Protective Effect of Naringin in L-arginine-induced Acute Pancreatitis in Wistar Rats

Protective Role of Naringin Acute Pancreatitis

Authors

  • Navid Moznebi Esfahani Trauma Research Center, Kashan University of Medical Sciences, Kashan, Iran
  • Seyed Alireza Salimi-Tabatabaee Trauma Research Center, Kashan University of Medical Sciences, Kashan, Iran
  • Fatemeh Karamali Department of Cardiovascular Medicine, Kashan University of Medical Sciences, Kashan, Iran
  • Seyed Abbas Mirmalek Department of Surgery, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • Shima Shafagh Trauma Research Center, Kashan University of Medical Sciences, Kashan, Iran
  • Nushin Moussavi Trauma Research Center, Kashan University of Medical Sciences, Kashan, Iran

DOI:

https://doi.org/10.31661/gmj.v13i.3354

Keywords:

Naringin; L-arginine Pancreatitis; Oxidative Stress; Anti-inflammation

Abstract

Background: Acute pancreatitis is a non-infectious inflammatory disorder of the pancreas and a leading cause of hospitalization among gastrointestinal diseases, with up to 20% of patients experiencing morbidity and mortality. Naringin, a flavonoid found in fruits like oranges and tomatoes, has antioxidant and anti-inflammatory properties, making it useful in preventing and treating various diseases. This study aimed to investigate the effects of naringin on inflammation and oxidative stress in a rat model of pancreatitis. Materials and Methods: Sixty male Sprague-Dawley rats were divided into four groups. The control group received normal saline intraperitoneally (IP). Pancreatitis was induced in the sham and experimental groups using 3.2 g/kg of L-arginine IP, twice, with a one-hour interval. The experimental low dose (E-L) and high dose (E-H) groups were given 200 and 500 mg/kg of naringin IP, 30 minutes before L-arginine administration. Serum lipase, amylase, pancreatic IL-10, IL-1β, and TNF-α levels were measured. Oxidative stress markers such as superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) were also evaluated, and histopathological examination assessed tissue damage. Results: The sham group showed increased amylase and lipase levels compared to controls. Naringin significantly reduced these levels in the experimental groups. It also decreased MDA and MPO levels and increased SOD and GSH activities. TNF-α and IL-1β levels were elevated in the sham group but were reduced with naringin treatment, which increased IL-10 levels in a dose-dependent manner. Histopathological analysis revealed a dose-dependent reduction in tissue damage severity with naringin. Conclusion: Naringin administration reduced pancreatic enzyme activity and enhanced antioxidant enzyme activities in rats with pancreatitis. It also demonstrated anti-inflammatory effects, decreased TNF-α and IL-1β levels, increased IL-10 levels, and showed protective effects against tissue damage, suggesting its potential as a therapeutic agent for pancreatitis-related complications.

References

Iannuzzi JP, King JA, Leong JH, Quan J, Windsor JW, Tanyingoh D, Coward S, Forbes N, Heitman SJ, Shaheen AA, Swain M. Global incidence of acute pancreatitis is increasing over time: a systematic review and meta-analysis. Gastroenterology. 2022;162(1):122-34.

https://doi.org/10.1053/j.gastro.2021.09.043

PMid:34571026

Mederos MA, Reber HA, Girgis MD. Acute pancreatitis: a review. Jama. 2021 Jan 26;325(4):382-90.

https://doi.org/10.1001/jama.2020.20317

PMid:33496779

Matta B, Gougol A, Gao X, Reddy N, Talukdar R, Kochhar R, Goenka MK, Gulla A, Gonzalez JA, Singh VK, Ferreira M. Worldwide variations in demographics, management, and outcomes of acute pancreatitis. Clinical Gastroenterology and Hepatology. 2020;18(7):1567-75.

https://doi.org/10.1016/j.cgh.2019.11.017

PMid:31712075 PMCid:PMC9198955

Shilpa VS, Shams R, Dash KK, Pandey VK, Dar AH, Ayaz Mukarram S, Harsányi E, Kovács B. Phytochemical properties, extraction, and pharmacological benefits of naringin: a review. Molecules. 2023;28(15):5623.

https://doi.org/10.3390/molecules28155623

PMid:37570594 PMCid:PMC10419872

Fadholly A, Ansori AN, Sucipto TH. An overview of naringin: Potential anticancer compound of Citrus fruits. Research Journal of Pharmacy and Technology. 2020;13(11):5613-9.

Khaled SS, Soliman HA, Abdel-Gabbar M, Ahmed NA, El-Nahass ES, Ahmed OM. Naringin and naringenin counteract taxol-induced liver injury in Wistar rats via suppression of oxidative stress, apoptosis and inflammation. Environmental Science and Pollution Research. 2023;30(39):90892-905.

https://doi.org/10.1007/s11356-023-28454-4

PMid:37466839 PMCid:PMC10439847

Zhao H, Liu M, Liu H, Suo R, Lu C. Naringin protects endothelial cells from apoptosis and inflammation by regulating the Hippo-YAP Pathway. Bioscience reports. 2020;40(3):BSR20193431.

https://doi.org/10.1042/BSR20193431

PMid:32091090 PMCid:PMC7056449

Niu X, Sang H, Wang J. Naringenin attenuates experimental autoimmune encephalomyelitis by protecting the intact of blood-brain barrier and controlling inflammatory cell migration. The Journal of nutritional biochemistry. 2021;89:108560.

https://doi.org/10.1016/j.jnutbio.2020.108560

PMid:33249188

Mirmalek SA, Gholamrezaei Boushehrinejad A, Yavari H, Kardeh B, Parsa Y, Salimi-Tabatabaee SA, Yadollah-Damavandi S, Parsa T, Shahverdi E, Jangholi E. Antioxidant and anti-inflammatory effects of coenzyme Q10 on L-arginine-induced acute pancreatitis in rat. Oxidative medicine and cellular longevity. 2016;2016(1):5818479.

https://doi.org/10.1155/2016/5818479

PMid:27190575 PMCid:PMC4844882

Li P, Wang S, Guan X, Liu B, Wang Y, Xu K, Peng W, Su W, Zhang K. Acute and 13 weeks subchronic toxicological evaluation of naringin in Sprague-Dawley rats. Food and Chemical Toxicology. 2013;60:1-9.

https://doi.org/10.1016/j.fct.2013.07.019

PMid:23871784

Lowry O, Rosebrough N, Farr AL, Randall R. Protein measurement with the Folin phenol reagent. Journal of biological chemistry. 1951;193(1):265-75.

https://doi.org/10.1016/S0021-9258(19)52451-6

PMid:14907713

Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. Journal of investigative dermatology. 1982;78(3):206-9.

https://doi.org/10.1111/1523-1747.ep12506462

PMid:6276474

Schmidt J, Rattner DW, Lewandrowski K, Compton CC, Mandavilli U, Knoefel WT, Warshaw AL. A better model of acute pancreatitis for evaluating therapy. Annals of surgery. 1992;215(1):44.

https://doi.org/10.1097/00000658-199201000-00007

PMid:1731649 PMCid:PMC1242369

Szatmary P, Grammatikopoulos T, Cai W, Huang W, Mukherjee R, Halloran C, Beyer G, Sutton R. Acute pancreatitis: Diagnosis and treatment. Drugs. 2022;82(12):1251-76.

https://doi.org/10.1007/s40265-022-01766-4

PMid:36074322 PMCid:PMC9454414

Yang X, Yao L, Fu X, Mukherjee R, Xia Q, Jakubowska MA, Ferdek PE, Huang W. Experimental acute pancreatitis models: history, current status, and role in translational research. Frontiers in Physiology. 2020;11:614591.

https://doi.org/10.3389/fphys.2020.614591

PMid:33424638 PMCid:PMC7786374

Su KH, Cuthbertson C, Christophi C. Review of experimental animal models of acute pancreatitis. Hpb. 2006;8(4):264-86.

https://doi.org/10.1080/13651820500467358

PMid:18333137 PMCid:PMC2023897

Shirani K, Yousefsani BS, Shirani M, Karimi G. Protective effects of naringin against drugs and chemical toxins induced hepatotoxicity: A review. Phytotherapy Research. 2020;34(8):1734-44.

https://doi.org/10.1002/ptr.6641

PMid:32067280

Hernández-Aquino E, Muriel P. Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World journal of gastroenterology. 2018;24(16):1679.

https://doi.org/10.3748/wjg.v24.i16.1679

PMid:29713125 PMCid:PMC5922990

Chattopadhyay D, Sen S, Chatterjee R, Roy D, James J, Thirumurugan K. Context-and dose-dependent modulatory effects of naringenin on survival and development of Drosophila melanogaster. Biogerontology. 2016;17:383-93.

https://doi.org/10.1007/s10522-015-9624-6

PMid:26520643

Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Advances in Nutrition. 2014;5(4):404-17.

https://doi.org/10.3945/an.113.005603

PMid:25022990 PMCid:PMC4085189

Liu L, Zuo Z, Lu S, Liu A, Liu X. Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-κB activation in vivo and in vitro. Iranian journal of basic medical sciences. 2017;20(7):813.

Gopinath K, Sudhandiran G. Naringin modulates oxidative stress and inflammation in 3-nitropropionic acid-induced neurodegeneration through the activation of nuclear factor-erythroid 2-related factor-2 signalling pathway. Neuroscience. 2012;227:134-43.

https://doi.org/10.1016/j.neuroscience.2012.07.060

PMid:22871521

Zaidun NH, Thent ZC, Abd Latiff A. Combating oxidative stress disorders with citrus flavonoid: Naringenin. Life sciences. 2018;208:111-22.

https://doi.org/10.1016/j.lfs.2018.07.017

PMid:30021118

Akamo AJ, Rotimi SO, Akinloye DI, Ugbaja RN, Adeleye OO, Dosumu OA, Eteng OE, Amah G, Obijeku A, Cole OE. Naringin prevents cyclophosphamide-induced hepatotoxicity in rats by attenuating oxidative stress, fibrosis, and inflammation. Food and chemical toxicology. 2021;153:112266.

https://doi.org/10.1016/j.fct.2021.112266

PMid:33992719

Alimohammadi M, Mohammad RN, Rahimi A, Faramarzi F, Alizadeh-Navaei R, Rafiei A. The effect of immunomodulatory properties of naringenin on the inhibition of inflammation and oxidative stress in autoimmune disease models: a systematic review and meta-analysis of preclinical evidence. Inflammation Research. 2022;71(10-11):1127-42.

https://doi.org/10.1007/s00011-022-01599-7

PMid:35804246

Tsai K, Wang SS, Chen TS, Kong CW, Chang FY, Lee SD, Lu FJ. Oxidative stress: an important phenomenon with pathogenetic significance in the progression of acute pancreatitis. Gut. 1998;42(6):850-5.

https://doi.org/10.1136/gut.42.6.850

PMid:9691925 PMCid:PMC1727136

Pădureanu V, Florescu DN, Pădureanu R, Ghenea AE, Gheonea DI, Oancea CN. Role of antioxidants and oxidative stress in the evolution of acute pancreatitis. Experimental and Therapeutic Medicine. 2022;23(3):1-5.

https://doi.org/10.3892/etm.2022.11120

PMid:35126700 PMCid:PMC8794551

Shi C, Andersson R, Zhao X, Wang X. Potential role of reactive oxygen species in pancreatitis-associated multiple organ dysfunction. Pancreatology. 2005;5(4-5):492-500.

https://doi.org/10.1159/000087063

PMid:16020935

Akamo AJ, Akinloye DI, Ugbaja RN, Adeleye OO, Dosumu OA, Eteng OE, Antiya MC, Amah G, Ajayi OA, Faseun SO. Naringin prevents cyclophosphamide-induced erythrocytotoxicity in rats by abrogating oxidative stress. Toxicology Reports. 2021;8:1803-13.

https://doi.org/10.1016/j.toxrep.2021.10.011

PMid:34760624 PMCid:PMC8567332

Gelen V, Yıldırım S, Şengül E, Çınar A, Çelebi F, Küçükkalem M, Gök M. Naringin attenuates oxidative stress, inflammation, apoptosis, and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats. Asian Pacific Journal of Tropical Biomedicine. 2022;12(5):223-32.

https://doi.org/10.4103/2221-1691.343390

Han G, Lee DG. Naringin generates three types of reactive oxygen species contributing differently to apoptosis-like death in Escherichia coli. Life Sciences. 2022;304:120700.

https://doi.org/10.1016/j.lfs.2022.120700

PMid:35690109

Emran TB, Islam F, Nath N, Sutradhar H, Das R, Mitra S, Alshahrani MM, Alhasaniah AH, Sharma R. Naringin and naringenin polyphenols in neurological diseases: understandings from a therapeutic viewpoint. Life. 2022;13(1):99.

https://doi.org/10.3390/life13010099

PMid:36676048 PMCid:PMC9867091

Downloads

Published

2024-09-06

How to Cite

Moznebi Esfahani, N., Salimi-Tabatabaee, S. A., Karamali, F., Mirmalek, S. A., Shafagh, S., & Moussavi, N. (2024). Protective Effect of Naringin in L-arginine-induced Acute Pancreatitis in Wistar Rats: Protective Role of Naringin Acute Pancreatitis. Galen Medical Journal, 13, e3354. https://doi.org/10.31661/gmj.v13i.3354

Issue

Section

Original Article