Fertaric Acid Protects from Octylphenol-Related Hepatotoxicity in Rats: Biochemical, Molecular, and Histopathological Studies.

The endocrine-disrupting chemical 4-tert-octylphenol (OP) can mimic estrogen and testosterone hormones and threaten health; fertaric acid (FA) is a hydroxycinnamic acid found in grapefruit. This study aimed to investigate whether FA has a protective effect on 4-tert-octylphenol-related hepatotoxicity. Thirty male albino rats were divided into 5 equal groups of 6 rats each as follows: control group-administrated orally with 1 ml saline 3 days/week for 4 weeks; corn oil group-administrated orally with 1 ml corn oil 3 days/week for 4 weeks; FA-treated group-administrated orally with FA (45 mg /kg body weight) dissolved in saline 3 days/week for 4 weeks; OP-treated group-administrated orally with OP (40 mg /kg body weight) dissolved in corn oil 3 days/week for 4 weeks; FA + OP-treated group-administrated orally with FA (45 mg /kg body weight) dissolved in saline 3 days/week for 4 weeks then administrated orally with OP (40 mg/kg body weight) dissolved in corn oil 3 days/week for another 4 weeks. The results obtained showed that OP-exposed rats had significant increase in serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, lactate dehydrogenase, bilirubin, serum and liver tumor necrosis factor-α, interleukin-1β and malondialdehyde, serum interleukin-6 and interleukin-10 and significant decrease in serum alkaline phosphatase, acid phosphatase, serum and liver superoxide dismutase, glutathione peroxidase, and catalase. OP caused an inhibitory action on the gene expression of liver proteins. Rats treated with FA before OP exposure had near-normal values. In addition, FA prevented the degradation of liver deoxyribonucleic acid (DNA), and DNA reformation occurred. In conclusion, FA protects from dangerous OP-related hepatic effects, and these results were supported by molecular and histological investigations.