Syringic acid exhibits ameliorative effects against cyclosporine A-induced cardiotoxicity in mice by mitigating oxidative stress, inflammatory response, and apoptotic cell death.

Cyclosporine A (CsA) is a commonly used drug to inhibit graft rejection and treat a variety of autoimmune diseases. Cardiotoxicity is one of the most serious undesirable effects of CsA which has limited its clinical use. Syringic acid (SA) is a polyphenolic compound with several striking biological influences. The current study aimed to investigate the ameliorative activity of SA against CsA-induced cardiotoxicity. Forty male mice were allocated into five groups: control (normal saline) group, CsA (30 mg/kg, s.c.) group, SA (25, 50, and 100 mg/kg, i.p.) + CsA groups. Animals received the drugs for 21 days and pretreatment with SA was carried out one hour prior to CsA injection. Results demonstrated that CsA remarkably enhanced the activities of AST, CK-MB, and LDH as well as the serum level of troponin I. CsA triggered oxidative stress by elevating the levels of cardiac oxidants, MDA and NO and reducing the activities of cardiac antioxidants, SOD and GPx. Furthermore, CsA significantly increased the protein expression of cardiac pro-inflammatory cytokines, TNF-α and IL-1β. CsA markedly provoked cardiac apoptosis by upregulating the protein expression of Bax and cleaved caspase-3 and downregulating the protein expression of Bcl-2. The histopathological evaluations validated the above-mentioned findings. However, all these alterations were considerably mitigated in SA-treated mice. These data highlight the fundamental role of oxidative stress, inflammation, and apoptosis in CsA-mediated cardiotoxicity that significantly suppressed by administration of SA. Therefore, SA can act as a promising cardioprotective agent to effectively prevent CsA-induced cardiac injury.