Abstract
<title>Abstract</title> <p> <bold>Background:</bold> Benzo[a]pyrene is a dietary carcinogen in grilled and smoked foods that causes multiorgan toxicity via oxidative stress. Despite the traditional consumption of <italic>Rhus coriaria L</italic> . (Sumac) with BaP-rich foods, no study has addressed the protective efficacy of Sumac against BaP-induced toxicity and its superiority over vitamin E. Therefore, the present study aimed to investigate these aspects. <bold>Methods:</bold> Seventy male C57BL/6 mice were randomly assigned to 14 groups: control, BaP (20 mg/kg), BaP + vitamin E (250 mg/kg), and BaP + hydroalcoholic extract of Sumac at three doses (50, 150, and 300 mg/kg), which were administered under two separate regimens, coadministration (therapeutic model) and pretreatment (prophylactic model). After 4 weeks, oxidative stress markers, hepatorenal function, lipid profiles, testosterone levels, sperm quality parameters (motility, concentration, DNA integrity, chromatin status, and oxidative indices), and histopathology of the liver and kidney were evaluated. <bold>Results:</bold> BaP exposure significantly increased the levels of MDA, liver enzymes (ALT, AST, and ALP), total bilirubin, BUN, and creatinine; dyslipidemia; sperm DNA damage; sperm lipid peroxidation; protamine deficiency; and intracellular ROS while decreasing the TAC, albumin, testosterone, and total and progressive sperm motility. Vitamin E has shown limited efficacy, improving only the levels of albumin, cholesterol, LDL, and BUN; sperm lipid peroxidation; and protamine deficiency while failing to affect the levels of oxidative markers, liver enzymes, bilirubin, triglycerides, creatinine, and testosterone; and most sperm quality parameters. In contrast, the Sumac extract, especially at higher doses (150 and 300 mg/kg), dose-dependently restored the antioxidant status, normalized liver and kidney function, corrected the lipid profile, and significantly improved chromatin integrity and sperm motility. These effects were markedly more pronounced with the prophylactic regimen than with the therapeutic regimen. Notably, while Sumac coadministration induced only mild hepatocellular degeneration, the pretreatment regimen unexpectedly led to severe hepatocellular degeneration, despite normal or decreased serum liver enzyme levels. This apparent contradiction is explained by the key physiological principle that liver enzyme leakage occurs only in necrosis (membrane damage) and not in degeneration (membrane integrity preservation). Therefore, normal serum liver enzyme levels are by no means equivalent to those of healthy liver tissue. Furthermore, Sumac significantly reduced BaP-induced proliferative glomerulonephritis and tubular degeneration in the kidney. <bold>Conclusion:</bold> The Sumac extract is superior to vitamin E in preventing BaP-induced systemic and reproductive toxicity because it reduces oxidative stress, preserves sperm chromatin, improves hepatorenal function, and corrects the lipid profile. These findings support Sumac as an effective, safe, and accessible dietary chemopreventive agent. </p>