Cinnamic Acid through Reduction of Oxidative Injury and Modulation of Nrf2 Pathway Ameliorates Bisphenol A-induced Nephrotoxicity in Male Wistar Rats

Abstract

Bisphenol A is an environmental pollutant that induces oxidative stress in the kidney. Phytochemicals such ascinnamic acid have been demonstrated to possess antioxidative properties that could mitigate against oxidative stress.The current study investigates underlying pathways that may help elucidate the protective role of cinnamic acid (CA)against bisphenol A (BPA)-induced nephrotoxicity. Rats were divided randomly into five groups. Group 1 was thecontrol. Group 2 took BPA only. Group 3 was given BPA combined with CA (50 mg/kg), while group 4 had BPAand cinnamic acid (100 mg/kg). Group 5 received cinnamic acid only (100 mg/kg). Antioxidant parameters and proteinexpression levels were evaluated. Bisphenol A at 100 mg/kg significantly increased urea concentration and lipidperoxidation. Glutathione (GSH) level decreased, and superoxide dismutase (SOD), catalase, and glutathione-S-transferase (GST) presented lower activities than in the control (P>0.05). Cinnamic acid improved renal function bysignificantly reducing urea levels. Oxidative stress was reduced, as evidenced by lower malondialdehyde and higherantioxidant marker levels (GSH, SOD, catalase, and GST) compared with the BPA-administered group. qRT-PCRresults showed a decline in Nrf2 expression in BPA-treated rats compared with the control (P<0.05). However, thisdecline was reversed upon CA treatment. Cinnamic acid at 100 mg/kg to rats treated with bisphenol A preserved thestructural integrity of the kidney. The data obtained suggests that cinnamic acid’s protective effect against BPA-induced nephrotoxicity may be driven by its ability to decrease oxidative stress and reduce inflammation throughregulation of Nrf2 signaling pathway.