Hassan, N., Kamel, G., Fayed, H., Korany, R., Ramadan, A. (2025). Ertugliflozin, a SGLT-2 Inhibitor, Guards Against Thioacetamide-induced Liver Fibrosis: The Nrf2/HO-1 and TLR4/ TGF-β1 Pathways. Journal of Applied Veterinary Sciences, 10(3), 34-47. doi: 10.21608/javs.2025.372525.1573
Nourhan Hussien Hassan; Gehan M. Kamel; Hany M. Fayed; Reda M.S. Korany; Amer Ramadan. "Ertugliflozin, a SGLT-2 Inhibitor, Guards Against Thioacetamide-induced Liver Fibrosis: The Nrf2/HO-1 and TLR4/ TGF-β1 Pathways". Journal of Applied Veterinary Sciences, 10, 3, 2025, 34-47. doi: 10.21608/javs.2025.372525.1573
Hassan, N., Kamel, G., Fayed, H., Korany, R., Ramadan, A. (2025). 'Ertugliflozin, a SGLT-2 Inhibitor, Guards Against Thioacetamide-induced Liver Fibrosis: The Nrf2/HO-1 and TLR4/ TGF-β1 Pathways', Journal of Applied Veterinary Sciences, 10(3), pp. 34-47. doi: 10.21608/javs.2025.372525.1573
Hassan, N., Kamel, G., Fayed, H., Korany, R., Ramadan, A. Ertugliflozin, a SGLT-2 Inhibitor, Guards Against Thioacetamide-induced Liver Fibrosis: The Nrf2/HO-1 and TLR4/ TGF-β1 Pathways. Journal of Applied Veterinary Sciences, 2025; 10(3): 34-47. doi: 10.21608/javs.2025.372525.1573
Ertugliflozin, a SGLT-2 Inhibitor, Guards Against Thioacetamide-induced Liver Fibrosis: The Nrf2/HO-1 and TLR4/ TGF-β1 Pathways
1Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Egypt
2Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt
3Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt; Department of Pathology, Faculty of Veterinary Medicine, Egyptian- Chinese University, Egypt
Receive Date: 02 April 2025,
Revise Date: 07 May 2025,
Accept Date: 13 May 2025
Abstract
Hepatic fibrogenesis is considered an epidemic health problem since it can lead to several insults that can be fatal. Ertugliflozin (Ertu), an inhibitor of the sodium-glucose cotransporter-2 (SGLT2), is one of the most recent anti-diabetic medications used to treat type 2 diabetes mellitus (T2DM). In a variety of human and animal models, SGLT2 inhibitors demonstrated anti-inflammatory, anti-fibrotic, and antioxidant qualities. Consequently, we designed the present investigation to clarify the preventive role of ertugliflozin in male rat liver fibrosis brought on by thioacetamide (TAA) as well as the anticipated mechanisms. 24 rats were divided into four groups: “a control group, “TAA group” (received intraperitoneal injections of 100 mg/kg b.wt. twice a week for six weeks), and "TAA + Ertu" groups (received oral Ertu at doses of 5 and 10 mg/kg b.wt. for four weeks in addition to TAA injections). Ertugliflozin promoted hepatic antioxidant effects by considerably increasing HO-1, Nrf2 protein and mRNA expression, GSH and SOD levels, and lowering hepatic MDA content. It also greatly reduced TAA-induced changes in liver function measures. Additionally, ertugliflozin suppressed the elevated levels of “PI3K, TGF-β1, α SMA, and caspase3” and enhanced the hepatic anti-inflammatory state by declining the pro-inflammatory cytokines “TNF-α, IL-6, and TLR4” levels. Histological examination showed that ertugliflozin significantly inhibited the liver alterations caused by TAA. Our findings imply that ertugliflozin’s hepatoprophylactic effects may be mediated by improving antioxidant capacities and reducing inflammatory signals by modifying the Nrf2/HO-1 and TLR4/TGF-β1 pathways.
ABD EL-RAHMAN, S. S., and FAYED, H. M., 2019. Targeting AngII/AT1R signaling pathway by perindopril inhibits ongoing liver fibrosis in rat. J Tissue Eng Regen Med, 13(12): 2131-2141. https://doi.org/10.1002/term.2940
ABD ULJALEEL, A. Q., and HASSAN, E. S., 2023. Protective Effect of Ertugliflozin against Acute Lung Injury Caused by Endotoxemia Model in Mice. Iranian Journal of War and Public Health, 15(1): 67-75. http://dx.doi.org/10.58209/ijwph.15.1.67.
ABDELMAGEED, M. E., and ABDELRAHMAN, R. S., 2023. Canagliflozin attenuates thioacetamide-induced liver injury through modulation of HMGB1/RAGE/TLR4 signaling pathways. Life Sciences, 322: 121654. https://doi.org/10.1016/j.lfs.2023.121654
ABDEL-RAHMAN, R. F., FAYED, H. M., ASAAD, G. F., OGALY, H. A., HESSIN, A. F., SALAMA, A. A. A., ABD EL-RAHMAN, S. S., ARBID, M. S., and MOHAMED, M. A. E., 2021. The involvement of TGF-β1 /FAK/α-SMA pathway in the antifibrotic impact of rice bran oil on thioacetamide-induced liver fibrosis in rats. PLoS One, 16(12): e0260130. https://doi.org/10.1371/journal.pone.0260130
ABDEL-RAHMAN, R. F., FAYED, H. M., OGALY, H. A., HUSSEIN, R. A., and RASLAN, M. A., 2022. Phytoconstituents of Sansevieria suffruticosa N.E.Br. Leaves and Its Hepatoprotective Effect via Activation of the NRF2/ARE Signaling Pathway in an Experimentally Induced Liver Fibrosis Rat Model. Chemistry & Biodiversity, 19(4): e202100960. https://doi.org/10.1002/cbdv.202100960
ABU-RISHA, S. E., SOKAR, S. S., ELBOHOTY, H. R., and ELSISI, A. E., 2023. Combined carvacrol and cilostazol ameliorate ethanol-induced liver fibrosis in rats: Possible role of SIRT1/Nrf2/HO-1 pathway. International Immunopharmacology, 116: 109750. https://doi.org/10.1016/j.intimp.2023.109750
ALSHARIF, I. A., FAYED, H. M., ABDEL-RAHMAN, R. F., ABD-ELSALAM, R. M., and OGALY, H. A., 2022. Miconazole Mitigates Acetic Acid-Induced Experimental Colitis in Rats: Insight into Inflammation, Oxidative Stress and Keap1/Nrf-2 Signaling Crosstalk. Biology, 11(2): 303. https://www.mdpi.com/2079-7737/11/2/303
ASLAM, A., SHEIKH, N., SHAHZAD, M., SAEED, G., FATIMA, N., and AKHTAR, T., 2022. Quercetin ameliorates thioacetamide-induced hepatic fibrosis and oxidative stress by antagonizing the Hedgehog signaling pathway. J. Cell. Biochem., 123(8): 1356-1365.https://doi.org/10.1002/jcb.30296
ASSINDER, S. J., DONG, Q., KOVACEVIC, Z., and RICHARDSON, D. R., 2009. The TGF-beta, PI3K/Akt and PTEN pathways: established and proposed biochemical integration in prostate cancer. Biochem J, 417(2): 411-421. https://doi.org/10.1042/BJ20081610
BAI, T., YANG, Y., WU, Y.-L., JIANG, S., LEE, J. J., LIAN, L.-H., and NAN, J.-X., 2014. Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation by activating LKB1-AMPK signaling pathway in mice. International immunopharmacology, 19(2): 351-357. https://doi.org/10.1016/j.intimp.2014.02.006
BANCROFT, J. D., and GAMBLE, M., 2008. Theory and practice of histological techniques, Elsevier health sciences.
BANNI, M., MESSAOUDI, I., SAID, L., EL HENI, J., KERKENI, A., and SAID, K., 2010. Metallothionein gene expression in liver of rats exposed to cadmium and supplemented with zinc and selenium. Arch Environ Contam Toxicol, 59(3): 513-519. https://doi.org/10.1007/s00244-010-9494-5
BARAKA, S. M., MOWAAD, N. A., IBRAHIM, S., KORANY, R. M. S., EL-SAYED, A. F., HASSAN, A. A., and MANSOUR, D. A., 2023. Green synthesized cerium oxide nanoparticles ameliorate hepatic and cognitive dysfunctions in thioacetamide-induced hepatic encephalopathy in rats: Modulation of TLR-4/NF-κB/Caspase-3 signaling pathways. Journal of Drug Delivery Science and Technology, 87: 104846. https://doi.org/10.1016/j.jddst.2023.104846
BHATTACHARYYA, A., CHATTOPADHYAY, R., MITRA, S. and CROWE, S. E., 2014. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev, 94(2): 329-354. https://doi.org/10.1152/physrev.00040.2012
BRENNER, D. A. 2009. Molecular pathogenesis of liver fibrosis. Trans Am Clin Climatol Assoc, 120: 361-368.
CASO, J. R., PRADILLO, J. M., HURTADO, O., LORENZO, P., MORO, M. A., and LIZASOAIN, I., 2007. Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation, 115(12): 1599-1608. https://doi.org/10.1161/CIRCULATIONAHA.106.603431
CHEN, X., DING, C., LIU, W., LIU, X., ZHAO, Y., ZHENG, Y., DONG, L., KHATOON, S., HAO, M., PENG, X., ZHANG, Y., and CHEN, H., 2021. Abscisic acid ameliorates oxidative stress, inflammation, and apoptosis in thioacetamide-induced hepatic fibrosis by regulating the NF-кB signaling pathway in mice. Eur. J. Pharmacol., 891: 173652. https://doi.org/10.1016/j.ejphar.2020.173652
CHU, X., ZHANG, X., GONG, X., ZHOU, H., and CAI, C., 2020. Effects of hyperoxia exposure on the expression of Nrf2 and heme oxygenase-1 in lung tissues of premature rats. Molecular and Cellular Probes, 51: 101529. https://doi.org/10.1016/j.mcp.2020.101529
CROTEAU, D., LUPTAK, I., CHAMBERS, J. M., HOBAI, I., PANAGIA, M., PIMENTEL, D. R., SIWIK, D. A., QIN, F., and COLUCCI, W. S., 2021. Effects of sodium‐glucose linked transporter 2 inhibition with ertugliflozin on mitochondrial function, energetics, and metabolic gene expression in the presence and absence of diabetes mellitus in mice. Journal of the American Heart Association, 10(13): e019995. https://doi.org/10.1161/JAHA.120.019995
DEABES, D. A. H., EL-ABD, E. A. W., BARAKA, S. M., EL-GENDY, Z. A., KORANY, R. M. S., and ELBATANONY, M. M., 2025. Metabolomics analyses and comparative insight to neuroprotective potential of unripe fruits and leaves of Citrus aurantium ethanolic extracts against cadmium-induced rat brain dysfunction: involvement of oxidative stress and akt-mediated CREB/BDNF and GSK3β/NF-κB signaling pathways. Metab Brain Dis, 40(1): 89. https://doi.org/10.1007/s11011-024-01513-6
DEMIREL, U., YALNIZ, M., AYGÜN, C., ORHAN, C., TUZCU, M., SAHIN, K., ÖZERCAN, İ. H., and BAHÇECIOĞLU, İ. H., 2012. Allopurinol ameliorates thioacetamide-induced acute liver failure by regulating cellular redox-sensitive transcription factors in rats. Inflammation, 35: 1549-1557. https://doi.org/10.1007/s10753-012-9470-5
DEROSA, G., and MAFFIOLI, P., 2018. Ertugliflozin: a sodium-glucose cotransporter-2 (SGLT-2) inhibitor for glycemic control in type 2 diabetes. Therapeutics and Clinical Risk Management: 1637-1640. https://doi.org/10.2147/TCRM.S137068
ĐURAŠEVIĆ, S., PEJIĆ, S., GRIGOROV, I., NIKOLIĆ, G., MITIĆ-ĆULAFIĆ, D., DRAGIĆEVIĆ, M., ĐORĐEVIĆ, J., TODOROVIĆ VUKOTIĆ, N., ĐORĐEVIĆ, N., TODOROVIĆ, A., DRAKULIĆ, D., VELJKOVIĆ, F., PAJOVIĆ, S. B., and TODOROVIĆ, Z., 2021. Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. Antioxidants (Basel), 10(6). https://doi.org/10.3390/antiox10060911
ELBASET, M. A., MOHAMED, B., HESSIN, A., ABD EL-RAHMAN, S. S., ESATBEYOGLU, T., AFIFI, S. M., and FAYED, H. M., 2024. Nrf2/HO-1, NF-κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats. J Cell Mol Med, 28(3): e18116. https://doi.org/10.1111/jcmm.18116
ELBASET, M. A., MOHAMED, B., MOUSTAFA, P. E., MANSOUR, D. F., AFIFI, S. M., ESATBEYOGLU, T., ABDELRAHMAN, S. S. M., and FAYED, H. M., 2023. Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thioacetamide: Role of the PI3K/Akt and TLR4 Signaling Pathways. Oxid Med Cell Longev, 2023: 5514248. https://doi.org/10.1155/2023/5514248
ELEFTHERIADIS, T., PISSAS, G., LIAKOPOULOS, V., and STEFANIDIS, I., 2016. Cytochrome c as a potentially clinical useful marker of mitochondrial and cellular damage. Frontiers in immunology, 7: 279. https://doi.org/10.3389/fimmu.2016.00279
EL-GENDY, Z. A., RAMADAN, A., EL-BATRAN, S. A., AHMED, R. F., EL-MARASY, S. A., ABD EL-RAHMAN, S. S., and YOUSSEF, S., 2021. Carvacrol hinders the progression of hepatic fibrosis via targeting autotaxin and thioredoxin in thioacetamide-induced liver fibrosis in rat. Hum Exp Toxicol, 40(12): 2188-2201. https://doi.org/10.1177/09603271211026729
EL-KASHEF, D. H., and SERRYA, M. S., 2019. Sitagliptin ameliorates thioacetamide-induced acute liver injury via modulating TLR4/NF-KB signaling pathway in mice. Life Sciences, 228: 266-273. https://doi.org/10.1016/j.lfs.2019.05.019
EL-KASHEF, D. H., and SHARAWY, M. H., 2018. Venlafaxine mitigates cisplatin-induced nephrotoxicity via down-regulating apoptotic pathway in rats. Chemico-biological interactions, 290: 110-118. https://doi.org/10.1016/j.cbi.2018.05.015
EL-MAKSOUD, A. A. A., KORANY, R. M. S., EL-GHANY, I. H. A., EL-BELTAGI, H. S., and AMBRÓSIO F. DE GOUVEIA, G. M., 2020. Dietary solutions to dyslipidemia: Milk protein-polysaccharide conjugates as liver biochemical enhancers. Journal of Food Biochemistry, 44(3): e13142. https://doi.org/10.1111/jfbc.13142
ELRAKAYBI, A., LAUBNER, K., ZHOU, Q., HUG, M. J., and SEUFERT, J., 2022. Cardiovascular protection by SGLT2 inhibitors - Do anti-inflammatory mechanisms play a role? Molecular Metabolism, 64: 101549. https://doi.org/10.1016/j.molmet.2022.101549
FARJAM, M., DEHDAB, P., ABBASSNIA, F., MEHRABANI, D., TANIDEH, N., PAKBAZ, S., and IMANIEH, M., 2012. Thioacetamide-induced acute hepatic encephalopathy in rat: behavioral, biochemical and histological changes. Iranian Red Crescent medical journal, 14(3): 164.
FRIAS, J. P. 2019. Fixed-dose combination of ertugliflozin and metformin hydrochloride for the treatment of type 2 diabetes. Expert Review of Endocrinology & Metabolism, 14(2): 75-83. https://doi.org/10.1080/17446651.2019.1571908
FU, Y., ZHENG, S., LIN, J., RYERSE, J., and CHEN, A., 2008. Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. Molecular pharmacology, 73(2): 399-409. https://doi.org/10.1124/mol.107.039818
GHOSH, S., SARKAR, A., BHATTACHARYYA, S., and SIL, P. C., 2016. Silymarin protects mouse liver and kidney from thioacetamide induced toxicity by scavenging reactive oxygen species and activating PI3K-Akt pathway. Frontiers in pharmacology, 7: 481. https://doi.org/10.3389/fphar.2016.00481
HASSAN, M., IBRAHIM, M. A., HAFEZ, H. M., MOHAMED, M. Z., ZENHOM, N. M., and ABD ELGHANY, H. M., 2019. Role of Nrf2/HO-1 and PI3K/Akt Genes in the Hepatoprotective Effect of Cilostazol. Curr Clin Pharmacol, 14(1): 61-67. https://doi.org/10.2174/1574884713666180903163558
HASSAN, N. H., KAMEL, G. M., FAYED, H. M., KORANY, R. M. S., and RAMADAN, A., 2025. Dapagliflozin alleviates thioacetamide induced-liver fibrosis in rats via controlling the Nrf2/HO-1 and TLR4/TGF-β1/PI3K signaling pathways. Immunopharmacol Immunotoxicol, 10.1080/08923973.2025.2496661: 1-14. https://doi.org/10.1080/08923973.2025.2496661
HUSSEIN, R. M., SAWY, D. M., KANDEIL, M. A., and FARGHALY, H. S., 2021. Chlorogenic acid, quercetin, coenzyme Q10 and silymarin modulate Keap1-Nrf2/heme oxygenase-1 signaling in thioacetamide-induced acute liver toxicity. Life Sciences, 277: 119460. https://doi.org/10.1016/j.lfs.2021.119460
IBRAHIM, M. Y., ALAMRI, Z. Z., JUMA, A. S., HAMOOD, S. A., SHAREEF, S. H., ABDULLA, M. A., and JAYASH, S. N., 2023. Hepatoprotective effects of biochanin A on thioacetamide-induced liver cirrhosis in experimental rats. Molecules, 28 (22): 7608. https://doi.org/10.3390/molecules28227608
IKRAM, M., SAEED, K., KHAN, A., MUHAMMAD, T., KHAN, M. S., JO, M. G., REHMAN, S. U., and KIM, M. O., 2019. Natural dietary supplementation of curcumin protects mice brains against ethanol-induced oxidative stress-mediated neurodegeneration and memory impairment via Nrf2/TLR4/RAGE signaling. Nutrients, 11(5): 1082. https://doi.org/10.3390/nu11051082
KHALIQ, A., BADSHAH, H., SHAH, Y., REHMAN, I. U., KHAN, K. U., MING, L. C., and CHENG, M. H., 2024. The effect of ertugliflozin in patients with nonalcoholic fatty liver disease associated with type 2 diabetes mellitus: A randomized controlled trial. Medicine, 103(45): e40356. https://doi.org/10.1097/MD.0000000000040356
KIM, H. Y., YU, J. H., CHON, Y. E., KIM, S. U., KIM, M. N., HAN, J. W., LEE, H. A., JIN, Y. J., AN, J., CHOI, M., and JUN, D. W., 2024. Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis. Clin Mol Hepatol, 30(Suppl): S199-s213. https://doi.org/10.3350/cmh.2024.0351
KULKARNI, A. A., THATCHER, T. H., OLSEN, K. C., MAGGIRWAR, S. B., PHIPPS, R. P., and SIME, P. J., 2011. PPAR-γ ligands repress TGFβ-induced myofibroblast differentiation by targeting the PI3K/Akt pathway: implications for therapy of fibrosis. PLoS One, 6(1): e15909. https://doi.org/10.1371/journal.pone.0015909
LEE, K. C., HSU, W. F., HSIEH, Y. C., CHAN, C. C., YANG, Y. Y., HUANG, Y. H., HOU, M. C., and LIN, H. C., 2019. Dabigatran Reduces Liver Fibrosis in Thioacetamide-Injured Rats. Dig Dis Sci, 64(1): 102-112. https://doi.org/10.1007/s10620-018-5311-1
LI, C., ZHANG, J., XUE, M., LI, X., HAN, F., LIU, X., XU, L., LU, Y., CHENG, Y., and LI, T., 2019. SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovascular diabetology, 18: 1-13. https://doi.org/10.1186/s12933-019-0816-2
MEI, X., XU, D., XU, S., ZHENG, Y., and XU, S., 2012. Novel role of Zn (II)-curcumin in enhancing cell proliferation and adjusting proinflammatory cytokine-mediated oxidative damage of ethanol-induced acute gastric ulcers. Chemico-biological interactions, 197(1): 31-39. https://doi.org/10.1016/j.cbi.2012.03.006
MI, X. J., HOU, J. G., JIANG, S., LIU, Z., TANG, S., LIU, X. X., WANG, Y. P., CHEN, C., WANG, Z., and LI, W., 2019. Maltol Mitigates Thioacetamide-induced Liver Fibrosis through TGF-β1-mediated Activation of PI3K/Akt Signaling Pathway. J Agric Food Chem, 67(5): 1392-1401. https://doi.org/10.1021/acs.jafc.8b05943
MOELLMANN, J., MANN, P. A., KAPPEL, B. A., KAHLES, F., KLINKHAMMER, B. M., BOOR, P., KRAMANN, R., GHESQUIERE, B., LEBHERZ, C., MARX, N., and LEHRKE, M., 2022. The sodium-glucose co-transporter-2 inhibitor ertugliflozin modifies the signature of cardiac substrate metabolism and reduces cardiac mTOR signalling, endoplasmic reticulum stress and apoptosis. Diabetes, Obesity and Metabolism, 24(11): 2263-2272. https://doi.org/10.1111/dom.14814
MOHAMMED, O. S., ATTIA, H. G., MOHAMED, B., ELBASET, M. A., and FAYED, H. M., 2023. Current investigations for liver fibrosis treatment: between repurposing the FDA-approved drugs and the other emerging approaches. J Pharm Pharm Sci, 26: 11808. https://doi.org/10.3389/jpps.2023.11808
MUKHERJEE, S., KARMAKAR, S., and BABU, S. P., 2016. TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review. Braz J Infect Dis, 20(2): 193-204. https://doi.org/10.1016/j.bjid.2015.10.011
NAIF ALSUHAYMI, M. A., AYA SHOKRY, HANY MOAWAD FAYED, BASSIM MOHAMED, SHERIF AFIFI, TUBA ESATBEYOGLU, REDA KORANY and MARAWAN ELBASET, 2025. Remogliflozin Protective Role against Experimental Liver Fibrosis by Activating AMPK/SIRT1/Nrf2 and Suppressing NF-κB Pathways. Frontiers in Pharmacology, 16: 1586231. 10.3389/fphar.2025.1586231.
O'CONNELL, M. A., and HAYES, J. D., 2015. The Keap1/Nrf2 pathway in health and disease: from the bench to the clinic. Biochemical Society Transactions, 43(4): 687-689. https://doi.org/10.1042/BST20150069
PANG, B., ZHANG, L.-L., LI, B., SUN, F. X., and WANG, Z.-D., 2023. The sodium glucose co-transporter 2 inhibitor ertugliflozin for Alzheimer's disease: Inhibition of brain insulin signaling disruption-induced tau hyperphosphorylation. Physiology & behavior, 263: 114134. https://doi.org/10.1016/j.physbeh.2023.114134
QIANG, S., NAKATSU, Y., SENO, Y., FUJISHIRO, M., SAKODA, H., KUSHIYAMA, A., MORI, K., MATSUNAGA, Y., YAMAMOTOYA, T., KAMATA, H., and ASANO, T., 2015. Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus. Diabetol Metab Syndr, 7: 104. https://doi.org/10.1186/s13098-015-0102-8
RAMADAN, A., AFIFI, N., YASSIN, N. Z., ABDEL-RAHMAN, R. F., ABD EL-RAHMAN, S. S., and FAYED, H. M., 2018. Mesalazine, an osteopontin inhibitor: The potential prophylactic and remedial roles in induced liver fibrosis in rats. Chem Biol Interact, 289: 109-118. https://doi.org/10.1016/j.cbi.2018.05.002
RAMADAN, A., KAMEL, G., AWAD, N. E., SHOKRY, A. A., and FAYED, H. M., 2020. The pharmacological effect of apricot seeds extracts and amygdalin in experimentally induced liver damage and hepatocellular carcinoma. J Herbmed Pharmacol, 9(4): 400-407. https://doi.org/10.34172/jhp.2020.50
RASLAN, M., ABDEL RAHMAN, R., FAYED, H., OGALY, H., and FIKRY, R., 2021. Metabolomic Profiling of Sansevieria trifasciata hort ex. Prain Leaves and Roots by HPLC-PAD-ESI/MS and its Hepatoprotective Effect via Activation of the NRF2/ARE Signaling Pathway in an Experimentally Induced Liver Fibrosis Rat Model. Egyptian Journal of Chemistry, 64(11): 6647-6671. https://doi.org/10.21608/ejchem.2021.78970.3877
SATTA, S., MAHMOUD, A. M., WILKINSON, F. L., YVONNE ALEXANDER, M., and WHITE, S. J., 2017. The Role of Nrf2 in Cardiovascular Function and Disease. Oxid Med Cell Longev, 2017: 9237263. https://doi.org/10.1155/2017/9237263
SHAMSELDEAN, M. S. M., ATTIA, M. M., KORANY, R. M. S., OTHAMN, N. A., and ALLAM, S. F. M., 2022. Insecticidal efficacy of nanomaterials used to control mosquito, Culex quinquefasciatus Say, 1823 with special reference to their hepatotoxicity in rats. Biosci Rep, 42(7). https://doi.org/10.1042/BSR20220630
SHIN, S. M., YANG, J. H., and KI, S. H., 2013. Role of the Nrf2‐ARE pathway in liver diseases. Oxidative medicine and cellular longevity, 2013(1): 763257. https://doi.org/10.1155/2013/763257
TIAN, Y., LI, Z., SHEN, B., ZHANG, Q., and FENG, H., 2017. Protective effects of morin on lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting TLR4/NF-κB and activating Nrf2/HO-1 signaling pathways. International immunopharmacology, 45: 148-155. https://doi.org/10.1016/j.intimp.2017.02.010
TSAI, K.-F., CHEN, Y.-L., CHIOU, T. T.-Y., CHU, T.-H., LI, L.-C., NG, H.-Y., LEE, W.-C., and LEE, C.-T., 2021. Emergence of SGLT2 Inhibitors as Powerful Antioxidants in Human Diseases. Antioxidants, 10(8): 1166. https://doi.org/10.3390/antiox10081166
VIVIAN, E. M. 2014. Sodium-glucose co-transporter 2 (SGLT2) inhibitors: a growing class of antidiabetic agents. Drugs in context, 3: 212264. https://doi.org/10.7573/dic.212264
WANG, Y., LUO, W., HAN, J., KHAN, Z. A., FANG, Q., JIN, Y., CHEN, X., ZHANG, Y., WANG, M., QIAN, J., HUANG, W., LUM, H., WU, G., and LIANG, G., 2020. MD2 activation by direct AGE interaction drives inflammatory diabetic cardiomyopathy. Nat Commun, 11(1): 2148. https://doi.org/10.1038/s41467-020-15978-3
WU, W., LI, Y., WU, Y., ZHANG, Y., WANG, Z., and LIU, X., 2015. Lutein suppresses inflammatory responses through Nrf2 activation and NF‐κB inactivation in lipopolysaccharide‐stimulated BV‐2
YAMADA, K. M., and ARAKI, M., 2001. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci, 114(Pt 13): 2375-2382. https://doi.org/10.1242/jcs.114.13.2375
YAMASHITA, Y., UEYAMA, T., NISHI, T., YAMAMOTO, Y., KAWAKOSHI, A., SUNAMI, S., IGUCHI, M., TAMAI, H., UEDA, K., ITO, T., TSURUO, Y., and ICHINOSE, M., 2014. Nrf2-inducing anti-oxidation stress response in the rat liver--new beneficial effect of lansoprazole. PLoS One, 9(5): e97419. https://doi.org/10.1371/journal.pone.0097419
YANAKA, A. 2018. Role of NRF2 in protection of the gastrointestinal tract against oxidative stress. Journal of clinical biochemistry and nutrition, 63(1): 18-25. https://doi.org/10.3164/jcbn.17-139
YUAN, J. S., REED, A., CHEN, F., and STEWART, C. N., Jr., 2006. Statistical analysis of real-time PCR data. BMC Bioinformatics, 7: 85. https://doi.org/10.1186/1471-2105-7-85
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