Hepatoprotective and Immunomodulatory Effects of Copper-nicotinate Complex Against Fatty Liver in Rat Model

Overview

Journal Vet World

Specialty Veterinary Medicine

Date 2020 Feb 26

PMID 32095039

Authors

Ahmed Medhat Hegazy

Ayman Samir Farid

Ahmed S Hafez

Rania M Eid

Soad M Nasr

Affiliations

Soon will be listed here.

Abstract

Aim: The current study was designed to evaluate the potential hepatoprotective and immunomodulatory effects of copper-nicotinate complex (CNC) against methionine- and choline-deficient diet (MCDD)-induced fatty liver in rats.

Materials And Methods: Forty male Wistar rats were randomly allocated into one of four equal-sized groups (G1-G4). The G1 group was fed a balanced diet and kept under normal conditions; the G2 group received CNC orally at a dose of 0.043 mg/kg body weight, 3 times/week for 4 weeks, and a balanced diet; the G3 group was fed an MCDD for 4 weeks; and the G4 group was fed an MCDD and administered CNC at the same dose and route as G2. Blood samples were collected for the determination of serum enzyme activity. After 4 weeks of treatment, liver specimens were collected for the evaluation of the oxidative/antioxidative markers, cytokine gene expression, and histopathological examination.

Results: CNC improved MCDD-induced liver dysfunctions by recovering serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities to their normal levels. The glutathione (GSH) level and superoxide dismutase (SOD) activity significantly decreased, while lipid peroxidation (as reflected by malondialdehyde [MDA]) markedly increased in the liver tissue of the MCDD group. After cotreatment with MCDD and CNC, the GSH level and SOD activity markedly increased and the MDA level significantly decreased to return to normal levels. After cotreatment with MCDD and CNC, significant downregulation of the mRNA expression of hepatic interleukin (IL)-1β, IL-4, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1 genes was found. Moreover, CNC reduced fatty liver complications by reducing the number of hepatic vacuolations, degenerative changes in the hepatocytes, and hemorrhage.

Conclusion: CNC has the potential to limit tissue injury and possibly prevent the progression to severe liver disease caused by an MCDD.

References

Salama R, Nassar A, Nafady A, Mohamed H . A novel therapeutic drug (copper nicotinic acid complex) for non-alcoholic fatty liver. Liver Int. 2007; 27(4):454-64. DOI: 10.1111/j.1478-3231.2007.01460.x. View

Dong H, Guo H, Liang Y, Wang X, Niu Y . Astragaloside IV synergizes with ferulic acid to suppress hepatic stellate cells activation in vitro. Free Radic Res. 2017; 51(2):167-178. DOI: 10.1080/10715762.2017.1290233. View

Deminice R, de Castro G, Francisco L, Silva L, Cardoso J, Frajacomo F . Creatine supplementation prevents fatty liver in rats fed choline-deficient diet: a burden of one-carbon and fatty acid metabolism. J Nutr Biochem. 2015; 26(4):391-7. DOI: 10.1016/j.jnutbio.2014.11.014. View

Noureddin M, Mato J, Lu S . Nonalcoholic fatty liver disease: update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine. Exp Biol Med (Maywood). 2015; 240(6):809-20. PMC: 4818965. DOI: 10.1177/1535370215579161. View

Jiang X, West A, Caudill M . Maternal choline supplementation: a nutritional approach for improving offspring health?. Trends Endocrinol Metab. 2014; 25(5):263-73. DOI: 10.1016/j.tem.2014.02.001. View

Sumida Y, Nakajima A, Itoh Y . Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014; 20(2):475-85. PMC: 3923022. DOI: 10.3748/wjg.v20.i2.475. View

Khoruts A, Stahnke L, McClain C, Logan G, Allen J . Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients. Hepatology. 1991; 13(2):267-76. View

Jiang Y, Beller D, Frendl G, Graves D . Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes. J Immunol. 1992; 148(8):2423-8. View

Milic S, Lulic D, Stimac D . Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations. World J Gastroenterol. 2014; 20(28):9330-7. PMC: 4110564. DOI: 10.3748/wjg.v20.i28.9330. View

10.

Pacana T, Cazanave S, Verdianelli A, Patel V, Min H, Mirshahi F . Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation in Diet-Induced Nonalcoholic Fatty Liver Disease. PLoS One. 2015; 10(8):e0136822. PMC: 4556375. DOI: 10.1371/journal.pone.0136822. View

11.

Lau J, Zhang X, Yu J . Animal models of non-alcoholic fatty liver disease: current perspectives and recent advances. J Pathol. 2016; 241(1):36-44. PMC: 5215469. DOI: 10.1002/path.4829. View

12.

Pawlak M, Lefebvre P, Staels B . Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J Hepatol. 2014; 62(3):720-33. DOI: 10.1016/j.jhep.2014.10.039. View

13.

Farid A, Hegazy A . Ameliorative effects of leaf extract on levofloxacin-induced hepatic toxicity in rats. Drug Chem Toxicol. 2019; 43(6):616-622. DOI: 10.1080/01480545.2019.1574811. View

14.

Feng W, Li Q, Wang W, Zhao T, Feng Y, Li F . Pharmacokinetics and bioavailability of chromium malate and its influence on trace metals absorption after oral or intravenous administration. Indian J Pharmacol. 2018; 50(2):75-83. PMC: 6044135. DOI: 10.4103/ijp.IJP_505_17. View

15.

Chen Q, Luo Z, Wu K, Huang C, Zhuo M, Song Y . Differential effects of dietary copper deficiency and excess on lipid metabolism in yellow catfish Pelteobagrus fulvidraco. Comp Biochem Physiol B Biochem Mol Biol. 2015; 184:19-28. DOI: 10.1016/j.cbpb.2015.02.004. View

16.

Farid A, Mido S, Linh B, Hayashi T, Horii Y . An atherogenic lipid profile with low serum paraoxonase-1 activity during nematode infection in rats. Eur J Clin Invest. 2010; 40(11):984-93. DOI: 10.1111/j.1365-2362.2010.02352.x. View

17.

Fisher N, Neil D, Williams A, Adams D . Serum concentrations and peripheral secretion of the beta chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1alpha in alcoholic liver disease. Gut. 1999; 45(3):416-20. PMC: 1727646. DOI: 10.1136/gut.45.3.416. View

18.

Ellman G . Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82(1):70-7. DOI: 10.1016/0003-9861(59)90090-6. View

19.

Stankovic M, Mladenovic D, Ninkovic M, Ethuricic I, Sobajic S, Jorgacevic B . The effects of α-lipoic acid on liver oxidative stress and free fatty acid composition in methionine-choline deficient diet-induced NAFLD. J Med Food. 2013; 17(2):254-61. PMC: 3929137. DOI: 10.1089/jmf.2013.0111. View

20.

Leifeld L, Dumoulin F, Purr I, Janberg K, Trautwein C, Wolff M . Early up-regulation of chemokine expression in fulminant hepatic failure. J Pathol. 2003; 199(3):335-44. DOI: 10.1002/path.1298. View