EFFECTS OF SYRINGIC ACID PRE- AND POST-TREATMENTS ON CISPLATIN- INDUCED CARDIOTOXICITY IN MALE WISTER RATS

Plant-based compounds are known for various pharmacological properties. One of them is syringic acid (SAC), which possesses strong antioxidant and anti-inflammatory properties. These properties make SAC a suitable co-drug candidate to combat various chemotherapy- induced side effects. Thus, we investigated the effect of SAC treatments on cisplatin (CISP)- induced cardiotoxicity in male Wistar rats, employing both computational and in vivo approaches. For the latter, 50 mg/kg of CISP was administered intraperitoneally twice in 5 days, followed by 50 mg/kg oral SAC pre- and post-treatments for 14 days. The outcome of the in silico molecular docking study showed a strong binding affinity (-4.5 kcal/mol) of SAC to the active site of the antioxidant enzyme – superoxide dismutase compared to a known activator of the enzyme with binding affinity of -4.6 kcal/mol. In the in-vivo experiment, CISP- induced hematotoxicity was characterised by a significant increase in the PCV, RBC, Hb, and WBC counts compared with the control. Also, CISP-induced cardiotoxicity was characterized by a significant increase in heart levels of H2O2, IL-6, TNF-α, Nrf2, and Akt/PKB, as well as heart activities of GST, SOD, and significantly decreased the cardiac CAT activity and PI3K level compared with the control group. Both pre- and post-treatments with SAC demonstrated similar effects on the CISP-induced cardiotoxicity and hematotoxicity by reversing the observed toxicity. Based on these outcomes, we concluded that the mechanism by which SAC mitigated the CISP-induced cardiotoxicity and hematotoxicity is via its antioxidant property capable of activating SOD to dismutate the superoxide radical to H2O2, and the detoxification of H2O2 by CAT to water and oxygen