Ameliorative effect of lycopene alone and in combination with co-enzyme Q10 in streptozotocin-induced diabetic nephropathy in experimental rats


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Authors

DOI:

https://doi.org/10.29228/ijpbp.24

Keywords:

Antioxidants, CoQ10, Diabetic nephropathy, Lycopene, Oxidative stress, Streptozotocin

Abstract

Diabetic nephropathy (DN) has become an utmost reason for long-standing renal dysfunction and end-stage renal disease globally. Oxidative stress induced by persistent hyperglycemia is considered a fundamental element in the evolution of DN. The goal of this research was to discover the outcome of appendages of natural antioxidants such as lycopene and co-enzyme Q10 (CoQ10) in DN rats and to observe the preventive effects in DN. A diabetes model was developed in a Wistar strain of male rats (200–250 g) by subcutaneous injection of streptozotocin (55 mg/kg). Development of nephropathy was assessed by renal function tests including blood glucose, creatinine, albumin, total protein, total bilirubin, uric acid, total cholesterol, triglycerides, and CRP level. Oxidative stress markers such as LPO and GSH content and activity of membrane-bound Na+/K+ ATPases were measured in kidney homogenate. Renal damage was assessed by performing a histopathological analysis. DN rats showed a significant elevation in creatinine, albumin, total protein, total bilirubin, uric acid, total cholesterol, triglycerides, CRP, and LPO levels whereas a significant reduction in creatinine clearance and GSH level. Treatment with antioxidants such as lycopene (5 mg/kg/p.o.) and CoQ10 (10 mg/kg/p.o.) along with their combination for 4 weeks notably altered the level of renal function biomarkers and oxidative stress markers. These antioxidants and their combination also protected the kidney from abnormal morphological changes. The present findings suggest that the combined administration of lycopene and CoQ10, which are antioxidants, exhibits synergistic effects in mitigating renal injury by reducing hyperglycemia, oxidative stress markers, and histopathological alterations.

References

Akbar, S., Bellary, S., & Griffiths, H. R. (2011). Dietary antioxidant interventions in type 2 diabetes patients: a meta-analysis. The British Journal of Diabetes & Vascular Disease, 11(2), 62-68.

Akinnuga, A. M., Bamidele, O., & Adewumi, A. J. (2019). Evaluation of kidney function parameters in diabetic rats following virgin coconut oil diet. Folia Medica, 61(2), 249-257.

Arora, A., Sairam, R., & Srivastava, G. (2002). Oxidative stress and antioxidative system in plants. Current Science, 82(10), 1227-1238.

Arora, M. K., & Singh, U. K. (2013). Molecular mechanisms in the pathogenesis of diabetic nephropathy: an update. Vascular Pharmacology, 58(4), 259-271.

Ashrafi, M., Nazifi, S., Namazi, F., Kazemipour, N., Karimi, B., Goudarzi, T., & Talebanzadeh, S. (2017). Renal protective effect of saffron aqueous extract in streptozotocin induced diabetic rats. International Journal of Medical Research and Health Sciences, 6, 151-161.

Balakumar, P., Arora, M. K., & Singh, M. (2009). Emerging role of PPAR ligands in the management of diabetic nephropathy. Pharmacological Research, 60(3), 170-173.

Bartoli, C. G., Buet, A., Gergoff Grozeff, G., Galatro, A., & Simontacchi, M. (2017). Ascorbate-glutathione cycle and abiotic stress tolerance in plants. In M. Hossain, S. Munné-Bosch, D. Burritt, P. Diaz-Vivancos, M. Fujita, & A. Lorence (Eds.), Ascorbic Acid in Plant Growth, Development and Stress Tolerance (pp. 177-200): Springer, Cham.

Bhattacharjee, N., Barma, S., Konwar, N., Dewanjee, S., & Manna, P. (2016). Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: an update. European Journal of Pharmacology, 791, 8-24.

Daniel, E., Mohammed, A., Tanko, Y., & Ahmed, A. (2015). Effects of lycopene on kidney antioxidant enzyme activities and functions in streptozotocin-induced diabetic Wistar rats. Cell Biology, 3(1), 1-13.

Elsayed, A., Elkomy, A., Elkammar, R., Youssef, G., Abdelhiee, E. Y., Abdo, W., Fadl, S. E., Soliman, A., & Aboubakr, M. (2021). Synergistic protective effects of lycopene and N-acetylcysteine against cisplatin-induced hepatorenal toxicity in rats. Scientific Reports, 11(1), 1-10.

Esu, K. D., Bakare, A. O., & Owoyele, B. V. (2022). Effects of co‐administration of vitamin E and lithium chloride on chronic constriction injury‐induced neuropathy in male Wistar rats: Focus on antioxidant and anti‐inflammatory mechanisms. Pain Practice, 22(2), 148-158.

Fakhruddin, S., Alanazi, W., & Jackson, K. E. (2017). Diabetes-induced reactive oxygen species: mechanism of their generation and role in renal injury. Journal of Diabetes Research, 2017, 8379327.

Forbes, J. M., Coughlan, M. T., & Cooper, M. E. (2008). Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes, 57(6), 1446-1454.

Fuller, B., Smith, D., Howerton, A., & Kern, D. (2006). Anti‐inflammatory effects of CoQ10 and colorless carotenoids. Journal of Cosmetic Dermatology, 5(1), 30-38.

Ghule, A. E., Jadhav, S. S., & Bodhankar, S. L. (2012). Trigonelline ameliorates diabetic hypertensive nephropathy by suppression of oxidative stress in kidney and reduction in renal cell apoptosis and fibrosis in streptozotocin induced neonatal diabetic (nSTZ) rats. International Immunopharmacology, 14(4), 740-748.

Gunasekera, R. S., Sewgobind, K., Desai, S., Dunn, L., Black, H. S., McKeehan, W. L., & Patil, B. (2007). Lycopene and lutein inhibit proliferation in rat prostate carcinoma cells. Nutrition and Cancer, 58(2), 171-177.

Hodgson, J., Watts, G., Playford, D., Burke, V., & Croft, K. (2002). Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. European Journal of Clinical Nutrition, 56(11), 1137-1142.

Horie, K., Miyata, T., Maeda, K., Miyata, S., Sugiyama, S., Sakai, H., De Strihou, C. V. Y., Monnier, V. M., Witztum, J. L., et al. (1997). Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy. The Journal of Clinical Investigation, 100(12), 2995-3004.

Ighodaro, O. M. (2018). Molecular pathways associated with oxidative stress in diabetes mellitus. Biomedicine & Pharmacotherapy, 108, 656-662.

Jain, M. D. (2015). Silibinin, a bioactive flavanone, prevents the progression of early diabetic nephropathy in experimental type‐2 diabetic rats. International Journal of Green Pharmacy, 9(2), 118-124.

Jain, P. G., Patil, D. J., Nayase, P., Surana, S. J., & Patil, P. P. (2020). Protective effect of diosgenin on streptozotocin induced diabetic nephropathy in experimental rats. International Journal of Pharmaceutical Sciences and Drug Research, 12(2), 201-207.

Kashihara, N., Haruna, Y., K Kondeti, V., & S Kanwar, Y. (2010). Oxidative stress in diabetic nephropathy. Current Medicinal Chemistry, 17(34), 4256-4269.

Kukner, A., Colakoglu, N., Ozogul, C., Naziroglu, M., & Firat, T. (2009). The effects of combined vitamin C and E in streptozotocin-induced diabetic rat kidney. Clinical Reviews and Opinions, 1(2), 29-36.

Lavender, S., Hilton, P., & Jones, N. (1969). The measurement of glomerular filtration-rate in renal disease. The Lancet, 294(7632), 1216-1219.

Lee, H. S., & Ku, S. K. (2008). Effect of Picrorrhiza rhizoma extracts on early diabetic nephropathy in streptozotocin-induced diabetic rats. Journal of Medicinal Food, 11(2), 294-301.

Leh, H. E., & Lee, L. K. (2022). Lycopene: A potent antioxidant for the amelioration of type II diabetes mellitus. Molecules, 27(7), 2335.

Li, X., Xiao, H., Lin, C., Sun, W., Wu, T., Wang, J., Chen, B., Chen, X., & Cheng, D. (2019). Synergistic effects of liposomes encapsulating atorvastatin calcium and curcumin and targeting dysfunctional endothelial cells in reducing atherosclerosis. International Journal of Nanomedicine, 14, 649-665.

Liu, W., Zhang, X., Liu, P., Shen, X., Lan, T., Li, W., Jiang, Q., Xie, X., & Huang, H. (2010). Effects of berberine on matrix accumulation and NF-kappa B signal pathway in alloxan-induced diabetic mice with renal injury. European Journal of Pharmacology, 638(1-3), 150-155.

Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193, 265-275.

Mahajan, M., Upasani, C., Upaganlawar, A., & Gulecha, V. (2020). Renoprotective effect of co-enzyme Q10 and N-acetylcysteine on streptozotocin-induced diabetic nephropathy in rats. International Journal of Diabetes and Clinical Research, 7(2), 1-12.

Mahmoodnia, L., Mohammadi, K., & Masumi, R. (2017). Ameliorative effect of lycopene effect on cisplatin-induced nephropathy in patient. Journal of Nephropathology, 6(3), 144-149.

Marcovecchio, M. L., Lucantoni, M., & Chiarelli, F. (2011). Role of chronic and acute hyperglycemia in the development of diabetes complications. Diabetes Technology & Therapeutics, 13(3), 389-394.

Mogensen, C. E. (2004). Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas. In C. E. Mogensen (Ed.), The Kidney and Hypertension in Diabetes Mellitus (pp. 905-960): CRC Press.

Moron, M. S., Depierre, J. W., & Mannervik, B. (1979). Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochimica et Biophysica Acta (BBA)-General Subjects, 582(1), 67-78.

Nakagawa, T., Yokozawa, T., Yamabe, N., Goto, H., Shibahara, N., Rhyn, D. Y., & Shimada, Y. (2005). Long‐term treatment with Hachimi‐jio‐gan attenuates kidney damage in spontaneously diabetic WBN/Kob rats. Journal of Pharmacy and Pharmacology, 57(9), 1205-1212.

Orhan, N., Aslan, M., Orhan, D. D., Ergun, F., & Yeşilada, E. (2006). In-vivo assessment of antidiabetic and antioxidant activities of grapevine leaves (Vitis vinifera) in diabetic rats. Journal of Ethnopharmacology, 108(2), 280-286.

Pansare, K., Upasani, C., Upaganlwar, A., Sonawane, G., & Patil, C. (2021). Pre-clinical study of lycopene alone and in combination with olive oil in streptozotocin-induced diabetic nephropathy. Vidyabharati International Interdisciplinary Research Journal, 5(Special Issue on International Virtual Conference on Innovation in Multidisciplinary Studies-IVCIMS 2021), 320-332.

Parohan, M., Sarraf, P., Javanbakht, M. H., Foroushani, A. R., Ranji-Burachaloo, S., & Djalali, M. (2021). The synergistic effects of nano-curcumin and coenzyme Q10 supplementation in migraine prophylaxis: A randomized, placebo-controlled, double-blind trial. Nutritional Neuroscience, 24(4), 317-326.

Patel, A. N., Bandawane, D. D., & Mhetre, N. K. (2014). Pomegranate (Punica granatum Linn.) leaves attenuate disturbed glucose homeostasis and hyperglycemia mediated hyperlipidemia and oxidative stress in streptozotocin induced diabetic rats. European Journal of Integrative Medicine, 6(3), 307-321.

Platé, M., Guillotin, D., & Chambers, R. C. (2020). The promise of mTOR as a therapeutic target pathway in idiopathic pulmonary fibrosis. European Respiratory Review, 29, 200269.

Puah, B. P., Jalil, J., Attiq, A., & Kamisah, Y. (2021). New insights into molecular mechanism behind anti-cancer activities of lycopene. Molecules, 26(13), 3888.

Raghunathan, S., Tank, P., Bhadada, S., & Patel, B. (2014). Evaluation of buspirone on streptozotocin induced type 1 diabetes and its associated complications. BioMed Research International, 2014, 948427.

Ritz, E. (2013). Clinical manifestations and natural history of diabetic kidney disease. Medical Clinics, 97(1), 19-29.

Ritz, E., Zeng, X. X., & Rychlík, I. (2011). Clinical manifestation and natural history of diabetic nephropathy. Diabetes and the Kidney, 170, 19-27.

Rojas-Rivera, J., Ortiz, A., & Egido, J. (2012). Antioxidants in kidney diseases: the impact of bardoxolone methyl. International Journal of Nephrology, 2012, 321714.

Rosenfeldt, F. L., Haas, S. J., Krum, H., Hadj, A., Ng, K., Leong, J. Y., & Watts, G. F. (2007). Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. Journal of Human Hypertension, 21(4), 297-306.

Sangar, C., & Singh, J. (2016). Effects of Streptozotocin-induced Type I Diabetes Mellitus on Cation contents in Urinary Bladder tissues of the rat. International Journal of Pharmaceutical Sciences and Research, 7(2), 789-797.

Sayahi, M., & Shirali, S. (2017). The antidiabetic and antioxidant effects of carotenoids: a review. Asian Journal of Pharmaceutical Research and Health Care, 9(4), 186-191.

Schena, F. P., & Gesualdo, L. (2005). Pathogenetic mechanisms of diabetic nephropathy. Journal of the American Society of Nephrology, 16(3), S30-S33.

Senthil, S., Sridevi, M., & Pugalendi, K. (2007). Cardioprotective effect of oleanolic acid on isoproterenol-induced myocardial ischemia in rats. Toxicologic Pathology, 35(3), 418-423.

Sharma, P., Jha, A. B., Dubey, R. S., & Pessarakli, M. (2012). Reactive oxygen species, oxidative damage, and antioxidative defense mechanism in plants under stressful conditions. Journal of Botany, 2012, 217037.

Shi, J., Kakuda, Y., & Yeung, D. (2004). Antioxidative properties of lycopene and other carotenoids from tomatoes: synergistic effects. Biofactors, 21(1-4), 203-210.

Slater, T., & Sawyer, B. (1971). The stimulatory effects of carbon tetrachloride and other halogenoalkanes on peroxidative reactions in rat liver fractions in vitro. General features of the systems used. Biochemical Journal, 123(5), 805-814.

Sudamrao Garud, M., & Anant Kulkarni, Y. (2014). Hyperglycemia to nephropathy via transforming growth factor beta. Current Diabetes Reviews, 10(3), 182-189.

Suvarchala Reddy, V. N., Ganga Raju, M., Alekhya, B., & Subrahmanyam, C. (2019). Attenuation of Diabetic Nephropathy In Streptozotocin Induced Diabetic Rats By Methanolic Extract Of Bougainvillea Spectabilis Aerial Parts. International Journal of Pharmaceutical Sciences and Drug Research, 11(1), 16-21.

Tavafi, M. (2013). Diabetic nephropathy and antioxidants. Journal of Nephropathology, 2(1), 20-27.

Teoh, S., Latiff, A. A., & Das, S. (2010). Histological changes in the kidneys of experimental diabetic rats fed with Momordica charantia (bitter gourd) extract. Romanian Journal of Morphology and Embryology, 51(1), 91-95.

Upaganlawar, A., & Gandhi, H. (2010). Effect of vitamin E alone and in combination with lycopene on biochemical and histopathological alterations in isoproterenol-induced myocardial infarction in rats. Journal of Pharmacology and Pharmacotherapeutics, 1(1), 24-31.

Vetvicka, V., & Vetvickova, J. (2018). Combination therapy with glucan and coenzyme Q10 in murine experimental autoimmune disease and cancer. Anticancer Research, 38(6), 3291-3297.

Wang, G. G., Lu, X. H., Li, W., Zhao, X., & Zhang, C. (2011). Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats. Evidence-Based Complementary and Alternative Medicine, 2011, 323171.

Wang, S., Yang, Z., Xiong, F., Chen, C., Chao, X., Huang, J., & Huang, H. (2016). Betulinic acid ameliorates experimental diabetic-induced renal inflammation and fibrosis via inhibiting the activation of NF-κB signaling pathway. Molecular and Cellular Endocrinology, 434, 135-143.

Yokozawa, T., Nakagawa, T., Oya, T., Okubo, T., & Juneja, L. R. (2005). Green tea polyphenols and dietary fibre protect against kidney damage in rats with diabetic nephropathy. Journal of Pharmacy and Pharmacology, 57(6), 773-780.

Zhu, J., Wang, C. G., & Xu, Y. G. (2011). Lycopene attenuates endothelial dysfunction in streptozotocin-induced diabetic rats by reducing oxidative stress. Pharmaceutical Biology, 49(11), 1144-1149.

Zhu, R., Chen, B., Bai, Y., Miao, T., Rui, L., Zhang, H., Xia, B., Li, Y., Gao, S., et al. (2020). Lycopene in protection against obesity and diabetes: A mechanistic review. Pharmacological Research, 159, 104966.

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Published

15.06.2023

How to Cite

Rasal, P. B., Kasar, G. N., Mahajan, M. S., Upaganlawar, A. B., & Upasani, C. D. (2023). Ameliorative effect of lycopene alone and in combination with co-enzyme Q10 in streptozotocin-induced diabetic nephropathy in experimental rats. International Journal of Plant Based Pharmaceuticals, 3(1), 123–130. https://doi.org/10.29228/ijpbp.24

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Research Articles
Received 2023-04-18
Accepted 2023-06-14
Published 2023-06-15