Characteristic of Streptozotocin-Nicotinamide-Induced Inflammation in A Rat Model of Diabetes-Associated Renal Injury

Authors

  • Heru Sasongko Doctoral Program, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia; Department of Pharmacy, Universitas Sebelas Maret, Surakarta, Indonesia https://orcid.org/0000-0003-2787-1837
  • Arief Nurrochmad Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Abdul Rohman Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia; Center of Excellence, Institute for Halal Industry and Systems, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Agung Endro Nugroho Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.9460

Keywords:

Diabetes mellitus, Inflammation, Nicotinamide, Streptozotocin

Abstract

Background: Chemical agents such as streptozotocin (STZ) and nicotinamide (NAD) are used in animal models of diabetes mellitus and their related consequences in the kidneys. Several studies have been conducted to determine the modeling, however, the results are still unclear. Moreover, diabetic nephropathy is considered to begin with an inflammatory reaction in the kidneys. 

Objectives: This study aims to investigate the metabolic profile STZ and NAD induce inflammation in the kidney. 

Methods: The male Wistar rats used were divided into control and STZ-induced diabetes. Half of the diabetes group received a single dose of nicotinamide (230 mg/Kg) 15 minutes after STZ injection and all groups were monitored for 6 weeks. Furthermore, the profiles of creatinine, urea, and uric acid from serum and urine were observed and the kidney inflammation was tested by immunohistochemistry (IHC) with IL-6 and TNF-α parameters. 

Results: The result shows that the administration of a single dose of 230 mg/kg NAD in diabetic rats induced with 50 mg/kg and 65 mg/kg STZ affects body weight and kidney organ index. For 6 weeks of testing, both doses of STZ were enhanced several parameters of kidney damage in diabetic rats in blood and urine chemical parameters. Furthermore, the use of NAD to promote inflammation in STZ-induced diabetic rats gave no significant difference. However, NAD can help mice live longer and avoid problems throughout the test. 

Conclusions: The use of NAD leads to inflammation in Streptozotocin-induced diabetic rats. Therefore, the administration of Nicotinamide is recommended since it helps the rats live longer during the experiment. 

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References

Sasongko H, Lestari RG, Yugatama A, Farida Y, Sugiyarto S. Antidiabetic and antioxidant effect combination Vasconcellea pubescens A.DC. and Momordica charantia L. extract in alloxan induced diabetic rats. Pharmacogn J. 2020;12(2):311-5. DOI: https://doi.org/10.5530/pj.2020.12.49

Khan NU, Lin J, Liu X, Li H, Lu W, Zhong Z, et al. Insights into predicting diabetic nephropathy using urinary biomarkers. Biochim Biophys Acta. 2020;1868(10):140475. https://doi.org/10.1016/j.bbapap.2020.140475 PMid:32574766 DOI: https://doi.org/10.1016/j.bbapap.2020.140475

Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271-81. https://doi.org/10.1016/j.diabres.2018.02.023 PMid:29496507 DOI: https://doi.org/10.1016/j.diabres.2018.02.023

Kishore L, Kaur N, Singh R. Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocin-nicotinamide induced diabetic nephropathy. J Food Drug Anal. 2017;25(3):576-88. https://doi.org/10.1016/j.jfda.2016.08.009 PMid:28911644 DOI: https://doi.org/10.1016/j.jfda.2016.08.009

Escott GM, da Silveira LG, da Cancelier VA, Dall’Agnol A, Silveiro SP. Monitoring and management of hyperglycemia in patients with advanced diabetic kidney disease. J Diabetes Complications. 2021;35(2):107774. https://doi.org/10.1016/j.jdiacomp.2020.107774 PMid:33168397 DOI: https://doi.org/10.1016/j.jdiacomp.2020.107774

Oguntibeju O. Pathophysiology and Complications of Diabetes Mellitus. London: InTech: BoD Books on Demand; 2012. p. 140. DOI: https://doi.org/10.5772/3460

Đorđević G, Rački S, Vujičić B, Turk T, Crnčević-Orlić Z. Pathophysiology and Complications of Diabetes Mellitus. London: InTech: 2012. p. 71.

Hu S, Wang J, Wang J, Li S, Jiang W, Liu Y. Renoprotective effect of fucoidan from Acaudina molpadioides in streptozotocin/ high fat diet-induced Type 2 diabetic mice. J Funct Foods. 2017;31:123-30. DOI: https://doi.org/10.1016/j.jff.2017.01.031

Jangale NM, Devarshi PP, Bansode SB, Kulkarni MJ, Harsulkar AM. Dietary flaxseed oil and fish oil ameliorates renal oxidative stress, protein glycation, and inflammation in streptozotocin-nicotinamide-induced diabetic rats. J Physiol Biochem. 2016;72(2):327-36. https://doi.org/10.1007/s13105-016-0482-8 PMid:27048415 DOI: https://doi.org/10.1007/s13105-016-0482-8

Ramzy MM, Essawy TA, Shamaa A, Mohamed SS. Evaluation of the effect of platelet rich plasma on wound healing in the tongue of normal and streptozotocin-induced diabetic albino rats: Histological, immunohistochemical, and ultrastructural study. Open Access Maced J Med Sci. 2020;8(A):666-89. DOI: https://doi.org/10.3889/oamjms.2020.5366

Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire- Buys D, et al. Experimental NIDDM: Development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes. 1998;47(2):224-9. https://doi.org/10.2337/diab.47.2.224 PMid:9519717 DOI: https://doi.org/10.2337/diabetes.47.2.224

Hidayat AF, Chan CK, Mohamad J, Kadir HA. Leptospermum flavescens Sm. protect pancreatic β cell function from streptozotocin involving apoptosis and autophagy signaling pathway in in vitro and in vivo case study. J Ethnopharmacol. 2018;226:120-31. https://doi.org/10.1016/j.jep.2018.08.020 PMid:30118836 DOI: https://doi.org/10.1016/j.jep.2018.08.020

Cruz PL, Moraes-Silva IC, Ribeiro AA, Machi JF, de Melo MD, dos Santos F, et al. Nicotinamide attenuates streptozotocin-induced diabetes complications and increases survival rate in rats: Role of autonomic nervous system. BMC Endocr Disord. 2021;21(1):133. https://doi.org/10.1186/s12902-021-00795-6 PMid:34182970 DOI: https://doi.org/10.1186/s12902-021-00795-6

Hu Y, Wang Y, Wang L, Zhang H, Zhang H, Zhao B, et al. Effects of nicotinamide on prevention and treatment of streptozotocin-induced diabetes mellitus in rats. Chin Med J (Engl). 1996;109(11):819-22. PMid:9275363

Melo SS, Arantes MR, Meirelles MS, Jordão AA Jr., Vannucchi H. Lipid peroxidation in nicotinamide-deficient and nicotinamide-supplemented rats with streptozotocin-induced diabetes. Acta Diabetol. 2000;37(1):33-9. https://doi.org/10.1007/s005920070033 PMid:10928234 DOI: https://doi.org/10.1007/s005920070033

Szkudelski T. Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp Biol Med (Maywood). 2012;237(5):481-90. https://doi.org/10.1258/ebm.2012.011372 PMid:22619373 DOI: https://doi.org/10.1258/ebm.2012.011372

Donate-Correa J, Luis-Rodríguez D, Martín-Núñez E, Tagua VG, Hernández-Carballo C, Ferri C, et al. Inflammatory targets in diabetic nephropathy. J Clin Med. 2020;9(2):458. https://doi.org/10.3390/jcm9020458 PMid:32046074 DOI: https://doi.org/10.3390/jcm9020458

Guo L, Jiang B, Li D, Xiao X. Nephroprotective effect of adropinin against streptozotocin-induced diabetic nephropathy in rats: Inflammatory mechanism and YAP/TAZ factor. Drug Des Dev Ther. 2021;15:589-600. https://doi.org/10.2147/DDDT.S294009 PMid:33623368 DOI: https://doi.org/10.2147/DDDT.S294009

Omoboyowa DA, Karigidi KO, Aribigbola TC. Nephro-protective efficacy of Blighia sapida stem bark ether fractions on experimentally induced diabetes nephropathy. Comp Clin Pathol. 2021:30(1):25-33. DOI: https://doi.org/10.1007/s00580-020-03186-w

Elangovan A, Subramanian A, Durairaj S, Ramachandran J, Lakshmanan DK, Ravichandran G, et al. Antidiabetic and hypolipidemic efficacy of skin and seed extracts of Momordica cymbalaria on alloxan induced diabetic model in rats. J Ethnopharmacol. 2019;241:111989. https://doi.org/10.1016/j.jep.2019.111989 PMid:31150795 DOI: https://doi.org/10.1016/j.jep.2019.111989

Khan HA, Ibrahim KE, Khan A, Alrokayan SH, Alhomida AS. Immunostaining of proinflammatory cytokines in renal cortex and medulla of rats exposed to gold nanoparticles. Histol Histopathol. 2017;32(6):597-607. https://doi.org/10.14670/HH-11-825 PMid:27678417

Lenzen S. The mechanisms of alloxan-and streptozotocin-induced diabetes. Diabetologia. 2008;51(2):216-26. https://doi.org/10.1007/s00125-007-0886-7 PMid:18087688 DOI: https://doi.org/10.1007/s00125-007-0886-7

Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50(6):537-46. PMid:11829314

Dwitiyanti D, Rachmania RA, Efendi K, Septiani R, Jihadudin P. In vivo activities and in silico study of jackfruit seeds (Artocarpus heterophyllus Lam.) on the reduction of blood sugar levels of gestational diabetes rate induced by streptozotocin. Open Access Maced J Med Sci. 2019;7(22):3819-26. https://doi.org/10.3889/oamjms.2019.512 PMid:32127984 DOI: https://doi.org/10.3889/oamjms.2019.512

Iwansyah AC, Luthfiyanti R, Ardiansyah RC, Rahman N, Andriana Y, Hamid HA. Antidiabetic activity of Physalis angulata L. fruit juice on streptozotocin-induced diabetic rats. S Afr J Bot. 2021. https://doi.org/10.1016/j.sajb.2021.08.045 DOI: https://doi.org/10.1016/j.sajb.2021.08.045

Domingueti CP, Dusse LM, das Carvalho MG, de Sousa LP, Gomes KB, Fernandes AP. Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. J Diabetes Complications 2016;30(4):738-45. https://doi.org/10.1016/j.jdiacomp.2015.12.018 PMid:26781070 DOI: https://doi.org/10.1016/j.jdiacomp.2015.12.018

Haneda M, Koya D, Isono M, Kikkawa R. Overview of glucose signaling in mesangial cells in diabetic nephropathy. J Am Soc Nephrol. 2003;14(5):1374-82. https://doi.org/10.1097/01.asn.0000064500.89551.76 PMid:12707407 DOI: https://doi.org/10.1097/01.ASN.0000064500.89551.76

Cordero-Pérez P, Sánchez-Martínez C, García-Hernández PA, Saucedo AL. Metabolomics of the diabetic nephropathy: Behind the fingerprint of development and progression indicators. Nefrología (Engl Ed). 2020;40(6):585-96. https://doi.org/10.1016/j.nefro.2020.07.002 PMid:33036786 DOI: https://doi.org/10.1016/j.nefroe.2020.12.002

Gosmanov AR, Wall BM, Gosmanova EO. Diagnosis and treatment of diabetic kidney disease. Am J Med Sci. 2014;347(5):406-13. https://doi.org/10.1097/MAJ.0000000000000185 PMid:24553399 DOI: https://doi.org/10.1097/MAJ.0000000000000185

Elmarakby AA, Sullivan JC. Relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy. Cardiovasc Ther. 2012;30(1):49-59. https://doi.org/10.1111/j.1755-5922.2010.00218.x PMid:20718759 DOI: https://doi.org/10.1111/j.1755-5922.2010.00218.x

Mima A. Inflammation and oxidative stress in diabetic nephropathy: New insights on its inhibition as new therapeutic targets. J Diabetes Res. 2013;2013:248563. https://doi.org/10.1155/2013/248563 PMid:23862164 DOI: https://doi.org/10.1155/2013/248563

Wong C, Ho A, Tong P, Yeung C, Kong A, Lun S, et al. Aberrant activation profile of cytokines and mitogen‐activated protein kinases in Type 2 diabetic patients with nephropathy. Clin Exp Immunol. 2007;149(1):123-31. https://doi.org/10.1111/j.1365-2249.2007.03389.x PMid:17425653 DOI: https://doi.org/10.1111/j.1365-2249.2007.03389.x

Moresco RN, Sangoi MB, De Carvalho JA, Tatsch E, Bochi GV. Diabetic nephropathy: Traditional to proteomic markers. Clin Chim Acta. 2013;421:17-30. https://doi.org/10.1016/j.cca.2013.02.019 PMid:23485645 DOI: https://doi.org/10.1016/j.cca.2013.02.019

Ortiz A, Egido J. Is there a role for specific anti-TNF strategies in glomerular diseases? Nephrol Dial Transplant. 1995;10(3):309-11.

Dömling A, Li X. TNF-α: The shape of small molecules to come? Drug Discov Today. 2022;27(1):3-7. https://doi.org/10.1016/j.drudis.2021.06.018 PMid:34229081 DOI: https://doi.org/10.1016/j.drudis.2021.06.018

Navarro JF, Mora-Fernández C. The role of TNF-α in diabetic nephropathy: Pathogenic and therapeutic implications. Cytokine Growth Factor Rev. 2006;17(6):441-50. https://doi.org/10.1016/j.cytogfr.2006.09.011 PMid:17113815 DOI: https://doi.org/10.1016/j.cytogfr.2006.09.011

Misseri R, Meldrum D, Dinarello C, Dagher P, Hile K, Rink R, et al. TNF-α mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling. Am J Physiol Renal Physiol. 2005;288(2):F406-11. https://doi.org/10.1152/ajprenal.00099.2004 PMid:15507546 DOI: https://doi.org/10.1152/ajprenal.00099.2004

Su H, Lei CT, Zhang C. Interleukin-6 signaling pathway and its role in kidney disease: An update. Front Immunol. 2017;8:405. https://doi.org/10.3389/fimmu.2017.00405 PMid:28484449 DOI: https://doi.org/10.3389/fimmu.2017.00405

Araújo LS, Torquato BG, da Silva CA, dos Reis Monteiro ML, dos Santos Martins ALM, da Silva MV, et al. Renal expression of cytokines and chemokines in diabetic nephropathy. BMC Nephrol. 2020;21(1):308. https://doi.org/10.1186/s12882-020-01960-0 PMid:32723296 DOI: https://doi.org/10.1186/s12882-020-01960-0

Singla K, Singh R. Nephroprotective effect of Curculigo orchiodies in streptozotocin-nicotinamide induced diabetic nephropathy in wistar rats. J Ayurveda Integr Med. 2020;11(4):399-404. https://doi.org/10.1016/j.jaim.2020.05.006 PMid:32782114 DOI: https://doi.org/10.1016/j.jaim.2020.05.006

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Published

2022-01-03

How to Cite

1.
Sasongko H, Nurrochmad A, Rohman A, Nugroho AE. Characteristic of Streptozotocin-Nicotinamide-Induced Inflammation in A Rat Model of Diabetes-Associated Renal Injury. Open Access Maced J Med Sci [Internet]. 2022 Jan. 3 [cited 2024 Nov. 21];10(T8):16-22. Available from: https://oamjms.eu/index.php/mjms/article/view/9460