Protective role of protocatechuic acid in carbon tetrachloride-induced oxidative stress via modulation of proinflammatory cytokines levels in brain and liver of Wistar rats.

Protocatechuic acid (PCA) possesses numerous pharmacological activities, including antioxidative and anti-inflammatory activities. This study seeks to investigate its underlying mechanism of action in the liver and brain toxicity induced by CCl₄ in male albino rats. Rats were given PCA at 10 and 20 mg/kg daily and orally as a pretreatment for seven days. A single injection of CCl₄ was given 2 h later to induce brain and liver toxicity. CCl₄ moderately elevated the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). PCA lowered AST level significantly when compared to control. Total protein and albumin levels presented insignificant changes (p>0.05) in all groups while lipid profile showed increased total cholesterol level and reduced high-density lipoprotein (HDL) by CCl₄. PCA (10 mg/kg) significantly reduced the cholesterol level while the 20 mg/kg dose moderately prevented HDL reduction. There was an increased MDA production with a corresponding low GSH level in the group treated with CCl₄. Activities of superoxide dismutase, catalase, and glutathione-S-transferase in both organs also declined. PCA, especially at 10 mg/kg attenuated lipid peroxidation by increasing GSH level in the organs. Biochemical assays revealed the improvement of antioxidant enzyme activities by PCA in these organs. Furthermore, PCA lowered the level of proinflammatory cytokine COX 2 in the brain and liver while NF-kB expression was inhibited in the brain. Histopathology reports validated the effects of PCA. PCA exhibited protection against toxicity in these tissues through antioxidant and anti-inflammatory activities and the potential mechanism might be through modulation of the NF-κB/COX-2 pathway. [ABSTRACT FROM AUTHOR]