The Effects of Ghrelin on Renal Complications in Newborn Diabetic Rats

Year 2020, Volume: 79 Issue: 1, 1 - 6, 17.06.2020

Ayse Karatug Kacar Ozlem Sacan Neslihan Ozıclı Sehnaz Bolkent Refiye Yanardag Sema Bolkent

https://doi.org/10.26650/EurJBiol.2020.0043

Abstract

Objective: Ghrelin is an orexigenic hormone mainly released from the stomachs of rats and takes a significant part in the development of newborn rats. Ghrelin has been shown to possess antioxidant, anti-apoptotic, and anti-inflammatory properties. In this study, we aimed to examine microscopical and biochemical parameters in the kidney of newborn nontreated diabetic and ghrelin-treated diabetic rats. Materials and Methods: Wistar-type newborn rats were divided into four groups. First group: control rats given physiological saline for four weeks; second group: control animals given ghrelin from the third day to the fourth week; third group: diabetic rats given streptozotocin (STZ) on the second day after birth as a single dose; fourth group: diabetic rats given ghrelin from the third day to the fourth week. Results: There was no microscopic difference between the kidney tissues of non-treated diabetic and ghrelin-treated diabetic rats. Lipid peroxidation levels decreased, while superoxide dismutase, catalase activities, and glutathione levels increased in the diabetic group given ghrelin. Serum urea, uric acid, creatinine levels, myeloperoxidase, and xanthine oxidase activities decreased in diabetic rats treated with ghrelin. Conclusion: It can be said that the ghrelin given exogenously has a protective effect in some degree on renal complications in newborn diabetic rats.

Keywords

Diabetes, ghrelin, kidney

Supporting Institution

This work was supported by Scientific Research Project Coordination Unit of Istanbul University.

Project Number

BYP-36942

References

• 1. Edlund H. Developmental biology of the pancreas. Diabetes 2001; 50(Suppl 1): S5-S9.
• 2. Brissova M, Fowler MJ, Nicholson WE, Chu A, Hirshberg B, Harlan DM, et al. Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy. J Histochem Cytochem 2005; 53: 1087-97.
• 3. Cabrera O, Berman DM, Kenyon NS, Ricordi C, Berggren PO, Caicedo A. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci USA 2006; 103: 2334-9.
• 4. Wierup N, Svensson H, Mulder H, Sundler F. The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regul Pept 2002; 107: 63-9.
• 5. Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L. Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. Proc Natl Acad Sci USA 2004; 101: 2924-9.
• 6. Chanoine JP, Wong AC. Ghrelin gene expression is markedly higher in foetal pancreas compared with foetal stomach: effect of maternal fasting. Endocrinology 2004; 145: 3813-20.
• 7. O. Ukkola, Ghrelin and metabolic disorders. Curr Protein Pept Sc 2009; 10-1: 2-7.
• 8. Ostergard T, Hansen TK, Nyholm B, Gravholt CH, Djurhuus CB, Hosoda H, et al. Circulating ghrelin concentrations are reduced in healthy offspring of type 2 diabetic subjects, and are increased in women independent of a family history of type 2 diabetes. Diabetologia 2003; 46-1: 134-6.
• 9. Poykko SM, Kellokoski E, Horkkoe S, Kauma H, Kesäniemi YA, Ukkola O. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 2003;52-10: 2546-53.
• 10. Barazzoni R, Zanetti M, Ferreira C, Vinci P, Pirulli A, Mucci M, et al. Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome. J Clin Endocrinol Metab 2007; 92: 3935-40.
• 11. McCowen KC, Maykel JA, Bistrian BR, Ling PR. Circulating ghrelin concentrations are lowered by intravenous glucose or hyperinsulinemic euglycemic conditions in rodents. J Endocrinol 2002; 175: R7-R11.
• 12. Saad MF, Bernaba B, Hwu CM, Jinagouda S, Fahmi S, Kogosov E, et al. Insulin regulates plasma ghrelin concentration. J Clin Endocrinol Metab 2002; 87: 3997-4000.
• 13. Broglio F, Arvat E, Benso A, Gottero C, Muccioli G, Papotti M, et al. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 2001; 86: 5083-6.
• 14. Broglio F, Gottero C, Prodam F, Gauna C, Muccioli G, Papotti M, et al. Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab 2004; 89: 3062-5.
• 15. Nasri H, eian-Kopaei MR. Protective effects of herbal antioxidants on diabetic kidney disease. J Res Med Sci 2014; 82-3.
• 16. Cooper ME. Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet 1998; 352: 213-9.
• 17. Winegrad AI. Banting lecture 1986. Does a common mechanism induce the diverse complications of diabetes? Diabetes 1987; 36(3): 396-406.
• 18. Baynes, J.W. Role of oxidative stress in development of complications in diabetes. Diabetes 1991; 40: 405-12.
• 19. Freeman BA, Crapo JD. Biology of disease: free radicals and tissue injury. Lab Invest 1982; 47(5): 412-26.
• 20. Obay BD, Tasdemir E, Tumer C, Bilgin H, Atmaca M. Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model. Peptides 2008; 29: 448-55.
• 21. Zwirska-Korczala K, Adamczyk-Sowa M, Sowa P, Pilc K, Suchanek R, Pierzchala K, et al. Role of leptin, ghrelin, angiotensin П and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism. J Physiol Pharmacol 2007; 58: 53-64.
• 22. Wiernsperger NF. Oxidative stress as a therapeutic target in diabetes: revisiting the controversy. Diabetes Metab 2003; 29: 579-85.
• 23. Maritim AC, Sanders RA, Watkins III JB. Diabetes, oxidative stress, and antioxidants:a review. J Biochem Mol Toxicol 2003; 17: 24-38.
• 24. Monnier L, Colette C, Mas E, Michel F, Cristol JP, Boegner C, et al. Regulation of oxidative stress by glycaemic control: evidence for an independent inhibitory effect of insulin therapy. Diabetologia 2009; 53: 562-71.
• 25. Aslam F, Iqbal S, Nasir M, Anjum AA. White sesame seed oil mitigates blood glucose level, reduces oxidative stress, and improves biomarkers of hepatic and renal function in participants with type 2 diabetes mellitus. J Am Coll Nutr 2018; 27: 1-12.
• 26. Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB. Ghrelin a hormone with multiple functions. Front Neuroendocrinol 2004; 25(1): 27-68.
• 27. Fujimura K, Wakino S, Minakuchi H, Hasegawa K, Hosoya K, Komatsu M et al. Ghrelin protects against renal damages induced by angiotensin-II via an antioxidative stress mechanism in mice. PLoS One 2014; 9(4): e94373.
• 28. Turk N, Dagistanli FK, Sacan O, Yanardag R, Bolkent S. Obestatin and insulin in pancreas of newborn diabetic rats treated with exogenous ghrelin. Acta Histochem 2012; 114(4): 349-57.
• 29. Bonsnes RW, Taussky HH. On the colorimetric determination of creatinine by the Jaffe reaction. J Biol Chem 1945; 158: 581-91.
• 30. Caraway WT. Determination of uric acid in serum by a carbonate method. Am J Clin Pathol 1955; 25(7): 840-5.
• 31. Barker SB. The direct colorimetric determination of urea in blood and urine. J Biol Chem 1944; 152: 453-63. 32. Beutler E. Glutathione in red cell metabolism. In: A Manual of Biochemical Methods. New York: Grune and Stratton 1975; pp. 112-4.
• 33. Ledwozyw A, Michalak J, Stepien A, Kadziołka A. The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis. Clin Chim Acta 1986; 155: 275-83.
• 34. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-6.
• 35. Mylorie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 1986; 82: 512-20.
• 36. Wei H, Frenkel K. In vivo formation of oxidized DNA bases in tumor promoter-treated mouse skin. Cancer Res 1991; 51(16): 4443-9.
• 37. Corte ED, Stirpe F. Regulation of xanthine oxidase in rat liver: Modifications of the enzyme activity of rat liver supernatant on storage at 20 degrees. Biochem J 1968; 108: 349-51.
• 38. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-75.
• 39. Brouwers B, Pruniau VP, Cauwelier EJ, Schuit F, Lerut E, Ectors N, et al. Phlorizin pretreatment reduces acute renal toxicity in a mouse model for diabetic nephropathy. J Biol Chem 2013; 288(38): 27200-7.
• 40. Koyuturk M, Sacan O, Karabulut S, Turk N, Bolkent S, Yanardag R, et al. The role of ghrelin on apoptosis, cell proliferation and oxidant-antioxidant system in the liver of neonatal diabetic rats. Cell Biol Int 2015; 39(7): 834-41.
• 41. Takeda R, Nishimatsu H, Suzuki E, Satonaka H, Nagata D, Oba S, et al. Ghrelin improves renal function in mice with ischemic acute renal failure. J Am Soc Nephrol 2006; 17(1): 113-21.
• 42. Nojiri T, Hosoda H, Kimura T, Tokudome T, Miura K, Takabatake H, et al. Protective effects of ghrelin on cisplatin-induced nephrotoxicity in mice. Peptides 2016; 82: 85-91. 43. Cuppage FE, Neagoy DR, Tate A. Repair of the nephron following temporary occlusion of the renal pedicle. Lab Invest 1967; 17: 66074.
• 44. Witzgall R, Brown D, Schwarz C, Bonventre JV. Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells. J Clin Invest 1994; 93: 2175-88.
• 45. Guo JK, Cantley LG. Cellular maintenance and repair of the kidney. Annu Rev Physiol 2010; 72: 357-76.
• 46. Danilewicz M, Wagrowska-Danilewicz M. Renal immunoexpression of ghrelin is attenuated in human proliferative glomerulopathies. Nefrologia 2010; 30(6): 633-8.
• 47. Li Y, Liu J, Liao G, Zhang J, Chen Y, Li L, et al. Early intervention with mesenchymal stem cells prevents nephropathy in diabetic rats by ameliorating the inflammatory microenvironment. Int J Mol Med 2018; 41(5): 2629-39.
• 48. Wang D, Zhang G, Chen X, Wei T, Liu C, Chen C, et al. Sitagliptin ameliorates diabetic nephropathy by blocking TGF-β1/Smad signaling pathway. Int J Mol Med 2018; 41(5): 2784-92.
• 49. van Ginhoven TM, Huisman TM, van den Berg JW, Ijzermans JN, Delhanty PJ, de Bruin RW. Preoperative fasting induced protection against renal ischemia/reperfusion injury is independent of ghrelin in mice. Nutr Res 2010; 30(12): 865-9.
• 50. Yaribeygi H, Mohammadi MT, Rezaee R, Sahebkar A. Fenofibrate improves renal function by amelioration of NOX-4, IL-18, and p53 expression in an experimental model of diabetic nephropathy. J Cell Biochem 2018; 119(9): 7458-69.
• 51. Neamati S, Alirezaei M, Kheradmand A. Ghrelin Acts as an Antioxidant Agent in the Rat Kidney. Int J Pept Res Ther 2011; 17-3: 23945.
• 52. Elsherbiny NM, Zaitone SA, Mohammad HMF, El-Sherbiny M. Renoprotective effect of nifuroxazide in diabetes-induced nephropathy: impact on NFjB, oxidative stress, and apoptosis. Toxicol Mech Method 2018; 28-6: 467-473.
• 53. Sudhakara G, Ramesh B, Mallaiah P. Sreenivasulu N, Saralakumari D. Protective effect of ethanolic extract of Commiphora mukul gum resin against oxidative stress in the brain of streptozotocin induced diabetic Wistar male rats. Excli J 2012; 11: 576-92.
• 54. Sacan O, Turkyilmaz IB, Bayrak BB, Mutlu O, Akev N, Yanardag R. Zinc supplementation ameliorates glycoprotein components and oxidative stress changes in the lung of streptozotocin diabetic rats. Biometals 2016; 29(2): 239-48.