Arsenic can induce lethal hepatorenal insufficiency by inducing progressive cytotoxicity in the two main body\\\'s hemostatic regulators, the kidney and liver. In the current study, the hepatorenal protective impact of caffeic acid was investigated in arsenic-exposed Syrian mice. Twenty-four male Syrian mice (30 ± 8 g) were provided and randomly divided into 4 groups of 6 receiving nothing, arsenic, arsenic and caffeic, and caffeic acid. The mice passed the 21-day treatment program. The mice\\\'s blood was collected and analyzed by measuring the serum ALT/AST enzymes and creatinine/urea levels, respectively. Finally, the histopathological properties in both the kidney and liver organs of the mice were studied. Arsenic administration significantly increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), LDH, urea, and creatinine concentrations (p < 0.05). Simultaneous administration of caffeic acid with arsenic decreased the serum AST and creatinine (p < 0.05). Moreover, the renal glomerulus and liver regeneration in the mice receiving caffeic acid supplements exhibited the caffeic acid hepatorenal protective potential. The histopathological changes caused by arsenic in the mice\\\'s liver and kidney tissue including degeneration, necrosis, hyperemia, and tissue hypotrophy were shifted to normal conditions following the caffeic acid administration dose, which was verified by the mice blood biochemical analysis results.

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