Fumaric Acid Protect the Cadmium-Induced Hepatotoxicity in Rats: Owing to Its Antioxidant, Anti-Inflammatory Action and Aid in Recast the Liver Function

In the modern world, indiscriminate human activities impelled environmental toxicity through heavy metals such as cadmium (Cd) that poses significant health hazards to the flora and fauna. Multiple mechanisms such as oxidative stress, inflammation, apoptotic cell death, and chromosomal aberrations underlie the Cd-induced organ toxicity with the liver and kidneys bearing most of the brunt. Fumaric acid (FA) is an organic acid (C₄H₄O₄) omnipresent in nature and attributed with such properties (e.g., antioxidant, anti-inflammatory, analgesic, chemopreventive, anti-psoriatic, immunomodulatory, and neuroprotective) that may bestow relief in Cd-induced liver damage. Hence, in the present study, the protective effects of FA were determined in Cd-induced hepatotoxicity in rats. Wistar rats were chronically exposed to Cd (5 mg/kg, p.o.) to induce liver dysfunction. The rats were subjected to FA (1.25, 2.5, 5 mg/kg; p.o.) pre-treatment for 28 days to observe effects on liver and serum biomarkers of oxidative stress, enzymatic activities, and hepatic damage (liver histopathology). Body weights, feed/water intake, body mass index (BMI), and non-invasive parameters (FIB-4 score; AST/ALT ratio) were quantified. Cd-triggered hepatic injury in rats through oxidative stress, derangement of hepatic serum biomarkers (ALT, AST, ALP, LDH, bilirubin, cholesterol, triglycerides, uric acid, and platelet count), and pathogenic alteration in non-invasive parameters. FA pre-treatment significantly protected rat livers against Cd toxicity by decreasing oxidative stress and improving the hepatic serum biomarkers and non-invasive parameters. In a histopathological analysis, FA prevented Cd-accrued hepatocellular damage. Fumaric acid showed potential to avert hepatic injury against cadmium in rats. Graphical abstract.

Keywords: Cadmium; Fumaric acid; Hepatotoxicity; Oxidative stress.