Tomato Polyphenols Protect Human Red Blood Cells from Mercury-Induced Oxidative Stress and Phosphatidylserine Exposure

Oxidative stress plays a central role in the development of cardiovascular diseases (CVDs) and is strongly influenced by environmental toxicants such as heavy metals. Mercury (Hg) is a well-known pro-oxidant agent capable of disrupting cellular redox homeostasis, pro-moting reactive oxygen species (ROS) generation, and inducing structural and functional alterations in circulating blood cells. In particular, erythrocytes (RBC) are highly suscep-tible to oxidative damage due to their continuous exposure to oxygen and limited antiox-idant repair mechanisms. In this study, we investigated the protective effects of polyphe-nolic extracts obtained from two tomato (Solanum lycopersicum) cultivars, Piccadilly and Piennolo, against HgCl2-induced oxidative stress in human RBC. Chemical characteriza-tion revealed that Piennolo extracts contained higher levels of total polyphenols, flavo-noids, and ortho-diphenols compared with Piccadilly samples. Despite these differences, both extracts showed comparable antioxidant capacity. In RBC exposed to HgCl2, tomato extracts significantly reduced ROS production, lipid peroxidation (TBARS), methemoglo-bin formation, and sulfhydryl depletion, while restoring intracellular glutathione levels. Importantly, pretreatment with the extracts markedly decreased phosphatidylserine ex-ternalization, indicating preservation of membrane phospholipid asymmetry and a re-duction in the procoagulant phenotype induced by oxidative stress. Overall, these find-ings suggest that bioactive compounds present in polyphenol-rich tomato extracts exert protective effects on RBC through antioxidant and membrane-stabilizing mechanisms