Agmatine ameliorates diabetes type 2-induced nephropathy in rats

Fatemah O. Kamel , Ohoud Shagroud , Mai A.Alim A.Sattar Ahmad , Gamal S Abd El-Aziz , Abdulhadi S. Burzangi , Duaa Bakhshwin , Maha Jamal , Shahid Karim

Asian Pacific Journal of Tropical Biomedicine ›› 2024, Vol. 14 ›› Issue (1) : 8 -16.

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Asian Pacific Journal of Tropical Biomedicine ›› 2024, Vol. 14 ›› Issue (1) :8 -16. DOI: 10.4103/2221-1691.393580
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Agmatine ameliorates diabetes type 2-induced nephropathy in rats
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Abstract

Objective: To assess the nephroprotective potential of agmatine in a rat model of streptozotocin-induced diabetic nephropathy. Methods: A single dose of streptozotocin (40 mg/kg) coupled with a fructose diet induced diabetes in Wistar rats. Agmatine (40 and 80 mg/kg) was administered to rats for 12 weeks. The body weight and fasting blood glucose were measured weekly. Insulin level, urine output, total protein, albumin, blood urea nitrogen, creatinine, and cystatin-C were also determined at the end of the experiment. Furthermore, superoxide dismutase, glutathione, interleukin-1β, interleukin-6, and tumor necrosis factor-alpha were evaluated in kidney tissue. Histopathological study was also performed using hematoxylin and eosin staining. Results: Agmatine at both doses significantly increased final body weight, and lowered fasting blood glucose, urine output, insulin, total protein, albumin, blood urea nitrogen, creatinine, and cystatin-C levels compared with the diabetic group (P < 0.05). Inflammatory markers and antioxidant effect were significantly improved in agmatine-treated rats. Moreover, the histopathological changes in renal structure were ameliorated by agmatine treatment. Conclusions: Agmatine alleviates diabetic nephropathy by improving renal functions and reducing inflammation and oxidative stress. The molecular mechanisms of its nephroprotective actions need to be investigated in future study.

Keywords

Agmatine / Type 2 diabetes / Nephropathy / Oxidative stress / Nephroprotection

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Fatemah O. Kamel, Ohoud Shagroud, Mai A.Alim A.Sattar Ahmad, Gamal S Abd El-Aziz, Abdulhadi S. Burzangi, Duaa Bakhshwin, Maha Jamal, Shahid Karim. Agmatine ameliorates diabetes type 2-induced nephropathy in rats. Asian Pacific Journal of Tropical Biomedicine, 2024, 14 (1) : 8-16 DOI:10.4103/2221-1691.393580

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Acknowledgments

The authors acknowledge the Deanship of Scientific Research at King Abdulaziz University, Jeddah, Saudi Arabia for the technical and financial support.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

The Deanship of Scientific Research at King Abdulaziz University, Jeddah, Saudi Arabia has funded this project, under grant no. (KEP MSc-42-140-1443).

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

Material preparation, data collection and analysis were performed by FOK, MAA and OS. Study design and conception were done by MAA, FOK, GSAE and SK. The first draft of the manuscript was written by ASB, OS and DB. The previous version and revised version of the manuscript was commented by MJ, SK and FOK. The final manuscript was read and approved by MAA, FOK, OS, ASB and SK.

References

[1]

Daryabor G, Atashzar MR, Kabelitz D, Meri S, Kalantar K. The effects of type 2 diabetes mellitus on organ metabolism and the immune system. Front Immunol 2020; 11. doi: 10.3389/fimmu.2020.01582.

[2]

Jager KJ, Kovesdy C, Langham R, Rosenberg M, Jha V, Zoccali C. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Kidney Int 2019; 96(5): 1048-1050.

[3]

Poloni JAT, Rotta LN. Diabetic kidney disease: Pathophysiological changes and urinalysis contribution to diagnosis-a narrative review. J Lab Precis Med 2022; 7: 3.

[4]

Grabias BM, Konstantopoulos K. The physical basis of renal fibrosis: Effects of altered hydrodynamic forces on kidney homeostasis. Am J Physiol Renal Physiol 2014; 306(5): F473-F485.

[5]

Kirkman MS, Mahmud H, Korytkowski MT. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes mellitus. Endocrinol Metab Clin North Am 2018; 47(1): 81-96.

[6]

Rossing P, Caramori ML, Chan JCN, Heerspink HJL, Hurst C, Khunti K, et al. KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int 2022; 102(5): S1-S127.

[7]

El-Kashef DH, El-Kenawi AE, Rahim MA, Suddek GM, Salem HA. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats. Can J Physiol Pharmacol 2016; 94(3): 278-286.

[8]

Kim JM, Lee JE, Cheon SY, Lee JH, Kim SY, Kam EH, et al. The anti-inflammatory effects of agmatine on transient focal cerebral ischemia in diabetic rats. J Neurosurg Anesthesiol 2016; 28(3): 203-213.

[9]

Piletz JE, Aricioglu F, Cheng JT, Fairbanks CA, Gilad VH, Haenisch B, et al. Agmatine: Clinical applications after 100 years in translation. Drug Discov Today 2013; 18(17-18): 880-893.

[10]

Lortie MJ, Novotny WF, Peterson OW, Vallon V, Malvey K, Mendonca M, et al. Agmatine, a bioactive metabolite of arginine. Production, degradation, and functional effects in the kidney of the rat. J Clin Invest 1996; 97(2): 413-420.

[11]

El-Kashef DH, El-Kenawi AE, Rahim MA, Suddek GM, Salem HA. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats. Can J Physiol Pharmacol 2016; 94(3): 278-286.

[12]

El-Sherbeeny NA, Nader MA, Attia GM, Ateyya H. Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways. Naunyn Schmiedebergs Arch Pharmacol 2016; 389(12): 1341-1351.

[13]

Miski SF, Ahmad MAAAS, Esmat A. Effect of agmatine on non-alcoholic fatty liver disease induced by type 2 diabetes in rats. J Pharm Res Int 2021; 33(31A): 127-134.

[14]

Breneman CB, Tucker L. Dietary fibre consumption and insulin resistance-the role of body fat and physical activity. Brit J Nutr 2013; 110(2): 375-383.

[15]

Oelke M, De Wachter S, Drake MJ, Giannantoni A, Kirby M, Orme S, et al. A practical approach to the management of nocturia. Int J Clin Pract 2017; 71(11): e13027.

[16]

Kennedy BW. Metabolic caging for animal research. Lab Anim (NY) 2012; 41(6): 171-176.

[17]

Hoogeveen EK. The epidemiology of diabetic kidney disease. Kidney Dial 2022; 2(3): 433-442.

[18]

Agarwal R. Pathogenesis of diabetic nephropathy. ADA Clinical Compendia 2021; 2021(1): 2-7.

[19]

Hojs R, Ekart R, Bevc S, Hojs N. Markers of inflammation and oxidative stress in the development and progression of renal disease in diabetic patients. Nephron 2016; 133(3): 159-162.

[20]

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.

[21]

Muskiet MHA, Smits MM, Morsink LM, Diamant M. The gut-renal axis: Do incretin-based agents confer renoprotection in diabetes? Nat Rev Nephrol 2014; 10(2): 88-103.

[22]

van Meer L, Moerland M, Cohen AF, Burggraaf J. Urinary kidney biomarkers for early detection of nephrotoxicity in clinical drug development. Br J Clin Pharmacol 2014; 77(6): 947-957.

[23]

Mestry SN, Dhodi JB, Kumbhar SB, Juvekar AR. Attenuation of diabetic nephropathy in streptozotocin-induced diabetic rats by Punica granatum Linn. leaves extract. J Tradit Complement Med 2017; 7(3): 273-280.

[24]

Shahin DHH, Sultana R, Farooq J, Taj T, Khaiser UF, Alanazi NSA, et al. Insights into the uses of traditional plants for diabetes nephropathy: A review. Curr Issues Mol Biol 2022; 44(7): 2887-2902.

[25]

Sun W, Liu X, Zhang H, Song Y, Li T, Liu X, et al. Epigallocatechin gallate upregulates NRF2 to prevent diabetic nephropathy via disabling KEAP1. Free Radic Biol Med 2017; 108: 840-857.

[26]

Alaofi AL. Sinapic acid ameliorates the progression of streptozotocin (STZ)-induced diabetic nephropathy in rats via NRF2/HO-1 mediated pathways. Front Pharmacol 2020; 11. doi: 10.3389/fphar.2020.01119.

[27]

Wu T, Ding L, Andoh V, Zhang J, Chen L. The mechanism of hyperglycemia-induced renal cell injury in diabetic nephropathy disease: An update. Life 2023; 13(2). doi: 10.3390/life13020539.

[28]

Qiu Y, Tang L. Roles of the NLRP3 inflammasome in the pathogenesis of diabetic nephropathy. Pharmacol Res 2016; 114: 251-264.

[29]

Kiritoshi S, Nishikawa T, Sonoda K, Kukidome D, Senokuchi T, Matsuo T, et al. Reactive oxygen species from mitochondria induce cyclooxygenase-2 gene expression in human mesangial cells. Diabetes 2003; 52(10): 2570-2577.

[30]

Forman HJ, Zhang H. Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy. Nat Rev Drug Discov 2021; 20(9): 689-709.

[31]

Mazumder PM, Rathinavelusamy P, Sasmal D. Role of antioxidants in phytomedicine with special reference to antidiabetic herbs. Asian Pac J Trop Dis 2012; 2: S969-S979.

[32]

Zhu X, Xu X, Du C, Su Y, Yin L, Tan X, et al. An examination of the protective effects and molecular mechanisms of curcumin, a polyphenol curcuminoid in diabetic nephropathy. Biomed Pharmacother 2022; 153. doi: 10.1016/j.biopha.2022.113438.

[33]

Ayinde KS, Olaoba OT, Ibrahim B, Lei D, Lu Q, Yin X, et al. AMPK allostery: A therapeutic target for the management/treatment of diabetic nephropathy. Life Sci 2020; 261. doi: 10.1016/j.lfs.2020.118455.

[34]

Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative stress: Harms and benefits for human health. Oxid Med Cell Longev 2017; 2017. doi: 10.1155/2017/8416763.

[35]

Hammad M, Raftari M, Cesário R, Salma R, Godoy P, Emami SN, et al. Roles of oxidative stress and Nrf2 signaling in pathogenic and non-pathogenic cells: A possible general mechanism of resistance to therapy. Antioxidants 2023; 12(7). doi: 10.3390/antiox12071371.

[36]

Ranasinghe R, Mathai M, Zulli A. Cytoprotective remedies for ameliorating nephrotoxicity induced by renal oxidative stress. Life Sci 2023; 318. doi: 10.1016/j.lfs.2023.121466.

[37]

Milosevic K, Stevanovic I, Bozic ID, Milosevic A, Janjic MM, Laketa D, et al. Agmatine mitigates inflammation-related oxidative stress in BV-2 cells by inducing a pre-adaptive response. Int J Mol Sci 2022; 23(7). doi: 10.3390/ijms23073561.

[38]

Navarro-González JF, Mora-Fernández C. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol 2008; 19(3): 433-442.

[39]

Sahakyan G, Vejux A, Sahakyan N. The role of oxidative stress-mediated inflammation in the development of T2DM-induced diabetic nephropathy: Possible preventive action of tannins and other oligomeric polyphenols. Molecules 2022; 27(24). doi: 10.3390/molecules27249035.

[40]

Yuan Q, Tang B, Zhang C. Signaling pathways of chronic kidney diseases, implications for therapeutics. Signal Transduct Target Ther 2022; 7(1): 182.

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