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:: Volume 29, Issue 2 (3-2024) ::
__Armaghane Danesh__ 2024, 29(2): 172-184 Back to browse issues page
Effect of Empagliflozin on Hepatotoxicity Induced by Cyclophosphamide in Male Rats
E Azargun1 , I Gheitasi 2, H Sadeghi3 , I Panahi Kokhdan4 , M Azizi5 , GH Akbari4
1- Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran,
2- Department of Physiology and Pharmacology, Yasuj University of Medical Sciences, Yasuj, Iran , gheitasiizadpanah@yahoo.com
3- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran,
4- Department of Physiology and Pharmacology, Yasuj University of Medical Sciences, Yasuj, Iran
5- Department of Pathology, Yasuj University of Medical Sciences, Yasuj, Iran.
Abstract:   (627 Views)
Background & aim: Cyclophosphamide (CP) is an immunosuppressive medication which is primarily used to manage and treatt of neoplasms, including breast cancer, lymphoma and Leukemia. CP as well possesses many side effects, including hepatotoxicity which leads to mitochondrial oxidative stress, cell death and hepatic necrosis. Empagliflozin (EMPA) is a Sodium-glucose cotransporter-2 inhibitor used to treat diabetes and has antioxidant activity. The present study was designed to investigate the effect of Empagliflozin on hepatotoxicity induced by cyclophosphamide in male rats.

Methods: The present experimental study was conducted at the School of Medicine, Yasuj University of Medical Sciences in 2023. Twenty-four male Wistar rats were divided into four groups: control group, CP group, EMPA+CP group and CP+EMPA group. All groups were treated for 11 days. Moreover, blood samples were obtained and the liver was removed. Plasma levels of ALT, AST and ALP were measured. Homogenized liver tissue was used to measure malondialdehyde (MDA), Nitric Oxide (NO). Liver histology was also performed. The results were analyzed by one- way ANOVA and Tukey's Post Hoc test.

Results: The results indicated that cyclophosphamide triggered a significant increase in the plasma level of AST, ALT enzymes and the level of NO and MDA metabolites in the liver tissue (p<0.001) and increased inflammation, edema, congestion and tissue necrosis compared to the control group. The administration of Empagliflozin led to a decrease in plasma levels of AST and ALT enzymes and tissue levels of NO and MDA and decreased tissue changes compared to the cyclophosphamide group. Furthermore, Empagliflozin reduced histological changes both as prevention and as treatment.

Conclusion: According to the results of the present study, Empagliflozin can reduce the hepatotoxicity of cyclophosphamide probably with reduction of oxidative stress.

 
Keywords: Cyclophosphamide, Empagliflozin, hepatotoxicity, Liver Enzymes, Malondialdehyde.
Full-Text [PDF 836 kb]   (91 Downloads)    
Type of Study: Research | Subject: Physiology
Received: 2023/10/10 | Accepted: 2023/12/26 | Published: 2024/03/16
References
1. Williams R. Global Challenges in Liver Disease. Hepatology 2006; 44: 521-6.## [DOI:10.1002/hep.21347] [PMID]
2. Ramadori G, Moriconi F, Malik I, Dudas J. Physiology and pathophysiology of liver inflammation, damage and repair. Journal of Physiology and Pharmacology: an official Journal of the Polish Physiological Society 2008; 59(Suppl 1): 107-17.##
3. Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. Journal of Renal Injury Prevention 2015; 4(2): 20-7.##
4. Sharma U, Pal D, Prasad R. Alkaline phosphatase: an overview. Indian Journal of Clinical Biochemistry 2014; 29(3): 269-78.## [DOI:10.1007/s12291-013-0408-y] [PMID] []
5. Okada M, Sogo A, Ohnishi N. Glycation reaction of aspartate aminotransferase by various carbohydrates in an in vitro system. The Journal of Nutritional Biochemistry 1994; 5(10): 485-9.## [DOI:10.1016/0955-2863(94)90027-2]
6. McGill M R. The past and present of serum aminotransferases and the future of liver injury biomarkers. EXCLI J 2016; 15: 817-828.##
7. Volpe DA, Ellison CD, Parchment RE, Grieshaber CK, Faustino PJ. Effects of amitriptyline and fluoxetine upon the in vitro proliferation of tumor cell lines. J Exp Ther Oncol 2003; 3(4): 169-84.## [DOI:10.1046/j.1359-4117.2003.01091.x] [PMID]
8. Ahmed AR, Hombal SM. Cyclophosphamide (Cytoxan). A review on relevant pharmacology and clinical uses. Journal of the American Academy of Dermatology 1984; 11(6): 1115-26.## [DOI:10.1016/S0190-9622(84)80193-0] [PMID]
9. Oyagbemi AA, Omobowale OT, Asenuga ER, Akinleye AS, Ogunsanwo RO, Saba AB. Cyclophosphamide-induced hepatotoxicity in wistar Rats: The modulatory role of gallic acid as a hepatoprotective and chemopreventive phytochemical. International Journal of Preventive Medicine. 2016; 7:51. ## [DOI:10.4103/2008-7802.177898] [PMID] []
10. Cuce G, Çetinkaya S, Koc T, Esen HH, Limandal C, Balcı T, et al. Chemoprotective effect of vitamin E in cyclophosphamide-induced hepatotoxicity in rats. Chemico-biological Interactions 2015; 232: 7-11.## [DOI:10.1016/j.cbi.2015.02.016] [PMID]
11. Temel Y, Kucukler S, Yıldırım S, Caglayan C, Kandemir FM. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation and apoptosis. Naunyn-Schmiedeberg's Archives of Pharmacology 2020; 393(3): 325-37.## [DOI:10.1007/s00210-019-01741-z] [PMID]
12. Novikov A, Vallon V. Sodium glucose cotransporter 2 inhibition in the diabetic kidney. Curr Opin Nephrol Hypertens 2016; 25: 50-8.## [DOI:10.1097/MNH.0000000000000187] [PMID] []
13. Khamseh ME. Effect of empagliflozin on liver steatosis and fibrosis in patients with non-alcoholic fatty liver disease without diabetes: A randomized, double-blind, placebo-controlled trial. Adv Ther 2020; 37: 4697-708.## [DOI:10.1007/s12325-020-01498-5] [PMID] []
14. Nami Lee, Yu Jung Heo, Sung-E Choi, Ja Young Jeon, Seung Jin Han, Dae Jung Kim, et al. Anti-inflammatory effects of empagliflozin and gemigliptin on lps-stimulated macrophage via the IKK/NF- κ B, MKK7/JNK and JAK2/STAT1 signalling pathways. J Immunol Res 2021; 2021: 9944880. ## [DOI:10.1155/2021/9944880] [PMID] []
15. Li C, Zhang J, Xue M, Li X, Han F, Liu X, et al. SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovascular Diabetology 2019; 18: 1-3.## [DOI:10.1186/s12933-019-0816-2] [PMID] []
16. Doustimotlagh AH, Panahi Kokhdan E, Vakilpour H, Khalvati B, Jafari Barmak M, Sadeghi H and Asfaram A. Protective effect of Nasturtium officinale R . Br and quercetin against cyclophosphamide-induced hepatotoxicity in rats. Mol Biol Rep 2020; 47(7): 5001-12.## [DOI:10.1007/s11033-020-05556-7] [PMID]
17. Marwan A ElBaset , Rana S Salem , Fairouz Ayman , Nadeen Ayman , Nooran Shaban , Sherif M Afifi ,et all. Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis. Antioxidants 2022 Oct 30;11(11):2152. https://doi.org/10.3390/antiox11112152 [DOI:10.3390/antiox11112152.##] [PMID] []
18. Gungor H, Ekici M, Karatas O, Dik B. Protective effect of Allium Scorodoprasum L. ethanolic extract in cyclophosphamide- induced hepatotoxicity model in rats Short Title: Allium Scorodoprasum L. extract can be protective in hepatotoxicity. J Pharm Pharmacol 2023; 75(5): 625-34.## [DOI:10.1093/jpp/rgad002] [PMID]
19. Hamzeh M. Hosseinimehr SJ, Khalatbary AR, Mohammadi HR, Dashti A , Talebpour Amiri F. Atorvastatin mitigates cyclophosphamide-induced hepatotoxicity via suppression of oxidative stress and apoptosis in rat model. Res Pharm Sci 2018; 13(5): 440-9.## [DOI:10.4103/1735-5362.236837] [PMID] []
20. Cuce G, Çetinkaya S, Koc T, Hasan Esen H, Limandal C, Balcı T, et al. Chemoprotective effect of vitamin E in cyclophosphamide-induced hepatotoxicity in rats. Chemico-Biological Interactions 2015; 232: 7-11.## [DOI:10.1016/j.cbi.2015.02.016] [PMID]
21. Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M. et al. Hepatoprotective effect of SGLT2 inhibitor on nonalcoholic fatty liver disease. Diab Res Open Access 2020; 2(S1): 17-25.## [DOI:10.36502/2020/droa.6159]
22. El-Kashef DH , Sewilam HM . Empagliflozin mitigates methotrexate-induced hepatotoxicity: Targeting ASK-1/JNK/Caspase-3 pathway. Int Immunopharmacol 2023; 114: 109494.## [DOI:10.1016/j.intimp.2022.109494] [PMID]
23. Simental Mendía M, Sanchez García A, Rodríguez Ramírez M, Simental Mendía L E. Effect of sodium-glucose co-transporter 2 inhibitors on hepatic parameters: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2021; 163: 105319. ## [DOI:10.1016/j.phrs.2020.105319] [PMID]
24. Amir Mohamed Abdelhamid, Ahmed Ramadan Elsheakh, Rania Ramadan Abdelaziz, Ghada Mohamed Suddek. Empagliflozin ameliorates ethanol-induced liver injury by modulating NF-κB/Nrf-2/PPAR-γ interplay in mice. Life Sci 2020; 256: 117908. ## [DOI:10.1016/j.lfs.2020.117908] [PMID]
25. Manar G. Helal. Empagliflozin attenuates cyclophosphamide-induced hepatotoxicity via targeting Nrf2/HO-1 signaling, oxidative stress, and inflammation. World J Pharm Sci 2019; 7(11): 49-59.##
26. Ramezani S, Javadi I, Panahi Kokhdan E, Omidifar N, Nikbakht J, Sadeghi H. et al. Protective and therapeutic effects of ethanolic extract of Nasturtium officinale (watercress) and vitamin E against bleomycin-induced pulmonary fibrosis in rats. Res Pharm Sci 2021; 16(1): 94-102.## [DOI:10.4103/1735-5362.305192] [PMID] []
27. Casanova NA , Simoniello MF, Lopez Nigro M M , Carballo M A. Modulator effect of watercress against cyclophosphamide-induced oxidative stress in mice. Medicina(B Aires) 2017; 77(3): 201-6.##
28. Mohammad FA , Ahmed OA , Majed HS , Ahmad JAA , Saeed A , Hina R. et al. Therapeutic Potential of Capsaicin against Cyclophosphamide-Induced Liver Damage. J Clin Med 2023; 12(3): 911.## [DOI:10.3390/jcm12030911] [PMID] []
29. Oyagbemi AA, Omobowale OT, Asenuga ER, Akinleye AS, Ogunsanwo RO, Saba AB. Cyclophosphamide-induced hepatotoxicity in wistar rats: The modulatory role of gallic acid as a hepatoprotective and chemopreventive phytochemical. Int J Prev Med 2016; 7: 51. ## [DOI:10.4103/2008-7802.177898] [PMID] []
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Azargun E, Gheitasi I, Sadeghi H, Panahi Kokhdan I, Azizi M, Akbari G. Effect of Empagliflozin on Hepatotoxicity Induced by Cyclophosphamide in Male Rats. armaghanj 2024; 29 (2) :172-184
URL: http://armaghanj.yums.ac.ir/article-1-3535-en.html


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Volume 29, Issue 2 (3-2024) Back to browse issues page
ارمغان دانش Armaghane Danesh
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