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

• MSG induced significant cardiotoxicity through SERCA2a downregulation, calcium dysregulation, and oxidative stress in male Wistar rats. • L-arginine treatment restored SERCA2a expression and normalized plasma and cardiac calcium homeostasis in MSG-treated animals. • L-arginine enhanced antioxidant defense mechanisms by increasing NADPH, G6PDH, and GPx activities while reducing lipid peroxidation. • MSG dysregulated VEGF-PI3K growth factor signaling, while L-arginine normalized these pathways to prevent apoptosis. • L-arginine demonstrated multi-target cardioprotection through simultaneous modulation of calcium handling, redox balance, and survival signaling pathways. 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 100-120g 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 (120mg/kg) + vehicle, group 4; MSG+ L-Arginine daily for 6 weeks respectively. At the end of the experiment, rats were anaesthetized with 0.3ml 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 p-values < 0.05 accepted as significant. The results showed that MSG, compared with the control, significantly decreased plasma and cardiac NO, NADPH, GPx, Ca2+, cardiac SERCA2 activity, VEGF, and PI3K, and increased plasma and cardiac MDA and uric acid (P