Hydrogen-Rich Water Ameliorates Pancreatic Cell Necrosis and Regulates Cytokine Levels in Streptozotocin-Induced Diabetic Rats doi.org/10.26538/tjnpr/v5i8.6

Main Article Content

Budi Susatia
Ekowati Retnaningtyas
Siti N. Arifah
Sri R. Lestari

Abstract

Water plays an important role in the metabolic processes. An unhealthy lifestyle leads to an increase in free radicals, which causes type 2 diabetes mellitus (T2DM). Hydrogen-rich water (HW) is water with dissolved hydrogen gas and has been implicated to have antioxidant activity. This study was aimed at analyzing the effect of HW on pancreatic cell necrosis and cytokine level in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were fed a high-fat diet (HFD) for four weeks before being injected intraperitoneally with low dose STZ (35 mg/kg bw) to obtain DM rats. Blood glucose values of >200 mL/dL were considered diabetic rats. The experimental rats were randomly divided into five groups: healthy (normal rats without STZ injection), DM, DM + metformin (45 mg/kg bw), DM + HW, and DM + HW + metformin. The treatments were administered orally for fourteen days. After that, the rats were dissected using Ket-A-Xyl; serum and liver samples were obtained to determine the concentrations of IL-10 and IL-1β. The pancreas was collected and examined for cell damage, while histology of the Islet of Langerhans was analyzed descriptively. The results showed that HW reduced blood glucose levels, body weight, and IL-1β concentration, increased IL-10 concentration, and improvednecrotic cells of the pancreas in comparison to DM rats. HW could be one of the therapies for T2DM patients by lowering glucose levels, regulating cytokine levels, and repairing β-cells in the pancreas.

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How to Cite
Susatia, B., Retnaningtyas, E., N. Arifah, S., & R. Lestari, S. (2021). Hydrogen-Rich Water Ameliorates Pancreatic Cell Necrosis and Regulates Cytokine Levels in Streptozotocin-Induced Diabetic Rats: doi.org/10.26538/tjnpr/v5i8.6. Tropical Journal of Natural Product Research (TJNPR), 5(8), 1360–1364. Retrieved from https://tjnpr.org/index.php/home/article/view/439
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References

El-Sharkawy AM, Sahota O, Lobo DN. Acute and chronic effects of hydration status on health. Nutr Rev. 2015; 73(2):97-109.

Goodman AB. Behaviors and Attitudes Associated with Low Drinking Water Intake Among US Adults, Food Attitudes and Behaviors Survey, 2007. Prev Chronic Dis. 2013; 10(4):120248-120259.

Madjd A, Taylor MA, Delavari A, Malekzadeh R, Macdonald IA, Farshchi HR. Beneficial effects of replacing diet beverages with water on type 2 diabetic obese women following a hypoenergetic diet: A randomized, 24-week clinical trial. Diabetes Obes Metab. 2017; 19(1):125-132.

Madjd A, Taylor MA, Delavari A, Malekzadeh R, Macdonald IA, Farshchi HR. Effects on weight loss in adults of replacing diet beverages with water during a hypoenergetic diet: a randomized, 24-wk clinical trial. Am J Clin Nutr. 2015; 102(6):1305-1312.

Naumann J, Biehler D, Lüty T, Sadaghiani C. Prevention and Therapy of Type 2 Diabetes—What Is the Potential of Daily Water Intake and Its Mineral Nutrients? Nutr. 2017; 9(8):914-931.

Elikee ER, Ezugwu CO, Ihekwereme CP, Nzekwe IT, Ajaghaku DL. Co-administration Effects of Newbouldia laevis (P. Beauv.) Leaves and Garcinia kola (Heckel) Seed Extracts on Animal Models of Hepatotoxicity and Diabetes. Trop J Nat Prod Res. 2021; 5(2):389-396.

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D, Williams R. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019; 157 (2019):107843-107851.

International Diabetes Federation (IDF). IDF Diabetes Atlas: 9th Edition [Online]. 2019. Available from: https://www.idf.org/aboutdiabetes/what-is-diabetes/factsfigures.htmL

World Health Organization. Diabetes [Online]. 2020. Available from:https://www.who.int/news-room/fact-sheets/detail/diabetes

Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes – Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. 2020; 10(1):107-111.

Al-Goblan AS, Al-Alfi MA, Khan MZ. Mechanism linking diabetes mellitus and obesity. Diabetes Metab Syndr Obes Targets Ther. 2014; 7(2014):587-591.

Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present and future. Lancet. 2014; 383(9922):1068-1083.

Skyler JS, Bakris GL, Bonifacio E, Darsow T, Eckel RH, Groop L, Groop PH, Handelsman Y, Insel RA, Mathieu C, McElvaine AT, Palmer JP, Pugliese A, Scharz DA, Sosenko JM, Wilding JPH, and Ratner RE. Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis. Diabetes. 2017; 66(2):241-255.

Gofur A, Witjoro A, Ningtiyas EW, Setyowati E, Mukharromah SA, Athoillah MF, Lestari SR. The Evaluation of Dietary Black Soybean and Purple Sweet Potato on Insulin Sensitivity in Streptozotocin - Induced Diabetic Rats. Pharmacogn J. 2019; 11(4):639-646.

Tsalamandris S, Antonopoulos AS, Oikonomou E, Papamikroulis G-A, Vogiatzi G, Papaioannou S, Deftereos S, and Tousoulis D. The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives. Eur Cardiol Rev. 2019; 14(1):50-59.

Kartika R, Purnamasari D, Pradipta S, Larasati RA, Wibowo H. Impact of Low Interferon-γ and IL-10 Levels on TNF-α and IL-6 Production by PHA-Induced PBMCs in Type 2 Diabetes Mellitus. J Inflamm Res. 2020; 13(2020):187-193.

Atho’illah MF, Widyarti S, Rifa’i M. Elicited soybean (Glycine max L.) extract improves regulatory T cell activity in high fatfructose diet mice. In Malang, Indonesia: AIP Conference Proceedings; 2017. 1-6 p. [cited 2020 May 9]. Available from: http://aip.scitation.org/doi/abs/10.1063/1.4983415

Lestari SR, Atho’illah MF, Christina YI, Rifa’i M. Single garlic oil modulates T cells activation and proinflammatory cytokine in mice with high fat diet. J Ayurv Integr Med. 2020; 11(4):414-420.

Kamimura N, Nishimaki K, Ohsawa I, Ohta S. Molecular Hydrogen Improves Obesity and Diabetes by Inducing Hepatic FGF21 and Stimulating Energy Metabolism in db/db Mice. Obes. 2011; 19(7):1396-1403.

Amitani H, Asakawa A, Cheng K, Amitani M, Kaimoto K, Nakano M, et al. Hydrogen Improves Glycemic Control in Type1 Diabetic Animal Model by Promoting Glucose Uptake into Skeletal Muscle. PLOS ONE. 2013; 8(1):53913-53926.

Arifah SN, Atho’illah MF, Lukiati B, Lestari SR. Herbal Medicine from Single Clove Garlic Oil Extract Ameliorates Hepatic Steatosis and Oxidative Status in High Fat Diet Mice. Malays J Med Sci. 2020; 27(1):46-56.

Gofur A, Witjoro A, Arifah SN, Atho’illah MF, Annisa Y, Lestari SR. Black soybean tempeh and purple sweet potato improve sperm quality in streptozotocin-induced diabetic rats. Vet World. 2020; 13(7):112534-2540.

Gofur A, Witjoro A, Widya Ningtiyas E, Setyowati E, Aminatul Mukharromah S, Suhartini S, Atho’illah MF, Lestari SR. The ameliorative effect of black soybean and purple sweet potato to improve sperm quality through suppressing reactive oxygen species (ROS) in type 2 diabetes mellitus rat (Rattus novergicus). Sci Asia. 2018; 44(5):303-310.

Syamsul ES, Nugroho AE, Pramono S. The Antidiabetics of Combination Metformin and Purified Extract of Andrographis paniculata (Burn).F.Ness in High Fructose-Fat Fed Rats. Maj Obat Tradis. 2015; 16(3):124-132.

Masuda H, Sato A, Miyata K, Shizuno T, Oyamada A, Ishiwata K, Nakagawa Y, Asahara T. Drinking Molecular Hydrogen Water Is Beneficial to Cardiovascular Function in Diet-Induced Obesity Mice. Biol. 2021; 10(5):364-381.

Arifah SN, Lukiati B, Lestari SR. Potency of single garlic oil from Indonesian tropical plant in high fat diet-induced hyperlipidemia mice. In Solo, Indonesia; 2018. 1-5 p. [cited 2020, Aug 12]. Available from: http://aip.scitation.org/doi/abs/10.1063/1.5054514

Shah R, Subhan F, Sultan SM, Ali G, Ullah I, Ullah S. Comparative evaluation of pancreatic histopathology of rats treated with olanzapine, risperidone and streptozotocin. Braz J Pharm Sci. 2018; 54(03):1-5.

Matikainen N. Chapter 39 - Fibroblast Growth Factor 21 is a Regulator of Energy Metabolism in the Liver and Adipose Tissue. In: Watson RR, editor. Nutrition in the Prevention and Treatment of Abdominal Obesity. San Diego: Academic Press; 2014. 461-472 p.

Kajiyama S, Hasegawa G, Asano M, Hosoda H, Fukui M, Nakamura N, Kitawaki J, Imai S, Nakan K, Ohta M, Adachi T, Obayashi H, Yoshikawa T. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res. 2008; 28(3):137-143.

Xie K, Yu Y, Huang Y, Zheng L, Li J, Chen H, Han H, Hou L, Gong G, Wang G. Molecular Hydrogen Ameliorates Lipopolysaccharide-induced Acute Lung Injury in Mice through Reducing Inflammation and Apoptosis: Shock. 2012; 37(5):548-555.

Lin C-P, Chuang W-C, Lu F-J, Chen C-Y. Anti-oxidant and anti-inflammatory effects of hydrogen-rich water alleviate ethanol-induced fatty liver in mice. World J Gastroenterol. 2017; 23(27): 4920-4934.

Shao A, Wu H, Hong Y, Tu S, Sun X, Wu Q, Zhao Q, Zhang J, Sheng J. Hydrogen-Rich Saline Attenuated Subarachnoid Hemorrhage-Induced Early Brain Injury in Rats by Suppressing Inflammatory Response: Possible Involvement of NF-κB Pathway and NLRP3 Inflammasome. Mol Neurobiol. 2016; 53(5):3462-3476.

Atho’illah MF, Safitri YD, Nur’aini FD, Widyarti S, Tsuboi H, Rifa’i M. Elicited soybean extract attenuates proinflammatory cytokines expression by modulating TLR3/TLR4 activation in high−fat, high−fructose diet mice. J Ayurv Integr Med. 2021; 12(1):43-51.

Lestari SR and Rifa’i M. Regulatory T cells and antiinflammatory cytokine profile of mice fed a high-fat diet after single-bulb garlic (Allium sativum L.) oil treatment. Trop J Pharm Res. 2019; 17(11):2157.

Chen L, Ma C, Bian Y, Li J, Wang T, Su L, Lu J. Hydrogen Treatment Protects Mice Against Chronic Pancreatitis by Restoring Regulatory T Cells Loss. Cell Physiol Biochem. 2017; 44(5):2005-2016.

Barman AK, Ahmed T, Das H, Biswas B, Ali MS, Acharyya RN, Sarkar K, Dev S. Evaluation of Antidiabetic Potential of Extract of Sonneratia caseolaris (L.) Engl. Leaves against Alloxan-Induced Diabetes in Mice. Trop J Nat Prod Res. 2021; 5(1):77-83.

Ming Y, Ma Q-H, Han X-L, Li H-Y. Molecular hydrogen improves type 2 diabetes through inhibiting oxidative stress. Exp Ther Med. 2020; 20(1):359-366.

LeBaron TW, Singh RB, Fatima G, Kartikey K, Sharma JP, Ostojic SM, Gyozdjakova A, Kura B, Noda M, Mojto V, Niaz MA, and Slezak J. The Effects of 24-Week, High-Concentration Hydrogen-Rich Water on Body Composition, Blood Lipid Profiles and Inflammation Biomarkers in Men and Women with Metabolic Syndrome: A Randomized Controlled Trial. Diabetes Metab Syndr Obes Targets Ther. 2020; 13(2020):889-896.

Sobue S, Inoue C, Hori F, Qiao S, Murate T, Ichihara M. Molecular hydrogen modulates gene expression via histone modification and induces the mitochondrial unfolded protein response. Biochem Biophys Res Commun. 2017; 493(1):318-324.

Rojas J, Bermudez V, Palmar J, Martínez MS, Olivar LC, Nava M, Tomey D, Rojas M, Salazar J, Garicano C, Velasco M. Pancreatic Beta Cell Death: Novel Potential Mechanisms in Diabetes Therapy. J Diabetes Res. 2018; 2018(2):9601801-9601820.

Smirnov AV, Snigur GL, Voronkova MP. Pancreatic Islet BetaCell Apoptosis in Experimental Diabetes Mellitus (Chapter 9). Apoptosis Med. IntechOpen 2012. Available from: https://www.intechopen.com/books/apoptosis-andmedicine/pancreatic-islet-beta-cell-apoptosis-in-experimentaldiabetes-mellitus

Retnaningtyas E, Susatia B, Indrajani O, Setyabudhi V, Santoso H. Hydrogen-rich water supplementation declines advanced glycation-end products (AGE) and receptor for AGE (RAGE) in streptozotocin-induced diabetic rats. In Malang, Indonesia; 2021. 1-6 p. [cited 2021 Jun 29]. Available from: http://aip.scitation.org/doi/abs/10.1063/5.0052797