The Effects of Conjugated Linoleic Acid and Berberine Supplementation on Markers of Allopurinol Activated Oxidative Stress in Broiler Chickens

Main Article Content

Vincent Dartigue Knox Van Dyke Hillar Klandorf Kimberly M. Barnes


Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid.  There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.

Article Details

How to Cite
DARTIGUE, Vincent et al. The Effects of Conjugated Linoleic Acid and Berberine Supplementation on Markers of Allopurinol Activated Oxidative Stress in Broiler Chickens. Medical Research Archives, [S.l.], v. 9, n. 10, oct. 2021. ISSN 2375-1924. Available at: <>. Date accessed: 29 nov. 2022. doi:
Research Articles


1. Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. Chronic inflammation and oxidative stress in human carcinogenesis. International Journal of Cancer. 2007 Dec 1;121(11):2381-6.
2. Cerutti P, Amstad P. Inflammation and oxidative stress in carcinogenesis. In Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation and Radiation Injury 1993 (pp. 387-390). Springer US.
3. Marku, L. and Klandorf, H. (2021). Plasma Urate and Neurodegenerative Disease. J. of Drug Design and Research 8(1):1078-1080.
4. Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ. Production of Reactive Oxygen Species by Mitochondria: CENTRAL ROLE OF COMPLEX III. Journal of Biological Chemistry 2003 September 19;278(38):36027-36031.
5. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 2009 Jan 1;417(1):1-13.
6. Martin KR, Barrett JC. Reactive oxygen species as double-edged swords in cellular processes: low-dose cell signaling versus high-dose toxicity. Hum Exp Toxicol 2002 02;21(2):71-75.
7. Wu W. The signaling mechanism of ROS in tumor progression. Cancer and Metastasis Reviews 2006;25(4):- 695-705.
8. D'Autreaux B&, Michel. ROS as signaling molecules: mechanisms that generate specificity in ROS homeostasis. Nature Reviews Molecular Cell Biology 2007;8(- 10):- 813.
9. Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 2015 6/5;97:55-74.
10. Cutler RG. Urate and ascorbate: their possible roles as antioxidants in determining longevity of mammalian species. Archives of gerontology and geriatrics. 1984 3(4):321-48.
11. Simoyi MF, Falkenstein E, Van Dyke K, Blemings KP, Klandorf H. Allantoin, the oxidation product of uric acid is present in chicken and turkey plasma. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology 2003;135(2):325-335.
12. Larson RA. The antioxidants of higher plants. Phytochemistry 1988;27(4):969-978.
13. Meeran SM, Katiyar S, Katiyar SK. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation. Toxicol Appl Pharmacol 2008 5/15;229(1):33-43.
14. Li Z, Geng Y, Jiang J, Kong W. Antioxidant and Anti-Inflammatory Activities of Berberine in the Treatment of Diabetes Mellitus. Evidence-Based Complementary and Alternative Medicine 2014;2014:12.
15. Liu S, Lee H, Hung C, Tsai C, Li T, Tang C. Berberine attenuates CCN2-induced IL-1β expression and prevents cartilage degradation in a rat model of osteoarthritis. Toxicol Appl Pharmacol 2015 11/15;289(1):20-29.
16. Xie J, Xu Y, Huang X, Chen Y, Fu J, Xi M, et al. Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway. Tumor Biol 2015;36(2):1279-1288.
17. Teulier L, Rouanet J, Letexier D, Romestaing C, Belouze M, Rey B, et al. Cold-acclimation-induced non-shivering thermogenesis in birds is associated with upregulation of avian UCP but not with innate uncoupling or altered ATP efficiency. J Exp Biol 2010 The Company of Biologists Ltd;213(14):2476-2482
18. Abe T, Mujahid A, Sato K, Akiba Y, Toyomizu M. Possible role of avian uncoupling protein in down-regulating mitochondrial superoxide production in skeletal muscle of fasted chickens. FEBS Lett 2006 9/4;580(20):4815-4822.
19. Berardi M, Chou J. Fatty Acid Flippase Activity of UCP2 is Essential for Its Proton Transport in Mitochondria. Cell Metabolism 2014 9/2;20(3):541-552.
20. Mollica MP, Trinchese G, Cavaliere G, De Filippo C, Cocca E, Gaita M, et al. c9,t11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway. J Lipid Res 2014 May;55(5):837-849.
21. Viladomiu M, Hontecillas R, Bassaganya-Riera J. Modulation of inflammation and immunity by dietary conjugated linoleic acid. Eur J Pharmacol 2015.
22. Yang B, Chen H, Stanton C, Ross RP, Zhang H, Chen YQ, et al. Review of the roles of conjugated linoleic acid in health and disease. Journal of Functional Foods 2015;15:314-325.
23. Ramiah SK, Meng GY, Sheau Wei T, Swee Keong Y, Ebrahimi M. Dietary Conjugated Linoleic Acid Supplementation Leads to Downregulation of PPAR Transcription in Broiler Chickens and Reduction of Adipocyte Cellularity. PPAR Res 2014;2014:137652.
24. Klandorf H, Rathore DS, Iqbal M, Shi X, Van Dyke K. Accelerated tissue aging and increased oxidative stress in broiler chickens fed allopurinol. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 2001 6;129(2):93-104.
25. Settle T, Carro MD, Falkenstein E, Radke W, Klandorf H. The effects of allopurinol, uric acid, and inosine administration on xanthine oxidoreductase activity and uric acid concentrations in broilers. Poultry Science 2012 November 01;91(11):2895-2903.
26. Settle T, Falkenstein E, Klandorf H. The effect of allopurinol administration on mitochondrial respiration and gene expression of xanthine oxidoreductase, inducible nitric oxide synthase, and inflammatory cytokines in selected tissues of broiler chickens. Poultry Science 2015 October 01;94(10):2555-256.
27. Hall SB, Khudaish EA, Hart AL. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part 1. An adsorption-controlled mechanism. Electrochim Acta 1998;43(5–6):579-588.
28. Barnes KM, Winslow NR, Shelton AG, Hlusko KC, Azain MJ. Effect of dietary conjugated linoleic acid on marbling and intramuscular adipocytes in pork. Journal of Animal Science. 2012 Apr 1;90(4):1142-9.
29. Van Dyke K, Castranova V. Cellular chemiluminescence. CRC; 1987 Jul 1.
30. Kong LD, Yang C, Ge F, Wang HD, Guo YS. A Chinese herbal medicine Ermiao wan reduces serum uric acid level and inhibits liver xanthine dehydrogenase and xanthine oxidase in mice. Journal of Ethnopharmacology. 2004 Aug 31;93(2):325-30.
31. Takahashi Y, Kushiro M, Shinohara K, Ide T. Dietary conjugated linoleic acid reduces body fat mass and affects gene expression of proteins regulating energy metabolism in mice. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology 2002;133(3):395-404.
32. Xing L, Zhang L, Liu T, Hua Y, Zheng P, Ji G. Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver. Eur J Pharmacol 2011;668(3):467-471.
33. Cantwell H, Devery R, O'shea M, Stanton C. The effect of conjugated linoleic acid on the antioxidant enzyme defense system in rat hepatocytes. Lipids. 1999 Aug 1;34(8):833-9.
34. Halliwell B. Antioxidants in human health and disease. Annu Rev Nutr 1996;16(1):33-50.
35. Greenhalgh SN, Thompson AI, Henderson NC, Iredale JP. Oxidative Stress and Liver Inflammation. Studies on Hepatic Disorders: Springer; 2015. p. 123-147.
36. Hwang J, Wang C, Chou F, Tseng T, Hsieh Y, Lin W, et al. Inhibitory effect of berberine on tert-butyl hydroperoxide-induced oxidative damage in rat liver. Arch Toxicol 2002;76(11):664-670.3