Protective role of butylated hydroxyanisole (BHA) and hydroxytoluene (BHT) against oxidative stress-induced inflammatory response in carbon tetrachloride-induced acute hepatorenal toxicity.

BACKGROUND: Any toxicity initially damages the hepatic system, followed by renal dysfunction. Previously, it was established that carbon tetrachloride (CCl4) intoxication severely damaged hepatocytes. Moreover, CCl4-mediated toxicity significantly impacted immune functions and influenced the inflammatory response, with mitochondrial dysfunction. The present study focused on the levels of inflammatory markers and mitochondrial dysfunction, as well as the protective role of BHA and BHT.

METHODS: In the present study, hepatorenal dysfunction was developed in experimental rats by applying a subcutaneous injection of CCl4 with a dose of 230 mg/kg bwt/rat/day. The level of immune toxicity was determined by measuring C-reactive protein (CRP), IL-6, 12, TNF-α, IL-10, and TGF-β in CCl4 intoxicated group and pretreated BHA and BHT groups. ROS generation and MMP were also measured in hepatic and renal cells using flow cytometric technique.

RESULTS: The level of toxicity was determined by a significant increase of CRP (407.29%), IL-6 (525.65%), IL-12 (1026.54%), and TNF-α (1007.33%) in CCl4 intoxicated group, while IL-10 and TGF-β were significantly decreased 84.65% and 66.36%, respectively. CCl4 intoxication caused decreased mitochondrial membrane potential and high levels of intracellular ROS generation. Pretreatment with BHA (0.5 mg/kg/bwt) and BHT (0.8 mg/kg/bwt) significantly (p<0.001, p<0.05) reduced inflammatory markers in the CCl4-treated group, restored mitochondrial membrane potential and decreased intracellular ROS levels.

CONCLUSION: BHA and BHT treatment could restrict the higher concentration of pro-inflammatory markers by scavenging ROS. Therefore, the study suggested that supplementation of BHA and BHT could be an alternative treatment for preventing hepatorenal dysfunctions.