Effect of l-carnitine on cardiotoxicity and apoptosis induced by imatinib through PDGF/ PPARγ /MAPK pathways.

A tyrosine kinase inhibitor Imatinib (IM) is used in the treatment of different varieties of cancers. The current study was designed to explore the beneficial role of l-carnitine against IM-induced cardiotoxicity in rats. Male albino rats received IM (40 mg/kg, i.p.) either alone or/in combination with l-carnitine (100 mg/kg, i.p.) for 7 days. IM increased serum inflammatory cytokines, concomitant with activation of cardiac MAPK, α-SMA, malondialdehyde (MDA) and nitric oxide(NO), decreased cardiac peroxisome proliferator-activated receptor-γ (PPAR-γ) level, superoxide dismutase (SOD) activity, and glutathione (GSH) content. The expression levels of Bcl-2 and PDGF were significantly decreased, while the expression levels of CTGF and BAX were significantly increased in the IM group. The l-carnitine treatment successfully protected the heart as indicated by the improvement of the biochemical and histopathological parameters. l-carnitine didn't affect the serum concentration of IM and increased intracellular concentration in the combination-treated group as measured by the mass spectrometer.
Conclusion: l-carnitine abrogated IM-induced cardiac damage and apoptosis via PDGF/PPARγ/MAPK pathways.