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: Cisplatin, cardiotoxicity, acetyl-L-carnitine, superoxide dismutase-2, immunohistochemistry, xenograft, mice, antioxidant, CHEMOTHERAPY, STRESS, OTOTOXICITY, MECHANISMS
  • Dokuz Eylül University Affiliated: Yes

Abstract

Objective Cisplatin (CDDP) toxicity is a dose-limiting clinical problem in clinical practice, mainly because of nephrotoxicity or ototoxicity. However, the mechanism of CDDP-induced cardiotoxicity is poorly understood. Acetyl-l-carnitine (ALCAR) is an antioxidant agent with protective effects against the side effects of various chemotherapeutics. CDDP-induced cardiotoxicity and the protective role of ALCAR were evaluated in this study. Methods Morphological changes were evaluated in hematoxylin and eosin-stained sections, and immunohistochemistry for caspase-3, superoxide dismutase-2 (SOD-2), inducible nitrite oxide synthase (iNOS), cyclooxygenase-2, and Bcl-2 was performed using the hearts of athymic nude mice carrying xenograft neuroblastoma tumors. Mice were randomized (six/group) to the control, CDDP (16 mg/kg), and ALCAR (200 mg/kg)+CDDP (16 mg/kg) groups. Results were analyzed using nonparametric tests. Results No difference was observed in the rates of cardiac necrosis, dilated/congested blood vessels, hemorrhage, polymorphonuclear leukocyte infiltration, edema, and pyknotic nuclei among the groups. SOD-2 expression was increased in the CDDP group but not in the ALCAR+CDDP group. iNOS, Bcl-2, and caspase-3 levels were not significantly different among the groups. Conclusions ALCAR might be a candidate protective agent for CDDP-induced cardiotoxicity. SOD-2, as a member of the oxidant system, should be evaluated in further studies as a biomarker of cardiotoxicity.