EJMS

Abstract

Background L-carnitine represents a valuable adjuvant for MSCs pre-treatment due to its anti-inflammatory, antioxidant, and anti-apoptotic effects on injured cardiomyocytes. Yet, limited studies were implemented to investigate their combined influence on cardiomyocyte regenerative factors. Therefore, the present study aimed to explore the combined role of L-carnitine-pre-treated MSCs on the modulation of the proliferative mediator Ki-67 and the cardiac differentiation factor tyrosine hydroxylase and their impact on cardiac toxicity induced by Doxorubicin (DOX). Materials and Methods Rats were divided into group I (control), group II (DOX), group III (DOX+MSCs), group IV (DOX+L-carnitine), group V (DOX+L-carnitine pre-treated MSCs). Light microscopic examination was done to assess the histopathological changes in the cardiomyocyte architecture and the immunohistochemical reactions of Ki-67, TH, and hsp90. Biochemical and QRT-PCR studies were performed to evaluate the cardiac enzymes, caspase-3, NF-kβ, IL 1b, MDA, catalase, TNF-α, and Bcl2. Results L-carnitine pre-treated MSCs group showed overexpression of the proliferative indicator Ki-67 and the cardiac differentiation marker TH which play an important role in cardiomyocyte regeneration and repair. These findings are associated with the regain of the normal architecture of the cardiomyocytes and adjustment of the levels of CK-MB, troponin I, MDA, and catalase. Ki-67 and TH regenerative capacity was associated with the regulation of the immunomodulators; NF-ҡβ, TNFα, IL-1β, hsp90, and the apoptotic regulators; caspase 3 and Bcl2. Conclusions Pre-treatment of MSCs with L-carnitine enhances the proliferation and differentiation capacities of Ki-67 and TH with regulation of the inflammatory and apoptotic factors, representing a promising therapy for cardiac diseases.