Abstract

PROTOCATECHUIC ACID AMELIORATES PARAQUAT-INDUCED HEPATIC AND PULMONARY TOXICITY IN RATS: DUAL NRF2 AND NF-KB MODULATORY ACTIVITY

Azza R Elkholy, Ahmed R. El-Sheakh and Ghada M. Suddek*

ABSTRACT

Background: Paraquat (PQ), a quarternary nitrogen herbicide, is a highly toxic compound for humans and animals and can cause severe injuries to many organs such as liver, lung and kidneys. The toxic effect of PQ is due to its ability to induce oxidative stress. The purpose of this research was to evaluate the effect of protocatchuic acid (PCA) on PQ-induced hepatic and pulmonary toxicity in rats. Methods: Male wistar rats were randomly divided into four groups, namely Control, PQ (15 mg/kg, i.p.) and PQ plus PCA (50 or 100 mg/kg, orally). At the end of the study, all rats were euthanized and then blood samples, liver and lungs were removed for further analysis. Results: PQ administration caused liver and lung toxicity as evidenced by elevated levels of ALT, AST, ALP, bilirubin and Y-GT and decreased serum albumin levels. A significant increase in total leukocytic count specifically lymphocytes was found in BALF from PQ-treated group. Moreover, both hepatic and pulmonary contents of MDA, TNF-α, NF-
KB, caspase-3 were significantly increased with a significant decrease in GSH, Nrf2 and LC3II contents. Exposure to PQ induced hepatic necrosis and neutrophilic infiltration into pulmonary tissues and congested blood vessels in the lungs. PCA protected both hepatic and pulmonary tissues against the oxidative damage caused by PQ injection. Significance: PCA could have anti-inflammatory, anti-oxidative and anti-apoptotic effects against PQ-induced hepatic and pulmonary toxicity.

Keywords: Protocatchuic acid; Paraquat; Apoptosis; Inflammation; Oxidative stress; NF-KB; Nrf2.