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, promoting reactive oxygen species (ROS) generation, and inducing structural and functional alterations in circulating blood cells. In particular, erythrocytes (RBC) are highly susceptible to oxidative damage due to their continuous exposure to oxygen and limited antioxidant repair mechanisms. In this study, we investigated the protective effects of polyphenolic extracts obtained from two tomato (Solanum lycopersicum) cultivars, Piccadilly and Piennolo, against HgCl2-induced oxidative stress in human RBC. Chemical characterization revealed that Piennolo extracts contained higher levels of total polyphenols, flavonoids, 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), methemoglobin formation, and sulfhydryl depletion, while restoring intracellular glutathione levels. Importantly, pretreatment with the extracts markedly decreased phosphatidylserine externalization, indicating preservation of membrane phospholipid asymmetry and a reduction in the procoagulant phenotype induced by oxidative stress. Overall, these findings suggest that bioactive compounds present in polyphenol-rich tomato extracts exert protective effects on RBC through antioxidant and membrane-stabilizing mechanisms.