Cinnamic acid abrogates bisphenol A-induced hepatotoxicity via suppression of pro-inflammatory cytokine and modulation of gene expressions of antioxidant enzymes in rats.

Bisphenol A (BPA) is regularly used to produce plastic products. Its hepatotoxicity has been unveiled. The effects of cinnamic acid on BPA exposure have not been comprehensively studied, and the key mechanism of action is yet to be unraveled. Rats were allocated into 5 groups. Group 1 (control) was given corn oil. Group 2 received BPA for 14 consecutive days. Group 3 received cinnamic acid at 50 mg/kg in co-administration with BPA while group 4 received cinnamic acid at 100 mg/kg, in co-administration with BPA. Cinnamic acid (CA) only (100 mg/kg) was given to group 5. BPA exposure significantly decreased catalase, glutathione-S-transferase, and superoxide dismutase activities and non-significantly diminished glutathione level. A reduction in the gene expression of catalase accompanied this. Our result showed significant gene elevation at the mRNA level of tumor necrosis factor-α and elevated malondialdehyde by BPA. The significantly elevated alanine transaminase and aspartate transaminase activities in addition to increased levels of total cholesterol, triglycerides, and very low-density lipoprotein with reduced high-density lipoprotein reflected the detrimental effect of BPA in the liver. Our results revealed that cinnamic acid could alleviate the increased pro-inflammatory cytokine level and oxidative stress by downregulating tumor necrosis factor-α gene. The histopathological evaluation confirmed the biochemical results. Hepatic alterations were ameliorated when cinnamic acid was co-administered with BPA. These findings suggest that downregulation of the TNF-α gene induced by cinnamic acid may participate in suppressing the BPA-induced oxidative stress. This offers a new idea to unmask the mechanism underlying cinnamic acid's interference with BPA-induced hepatic damage.