Rutin mitigates perfluorooctanoic acid-induced liver injury via modulation of oxidative stress, apoptosis, and inflammation

Abstract

Objective(s): Perfluorooctanoic acid (PFOA) is a persistent organic pollutant (POP), broadly present in the environment. Due to long biological half-life, it is accumulated in the body, especially the liver, causing hepatocellular damage. This study was designed to assess the effects of rutin on PFOA-induced liver damage in rats.Materials and Methods: Male Wistar rats were exposed to PFOA (10 mg/kg/day) alone, or in combination with different doses of rutin (25, 50, and 100 mg/kg/day) by oral gavage for 4 weeks. Results: PFOA altered the levels of liver enzymes, induced a notable change in the tissue structure of the liver, caused some levels of mitochondrial dysfunction, and increased the expression of pro-apoptotic and pro-inflammatory genes. Co-treatment with rutin mitigated the PFOA-induced elevation of liver enzymes, histopathological defects, oxidative damage, and mitochondrial dysfunction. In addition, rutin declined the stimulatory effects of PFOA on the Bax: Bcl2 ratio and reduced the PFOA-induced gene expression of TNF-α, IL-6, NF-ƙB, and JNK.Conclusion: These findings suggest rutin as a protective agent for PFOA-induced liver injury, albeit the protection was partial. Possible mechanisms are inhibition of oxidative stress, mitochondrial dysfunction, and inflammatory response.

Keywords

• apoptosis
• hepatotoxicity inflammation
• oxidative stress
• perfluorooctanoic acid
• rutin