Pomiferin Protects against Sepsis-Associated Acute Liver and Kidney Injury via Inhibition of NF-κB Activation, Oxidative Stress, and Cytochrome-c

Abstract

In this study we report the first identification of the therapeutic effects of pomiferin isolated from Maclura pomifera against acute liver and kidney injury induced by sepsis. These results were obtained using a rat model of sepsis. We focused on targeting the nuclear factor kappa B (NF-kappa B) activation cascade, oxidative stress, and cytochrome-c, three key components involved in the pathophysiology of sepsis-associated acute liver and kidney injury. This assessment was conducted using biochemical, histopathological, immunohistochemical, and immunofluorescence analyses to examine parameters in liver and kidney tissues. The cecal ligation and puncture technique, used to induce sepsis, consistently caused acute liver and kidney damage. This was evidenced by significant increases (p < 0.0001), relative to untreated control rats, in the abundance of Toll-like receptor 4, NF-kappa B p65, phospho-NF-kappa B p65, 8-hydroxydeoxyguanosine, cytochrome-c, and caspase-3, higher degeneration, lipid peroxidation, and necrosis. This technique also caused significant decreases (p < 0.001) in components of the cellular antioxidant system in the hepatic and renal tissues of septic rats. Pomiferin, particularly at a dose of 300 mg/kg, showed promising pharmacological effects by reversing these pathological changes. Overall, pomiferin appears to protect liver and kidney tissues during sepsis by suppressing the NF-kappa B activation cascade, reducing oxidative stress, and lowering cytochrome-c activity. These effects suggest that pomiferin may be useful for managing sepsis patients with acute liver and kidney injury.