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

Area of Science:

• Pharmacology
• Cardiovascular Research
• Oncology Supportive Care

Background:

• Imatinib (IM), a tyrosine kinase inhibitor, is crucial for cancer treatment.
• IM can induce cardiotoxicity, a significant side effect impacting patient outcomes.
• Understanding protective mechanisms against IM-induced cardiac damage is vital.

Purpose of the Study:

• To investigate the cardioprotective effects of l-carnitine against Imatinib-induced cardiotoxicity in a rat model.
• To elucidate the molecular pathways involved in l-carnitine's protective action.

Main Methods:

• Male albino rats were administered Imatinib (40 mg/kg) alone or with l-carnitine (100 mg/kg) for 7 days.
• Biochemical markers (cytokines, MDA, NO, SOD, GSH), cardiac signaling pathways (MAPK, PPAR-γ), and gene expression (Bcl-2, BAX, PDGF, CTGF) were analyzed.
• Histopathological examination and serum/intracellular drug concentration measurements were performed.

Main Results:

• Imatinib induced significant cardiotoxicity, evidenced by increased inflammatory cytokines, oxidative stress (MDA, NO), and altered cardiac signaling.
• IM treatment decreased protective factors (PPAR-γ, SOD, GSH, Bcl-2, PDGF) while increasing pro-apoptotic markers (CTGF, BAX).
• L-carnitine administration ameliorated these detrimental effects, improving biochemical and histopathological parameters without altering IM serum levels.

Conclusions:

• L-carnitine effectively abrogates Imatinib-induced cardiac damage and apoptosis in rats.
• The protective mechanism involves the modulation of PDGF/PPARγ/MAPK signaling pathways.
• L-carnitine represents a promising therapeutic agent for managing Imatinib-related cardiotoxicity.