Cellgevity® supplement stalls diabetic renal dysfunction in male rats
Chronic excessive ROS formation instigates oxidative stress, inflammation and the inhibition of vital physiological processes, including renal Na+/K+-ATPase activity, thereby facilitating the progression of diabetic kidney damage. This study investigated the therapeutic impact of Cellgevity® (a poly-antioxidant supplement) against streptotozin-induced diabetic kidney dysfunction in male rats. Twenty-eight matured male rats randomised into – Control group, Diabetes-Untreated, Diabetes-Treated 1 and Diabetes-Treated 2 groups. Daily oral treatment of the Diabetes-Treated groups with therapeutic doses of Cellgevity® suspension in distilled water (25 mg/kg and 40 mg/kg BW respectively) was conducted for 30 days, while the control and Diabetic-Untreated groups received distilled water (placebo). Results show that Cellgevity® reduced kidney lipid peroxidation, prevented kidney enlargement and renal TNF-α and nitrite accumulation, and increased renal Na+/K+-ATPase activity compared to the untreated diabetic group. The Cellgevity® treatment also increased the actions of renal glutathione peroxidase, superoxide dismutase, and catalase by at least 70% compared to the untreated diabetic group. The serum levels of creatinine, blood urea nitrogen, HCO3, Na+ and K+ of the treated diabetic groups were also significantly normalised to the levels of the control group. The results demonstrate the anti-oxidative-nitrosative and anti-inflammation impact of Cellgevity® against diabetic renal dysfunction. The result presents a good incentive for anti-oxidant supplements in the management of diabetes and its complications.
Aderemi, A. S., Dare, O. O. and Akomaye, A. J. (2017). Modulating role of D-ribose-L-cysteine on oxidative stress in streptozotocin induced diabetes on plasma lipoprotein, oxidative status, spermatogenesis and steroidogenesis in male Wistar rats. Current Research in Diabetes & Obesity Journal, 9(2): 1–7.
Amponsah, S. K. N'Guessan, B.B., Akandawen, M., Aning, A., Agboli, S. Y., Danso, E.A., Opuni, K F.M., Asiedu-Gyekye, I. J. and Appiah-Opong, R., (2020). Effect of Cellgevity® supplement on selected rat liver cytochrome P450 enzyme activity and pharmacokinetic parameters of carbamazepine. Evidence-based Complementary and Alternative Medicine, 2020: 1-8.
Awodele, O. Badru, W. A., Busari, A. A., Kale, O. E., Ajayi, T. B., Udeh, R. O. and Emeka, P.M. (2018). Toxicological evaluation of therapeutic and supra-therapeutic doses of Cellgevity® on reproductive function and biochemical indices in Wistar rats. BMC Pharmacology and Toxicology, 19(1): 68-73.
Bohlender, J. M. Franke, S., Stein, G. and Wolf, G. (2005). Advanced glycation end products and the kidney. American Journal of Physiology-Renal Physiology, 289(4): F645–F659.
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72(1–2): 248–254.
Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414(6865): 813-20.
Coughlan, M. T., Coughlan, M. T. and Cooper, M. E. (2009). RAGE-Induced Cytosolic ROS Promote Mitochondrial Superoxide Generation in Diabetes. Journal of the American Society of Nephrology, 20(4): 742–752.
Djemli-Shipkolye, A., Coste, T., Raccah, D., Vague, P., Pieroni, G. and Gerbi, A., (2001). Na+/K+-ATPase alterations in diabetic rats: relationship with lipid metabolism and nerve physiological parameters. Cellular and Molecular Biology.7(2): 297–304.
Dufayet De La Tour, D. Vague, P., Coste, T., Moriscot, C., Jannot, M. F. and Raccah, D. (1998). Erythrocyte Na/K ATPase activity and diabetes: relationship with C-peptide level. Diabetologia. 41(9): 1080–1084.
Ebaid, H., Bashandy, S., Abdel-Mageed, A. M., Al-Tamimi, J., Hassan, I. and Alhazza, I. M. (2020). Folic acid and melatonin mitigate diabetic nephropathy in rats via inhibition of oxidative stress. Nutrition and Metabolism, 17, 6. https://doi.org/10.1186/s12986-019-0419-7
Febiyanto, N. Yamazaki, C., Kameo, S., Sari, D. K., Puspitasari, I.M., Sunjaya, D. K., Herawati, D M. D., Nugraha, G. I., Fukuda, T. and Koyama, H. (2017). Effects of selenium supplementation on the diabetic condition depend on the baseline selenium status in KKAy Mice. Biological Trace Element Research, 181(1): 71–81.
Forbes, J. M., Coughlan, M. T. and Cooper, M. E. (2008). Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes, 57(6): 1446–1454.
Fujita, H., Fujishima, H., Chida, S., Takahashi, K., Qi, Z., Kanetsuna, Y., Breyer, M.D., Harris, R.C., Yamada, Y. and Takahashi, T. (2009). Reduction of renal superoxide dismutase in progressive diabetic nephropathy. Journal of the American Society of Nephrology, 20(6): 1303–1313.
Galle, J. (2001). Oxidative stress in chronic renal failure. Nephrology Dialysis Transplantation, 16(11): 2135–2137.
Golbidi, S., Badran, M. and Laher, I. (2011). Diabetes and alpha lipoic acid. Frontiers in Pharmacology, 2: 1-15
Guide for the Care and Use of Laboratory Animals (1996). Guide for the Care and Use of Laboratory Animals. National Academies Press. https://doi.org/10.17226/5140
Ha, H. and Lee, H. B. (2001). Oxidative stress in diabetic nephropathy: basic and clinical information. Current Diabetes Reports, 1(3): 282–287.
Hadwan, M. H. (2018). Simple spectrophotometric assay for measuring catalase activity in biological tissues. BMC Biochemistry, 19(1),7. https://doi.org/10.1186/s12858-018-0097-5
Faselis, C., Katsimardou, A., Imprialos, K., Deligkaris, P., Kallistratos, M. and Dimitriadis, K. (2020). Microvascular complications of type 2 diabetes mellitus. Current Vascular Pharmacology, 18(2), 117–124. https://doi.org/10.2174/1570161117666190502103733
Iannello, S., Milazzo, P. and Belfiore, F. (2007). Animal and human tissue Na+/K+-ATPase in obesity and diabetes: A new proposed enzyme regulation. American Journal of the Medical Sciences, 333(1): 1–9.
Ismail-Beigi, F. and Edelman, I. S. (1971). The mechanism of the calorigenic action of thyroid hormone: Stimulation of Na+ + K+-activated adenosinetriphosphatase activity. Journal of General Physiology, 57(6): 710–722.
Iwalokun, B. A. and Iwalokun, S. O. (2007). Association between erythrocyte Na+K+-ATPase activity and some blood lipids in type 1 diabetic patients from Lagos, Nigeria. BMC Endocrine Disorders, 7(1): 1–8.
Kaplan, J. (2002). Biochemistry of Na,K-ATPase. Annual Review of Biochemistry, 71: 511–535.
Kashihara, N., Haruna, Y.K., Kondeti, V.S. and Kanwar, Y. (2010). Oxidative stress in diabetic nephropathy. Current Medicinal Chemistry, 17(34): 4256–4269.
Kataya, H. H., Hamza, A.A., Ramadan, G.A., Khasawneh, M. A., (2011). Effect of licorice extract on the complications of diabetes nephropathy in rats. Drug and Chemical Toxicology, 34(2): 101–108.
Koc, B., Erten, V., Yilmaz, M. I., Sonmez, A. and Kocar, I. H., (2003). The relationship between red blood cell Na/K-ATPase activities and diabetic complications in patients with type 2 diabetes mellitus. Endocrine. 21(3): 273–278.
Konrad, R. J., Mikolaenko, I., Tolar, J. F., Liu, K. and Kudlow, J. E., (2001). The potential mechanism of the diabetooenic action of streptozotocin: Inhibition of pancreatic β-cell O-GlcNAc-selective N-acetyl-β-D-glucosaminidase. Biochemical Journal, 356(1): 31–41.
Kuhad, A. and Chopra, K. (2007). Curcumin attenuates diabetic encephalopathy in rats: Behavioral and biochemical evidences. European Journal of Pharmacology, 576(1–3): 34–42.
Kuhad, A. and Chopra, K. (2008). Effect of sesamol on diabetes-associated cognitive decline in rats. Experimental Brain Research. 185(3): 411–420.
Lash, L. H. (2015). Mitochondrial glutathione in diabetic nephropathy. Journal of Clinical Medicine, 4(7): 14-28.
Lee, M., Cho, S., Roh, K., Chae, J.Park, J. H., Park, J., Lee, M. A., Kim, J., Auh, C. K., Yeom, C.H. and Lee, S., (2017) Glutathione alleviated peripheral neuropathy in oxaliplatin-treated mice by removing aluminum from dorsal root ganglia. American Journal of Translational Research, 9(3): 926–939.
Lim, A. K. and Tesch, G. H. (2012). Inflammation in diabetic nephropathy. Mediators of inflammation, 2012, 146154. https://doi.org/10.1155/2012/146154
Lutchmansingh, F. K., Hsu, J. W., Bennett, F. I., Badaloo, A. V., McFarlane-Anderson, N., Gordon-Strachan, G. M., Wright-Pascoe, R. A., Jahoor, F. and Boyne, M. S. (2018). Glutathione metabolism in type 2 diabetes and its relationship with microvascular complications and glycemia. PloS one, 13(6) e0198626.
Mason, S. A., Keske, M. A. and Wadley, G. D. (2021). Effects of vitamin C supplementation on glycemic control and cardiovascular risk factors in people with type 2 diabetes: A GRADE-Assessed systematic review and meta-analysis of randomized controlled trials. Diabetes Care. 44(2): 618–630.
Misra, H. P. and Fridovich, I. (1972) ‘The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological Chemistry, 247(10): 3170–3175.
Navarro, J. F. and Mora, C. (2005) Role of inflammation in diabetic complications. Nephrology Dialysis Transplantation. 20(12): 2601–2604,
Ogunlabi, O. O., Adegbesan, B. O., Ezima E.N., Adebisi, A, A. (2021). Cellgevity® attenuates liver distruption, oxidative stress and inflammation in STZ-diabetic male rats. Scientific African, 14: https://doi.org/10.1016/j.sciaf.2021.e0105
Ohkawa, H., Ohishi, N. and Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2): 351–358.
Palsamy, P. and Subramanian, S. (2011). Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2-Keap1 signaling. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1812(7): 719–731.
Rotruck, J. T. Pope, A. L., Ganther, H. E., Swanson, A. B., Hafeman, D. G., Hoekstra, W. G., (1973). Selenium: Biochemical role as a component of glutathione peroxidase. Science, 179(4073): 588–590.
Santuré, M., Pitre, M., Marette, A., Deshaies, Y., Lemieux, C., Larivière, R., Nadeau, A., Bachelard, H. (2002) ‘Induction of insulin resistance by high-sucrose feeding does not raise mean arterial blood pressure but impairs haemodynamic responses to insulin in rats’, British Journal of Pharmacology. 137(2): 185–196.
Sekhar, R. V. (2011). Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care, 34(1): 162–167.
Singh, D. K., Winocour, P. and Farrington, K. (2011). Oxidative stress in early diabetic nephropathy: Fueling the fire. Nature Reviews Endocrinology, 7(3): 176-84.
Szkudelski, T. and Szkudelska, K. (2011) ‘Anti-diabetic effects of resveratrol’, Annals of the New York Academy of Sciences. 1215(1): 34–39.
Tiwari, B. K., Pandey, K. B., Abidi, A. B. and Rizvi, S. I. (2013). Markers of oxidative stress during diabetes mellitus. Journal of Biomarkers, 2013, 378790: 1-8.
Ueno, Y., Kizaki, M., Nakagiri, R., Kamiya, T., Sumi, H., Osawa, T., (2002). Dietary glutathione protects rats from diabetic nephropathy and neuropathy. Journal of Nutrition, 132(5): 897–900.
Vague, P., Coste, T. C., Jannot, M. F., Raccah, D. and Tsimaratos, M. (2004). C-peptide, Na+,K+-ATPase, and diabetes. Experimental Diabesity Research, 5: 37–50.
Yang, D. K. and Kang, H.-S. (2018). Anti-diabetic effect of cotreatment with quercetin and resveratrol in streptozotocin-induced diabetic rats. Biomolecules & Therapeutics, 26(2): 130-138.
Zadhoush, F., Sadeghi, M. and Pourfarzam, M. (2015). Biochemical changes in blood of type 2 diabetes with and without metabolic syndrome and their association with metabolic syndrome components. Journal of Research in Medical Sciences, 20(8): 763–770.
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