Fumaric acid protect the cadmium-induced hepatotoxicity in rats: owing to its antioxidant, anti-inflammatory action and
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ORIGINAL ARTICLE
Fumaric acid protect the cadmium-induced hepatotoxicity in rats: owing to its antioxidant, anti-inflammatory action and aid in recast the liver function Gurpreet Kaur 1 & Thippeswamy Boreddy Shivanandappa 2 & Manish Kumar 3 & Ajay Singh Kushwah 1 Received: 19 February 2020 / Accepted: 8 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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 Cdinduced 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. Keywords Cadmium . Fumaric acid . Hepatotoxicity . Oxidative stress
Introduction Cadmium (Cd) is a well-known category-I (International Agency for Research on Cancer) carcinogen, having potential Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01900-7) contains supplementary material, which is available to authorized users. * Ajay Singh Kushwah [email protected]; [email protected] 1
Department of Pharmacology, Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Bela, Ropar, Punjab 140111, India
2
Department of Biomedical Sciences, College of Pharmacy, Shaqra University, Al Dawadmi, Kingdom of Saudi Arabia
3
Department of Pharmacology, Swift School of Pharmacy, Ghaggar Sarai Rajpura, Patiala, Punjab 140401, India
to induce prostate, renal, breast, and pulmonary cancers. In
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