The Effects of Coenzyme Q10 on Inflammation Markers in Streptozotocin-Induced Diabetic Rats

Authors

  • Deniz Uluisik Department of Physiology, Faculty of Veterinary Medicine, University of Selcuk. Campus Konya, Turkey.
  • Ercan Keskin Department of Physiology, Faculty of Veterinary Medicine, University of Selcuk. Campus Konya, Turkey.

DOI:

https://doi.org/10.22456/1679-9216.80002

Keywords:

CoQ10, cytokine, diabetes, rats.

Abstract

Background: Coenzyme Q10 is a well-known cofactor in the mitochondrial electron transport chain required for ATP production. Coenzyme Q10 is recognized as an intracellular antioxidant that protects cell membrane phospholipids, mitochondrial membrane protein, and plasma low-density lipoprotein against oxidative damage caused by free radicals. Diabetes and its complications have been related to increased levels of free radicals and systemic proinflammatory cytokines and to an abnormal lipid profile. The aim of this study was to investigate the effects of coenzyme Q10 supplementation on some cytokine levels in streptozotocin-induced diabetic rats.

Materials, Methods & Results: In this study, 38 healthy, adult male rats were used. The rats were divided into 5 groups. All animals were housed in separated cages during the four weeks. The animals in group 1 was fed standard rat pellets for 4 weeks. It was administered at 0.3 mL corn oil intraperitoneally daily for four weeks in group 2 animals. The animals in group 3 was injected intraperitoneally with 10 mg/kg CoQ10 daily for 4 weeks. Group 4 was made diabetic by subcutaneous injections of streptozotocin at dose of 40 mg/kg in 0.1 M citrate buffer (pH 4.5) single daily dose for two days and group 5 was made diabetic by subcutaneous injections of streptozotocin at dose of 40 mg/kg in 0.1 M citrate buffer (pH 4.5) single daily dose for two days and then was injected intraperitoneally with 10 mg/kg CoQ10 daily for 4 weeks. During the experiment, three animals from group 4 and one animals from group 5 were died due to streptozotocin-induced hypoglycemia. At the end of the study, blood samples were taken from all animals. In these blood samples, IL-4, IL-6, IL-10 and TNF-α plasma levels were determined with ELISA using sandwich enzyme-linked immunosorbent method via commercial kits. In this study, IL-4 level as an anti-inflammatory cytokine significantly decreased (P < 0.05) with diabetes induction compared to control group level. IL-10 level in diabetic group was statistically different (P < 0.05) from control group level. CoQ10 application to diabetic animals improved the falling in IL-10 level of diabetic group (P < 0.05). IL-6 and TNF-α levels in diabetic group significantly increased (P < 0.05) in parallel with each other compared to control group levels. The same parameters were reduced (P < 0.05) by CoQ10 application in diabetic animals.

Discussion: In this study, the occurred changes in pro- and anti-inflammatory cytokines with experimentally induced diabetes are expected results and these results are consistent with some studies related diabetes. These results may be considered to hazardous effects and inflammation caused by diabetes on liver, pancreas and other tissues. CoQ10 suppressed the increments in plasma pro-inflammatory cytokine levels, whereas it restored the reducing in anti-inflammatory cytokine levels arising due to diabetes. The obtained results from this study after CoQ10 application supported similar studies used CoQ10 application against deleterious effects of diabetes in animals and humans. Therefore, it is possible to say that CoQ10 may play important role in regulation of imbalance between inflammation markers in diabetes conditions and further studies are needed to clear the beneficial effects of CoQ10 treatment on the other inflammation markers in diabetes status.

Downloads

Download data is not yet available.

References

Abu-Hilal M., McPhail M.J., Marchand L. & Johnson C.D. 2006. Malondialdehyde and superoxide dismutase as potential markers of severity in acute pancreatitis. Journal of the Pancreas. 7(2): 185-192.

Ahmed H.H., Aly H.F. & Ali S.A. 2015. Potential impact of CoQ10 and vitamin E against (STZ) induced metabolic deterioration in the albino rats. International Journal of Pharmacy and Pharmaceutical Sciences. 7(11): 176-184.

Bach J.F. 1994. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocrine Reviews. 15(4): 516-542.

Bhagavan H.N. & Chopra R.K. 2007. Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations. Mitochondrion. 7: 78-88.

Crane F.L. 2001. Biochemical functions of coenzyme Q10. The Journal of the American College of Nutrition. 20(6): 591-598.

El-Abhar H.S. 2010. Coenzyme Q10: a novel gastroprotective effect via modulation of vascular permeability, prostaglandin E2, nitric oxide and redox status in indomethacin-induced gastric ulcer model. European Journal of Pharmacology. 649(1-3): 314-319.

El Morsy E.M., Kamel R. & Ahmed M.A. 2015. Attenuating effects of coenzyme Q10 and amlodipine in ulcerative colitis model in rats. Immunopharmacology and Immunotoxicology. 37(3): 244-251.

Fouad A.A., Al-Sultan A.I., Refaie S.M. & Yacoubi M.T. 2010. Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice. Toxicology. 274(1-3): 49-56.

Ihara Y., Toyokuni S., Uchida K., Odaka H., Tanaka T., Ikeda H., Hiai H., Seino Y. & Yamada Y. 1999. Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes. 48(4): 927-932.

Jin H.J., Xue Y., Chen G. & Wu Z.Y. 2013. Effect of coenzyme Q10 on the expression of tumor necrosis factor-α and interleukin-10 in gingival tissue of experimental periodontitis in rats. Zhonghua Kou Qiang Yi Xue Za Zhi. 48(11): 660-663.

Kallmann B.A., Hüther M., Tubes M., Feldkamp J., Bertrams J., Gries F.A., Lampeter E.F. & Kolb H. 1997. Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves’ disease. Diabetes. 46(2): 237-243.

Kandhare A.D., Ghosh P., Ghule A.E. & Bodhankar S.L. 2013. Elucidation of molecular mechanism involved in neuroprotective effect of Coenzyme Q10 in alcohol-induced neuropathic pain. Fundamental and Clinical Pharmacology. 27(6): 603-622.

Kim J.M. & Park E. 2010. Coenzyme Q10 attenuated DMH-induced precancerous lesions in SD rats. Journal of Nutritional Science and Vitaminology. 56(2): 139-144.

Ko K.S., Lee M., Koh J.J. & Kim S.W. 2001. Combined administration of plasmids encoding IL-4 and IL-10 prevents the development of autoimmune diabetes in non obese diabetic mice. Molecular Therapy. 4(4): 313-316.

Kucharska J., Braunova Z., Ulicna O., Zlatos L. & Gvozdjakova A. 2000. Deficit of coenzyme Q in heart and liver mitochondria of rats with streptozotocin-induced diabetes. Physiological Research. 49(4): 411-418.

Lee J., Hong Y.S., Jeong J.H., Yang E.J., Jhun J.Y., Park M.K., Jung Y.O., Min J.K., Kim H.Y., Park S.H. & Cho M.L. 2013. Coenzyme Q10 ameliorates pain and cartilage degradation in a rat model of osteoarthritis by regulating nitric oxide and inflammatory cytokines. Public Library of Science One. 8(7): e69362.

Lin Y., Berg A.H., Iyengar P., Lam T.K., Giacca A., Combs T.P., Rajala M.W., Du X., Rollman B., Li W., Hawkins M., Barzilai N., Rhodes C.J., Fantus I.G., Brownlee M. & Scherer P.E. 2005. The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species. The Journal of Biological Chemistry. 280(6): 4617-4626.

Mirmalek S.A., Gholamrezaei Boushehrinejad A., Yavari H., Kardeh B., Parsa Y., Salimi-Tabatabaee S.A., Yadollah-Damavandi S., Parsa T., Shahverdi E. & Jangholi E. 2016. Antioxidant and anti-inflammatory effects of Coenzyme Q10 on L-arginine-induced acute pancreatitis in rat. Oxidative Medicine and Cellular Longevity. 2016: 1-8. [http://dx.doi.org/10.1155/2016/5818479].

Olukman M., Sezer E.D., Ulker S., Sözmen E.Y. & Cınar G.M. 2010. Fenofibrate treatment enhances antioxidant status and attenuates endothelial dysfunction in streptozotocin-induced diabetic rats. Experimental Diabetes Research. 2010: 1-10. [http://dx.doi.org/10.1155/2010/828531].

Pennline K.J., Roque-Gaffney E. & Monahan M. 1994. Recombinant human IL-10 prevents the onset of diabetes in the non obese diabetic mouse. Clinical Immunology and Immunopathology. 71(2): 169-175.

Rabinovitch A. 1998. An update on cytokines in the pathogenesis of insulin-dependent diabetes mellitus. Diabetes/ Metabolism Reviews. 14(2): 129-151.

Rabinovitch A. & Skyler J.S. 1998. Prevention of type 1 diabetes. Medical Clinics of North America. 82(4): 739-755.

Rapoport M.J., Jaramillo A., Zipris D., Lazarus A.H., Serreze D.V., Leiter E.H., Cyopick P., Danska J.S. & Delovitch T.L. 1993. Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice. The Journal of Experimental Medicine. 178(1): 87-99.

Sanoobar M., Eghtesadi S., Azimi A., Khalili M., Khodadadi B., Jazayeri S., Gohari M.R. & Aryaeian N. 2015. Coenzyme Q10 supplementation ameliorates inflammatory markers in patients with multiple sclerosis: a double blind, placebo, controlled randomized clinical trial. Nutritional Neuroscience. 18(4): 169-176.

Schoenberg M.H., Büchler M., Gaspar M., Stinner A., Younes M., Melzner I., Bültmann B. & Beger H.G. 1990. Oxygen free radicals in acute pancreatitis of the rat. Gut. 31(10): 1138-1143.

Saxena M., Srivastava N. & Banerjee M. 2013. Association of IL-6, TNF-α and IL-10 gene polymorphisms with type 2 diabetes mellitus. Molecular Biology Reports. 40(11): 6271-6279.

Tran M.T., Mitchell T.M., Kennedy D.T. & Gilles J.T. 2001. Role of coenzyme Q10 in chronic heart failure, angina, and hypertension. Pharmacotherapy. 21(7): 797-806.

Van Exel E., Gussekloo J., de Craen A.J., Frölich M., Bootsma-Van Der Wiel A. & Westendorp R.G. 2002. Leiden 85 Plus Study. Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes: the Leiden 85-Plus Study. Diabetes. 51(4): 1088-1092.

Zheng X.X., Steele A.W., Hancock W.W., Stevens A.C., Nickerson P.W., Roy-Chaudhury P., Tian Y. & Strom T.B. 1997. A noncytolytic IL-10/Fc fusion protein prevents diabetes, blocks autoimmunity, and promotes suppressor phenomena in NOD mice. The Journal of Immunology. 158(9): 4507-4513.

Published

2017-01-01

How to Cite

Uluisik, D., & Keskin, E. (2017). The Effects of Coenzyme Q10 on Inflammation Markers in Streptozotocin-Induced Diabetic Rats. Acta Scientiae Veterinariae, 45(1), 5. https://doi.org/10.22456/1679-9216.80002

Issue

Section

Articles