L-arginine attenuates downregulated SERCA2a activity via enhanced PI3K/ VEGF signalling in monosodium glutamate-induced cardiac toxicity of male Wistar rats

Abstract

L-arginine is a semi-essential amino acid that is produced endogenously and can be obtained through dietary supplements. Monosodium glutamate (MSG) is an umami flavor enhancer used in packaged and processed food and has been associated with cardiotoxicity and inflammation. The sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) is a key player in the Ca2+ cycle of cardiac regulation. This study aims to evaluate the effect of L-arginine on SERCA2a in MSG-induced cardiac toxicity. Twenty male Wistar rats weighing 100–120 g were divided into four groups (n = 5/group) and were fed as group1; control- rat chow + olive oil (vehicle); group 2; rat chow+ L-arginine (150 mg/kg), group 3; MSG (120 mg/kg) + vehicle, group 4; MSG+ L-Arginine daily for 6 weeks respectively. At the end of the experiment, rats were anaesthetized with 0.3 ml of I.M ketamine hydrochloride (50mg/ml), and blood was collected by cardiac puncture. Serum and cardiac tissue homogenate were analyzed, and values expressed as mean ± SEM with pvalues < 0.05 accepted as significant. The results showed that MSG, compared with the control, significantly decreased plasma and cardiac NO, NADPH, GPx, Ca2+, cardiac SERCA2a activity, VEGF, and PI3K, and increased plasma and cardiac MDA and uric acid (P < 0.05). However, L-arginine significantly increased NO, NADPH, GPx, and cardiac SERCA2a activity, as well as VEGF and PI3K, compared with the control and MSG-treated groups. In conclusion, L-arginine attenuated MSG-induced cardiotoxicity by restoring calcium handling and redox balance, as well as modulating VEGF–PI3K/Akt survival signaling to reduce apoptotic and metabolic dysfunctions.