Effects of morin against tetracycline-induced liver injury in rats by biochemical and histopathological methods

Year 2025, Volume: 10 Issue: 3, 153 - 161, 31.12.2025

Serpil Aygörmez , Elif Dalkılınç , Nurhan Akaras , Şaban Maraşlı

https://doi.org/10.31797/vetbio.1696205

Abstract

In this study, the protective effect of morin against liver damage caused by Tetracycline (TET) was investigated. Twenty-eight female rats were divided into four groups: control, morin, TET, and TET+morin. TET (140 mg/kg) and morin (100 mg/kg) were administered orally for seven days. Liver enzymes, oxidative stress, and inflammation parameters were analyzed to determine liver tissue damage. In addition, histopathologic analysis was performed to detect tissue damage and structural changes. According to the data obtained from these analyses, TET increased aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities in liver tissue. TET administration increased malondialdehyde (MDA), decreased superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities and glutathione (GSH). Nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin 1β (IL-1β) expression levels were found to increase. Administration of morin together with TET decreased AST, ALT activities and MDA, NF-kB, TNF-α, IL-1β levels, and increased CAT, SOD, GSH, GPx. According to the data obtained, TET increases liver enzymes and the increase in these values triggers oxidative stress, and inflammation markers, indicating damage to the liver. Morin's supportive treatment was found to reduce liver damage by bringing these parameters closer to normal.

Keywords

Inflammation , morin , oxidative stress , rat , tetracycline

Ethical Statement

Ethical approval was obtained from Atatürk University Animal Experiments Local Ethics Committee (Approval No: 2025/01/21).

Supporting Institution

No

Project Number

No

Thanks

No

References

• Aebi, H. (1984). Catalase in vitro. Methods in Enzymology, 105, 121-126. https://doi.org/ 10.1016/S0076-6879(84)05016-3
• Aghaei, F., Arabzadeh, E., Hosseini, H. M., & Shirvani, H. (2023). Exercise training and probiotic lacticaseibacillus rhamnosus gg reduce tetracycline-ınduced liver oxidative stress and ınflammation in rats with hepatic steatosis. Probiotics and Antimicrobial Proteins, 15(5), 1393-1405. https://doi.org/10.1007/s12602-022-09994-6
• Akaras, N., Kandemir, F. M., Şimşek, H., Gür, C., & Aygörmez, S. (2023a). Antioxidant, antiinflammatory, and antiapoptotic effects of rutin in spleen toxicity induced by sodium valproate in rats. Türk Doğa ve Fen Dergisi, 12(2), 138-144. https://doi.org/10.46810/tdfd.1299663
• Akaras, N., Gur, C., Kucukler, S., & Kandemir, F. M. (2023b). Zingerone reduces sodium arsenite-induced nephrotoxicity by regulating oxidative stress, inflammation, apoptosis and histopathological changes. Chemico-Biological Interactions, 374, 110410. https://doi.org/10.1016/j.cbi.2023.110410
• Akaras, N., Kucukler, S., Gur, C., Ileriturk, M., & Kandemir, F. M. (2024a). Sinapic acid protects against lead acetate-induced lung toxicity by reducing oxidative stress, apoptosis, inflammation, and endoplasmic reticulum stress damage. Environmental Toxicology, 39(7), 3820-3832. https://doi.org/10.1002/tox.24255
• Akaras, N., Gür, C., Caglayan, C., & Kandemir, F. M. (2024b). Protective effects of naringin against oxaliplatin-induced testicular damage in rats: Involvement of oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and histopathology. The Iranian Journal of Basic Medical Sciences, 27(4), 466-474. https://doi.org/10.22038/IJBMS.2024.73824.16048
• Akarsu, S. A., Gür, C., Küçükler, S., Akaras, N., İleritürk, M., & Kandemir, F. M. (2024). Protective effects of syringic acid against oxidative damage, apoptosis, autophagy, inflammation, testicular histopathologic disorders, and impaired sperm quality in the testicular tissue of rats induced by mercuric chloride. Environmental Toxicology, 39(10), 4803-4814. https://doi.org/10.1002/tox.24395.
• Aksu, E. H., Kandemir, F. M., Yıldırım, S., Küçükler, S., Dörtbudak, M. B., Çağlayan, C., & Benzer, F. (2019). Palliative effect of curcumin on doxorubicin-induced testicular damage in male rats. Journal of Biochemical and Molecular Toxicology, 33(10), e22384. https://doi.org/10.1002/jbt.22384
• Amangelsin, Y., Semenova, Y., Dadar, M., Aljofan, M., & Bjørklund, G. (2023). The impact of tetracycline pollution on the aquatic environment and removal strategies. Antibiotics (Basel), 12(3), 440. https://doi.org/10.3390/antibiotics12030440
• Asha, K. K., Sankar, T. V., & Viswanathan Nair, P. G. (2007). Effect of tetracycline on pancreas and liver function of adult male albino rats. Journal of Pharmacy and Pharmacology, 59(9), 1241-1248. https://doi.org/10.1211/jpp.59.9.0008
• Aydin, M., Cevik, A., Kandemir, F. M., Yuksel, M., & Apaydin, A. M. (2009). Evaluation of hormonal change, biochemical parameters, and histopathological status of uterus in rats exposed to 50-Hz electromagnetic field. Toxicology and Industrial Health, 25(3), 153-158. https://doi.org/10.1177/0748233709102717
• Aygörmez, S., & Maraşli, Ş. (2024). Investigation of the effects of curcumin and piperine on cyclophosphamide-induced brain injury in rats. Journal of Biochemical and Molecular Toxicology, 38(7), e23760. https://doi.org/10.1002/jbt.23760
• Benzer, F., Kandemir, F. M. Ceribasi, S., Ozkaraca, M., Yildirim, N.C., & Ozan, S. T. (2012). Chemotherapeutic agent-induced nephrotoxicity in rabbits: protective role of grape seed extract. International Journal of Basic & Clinical Pharmacology, 8(1), 39-45. https://doi.org/10.3923/ijp.2012.39.45
• Caglayan, C., Kandemir, F. M., Darendelioğlu, E., Küçükler, S., & Ayna, A. (2021). Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms. Life Science, 281, 119730. https://doi.org/10.1016/j.lfs.2021.119730
• Cakmak, F., Kucukler, S., Gur, C., Comakli, S., Ileriturk, M., & Kandemir, F. M. (2023). Morin provides therapeutic effect by attenuating oxidative stress, inflammation, endoplasmic reticulum stress, autophagy, apoptosis, and oxidative DNA damage in testicular toxicity caused by ifosfamide in rats. The Iranian Journal of Basic Medical Sciences, 26(10), 1227-1236. https://doi.org/10.22038/IJBMS.2023.71702.15580
• Çelik H., Kucukler, S., Çomaklı, S., Özdemir, S., Caglayan, C., Yardım, A., & Kandemir, F. M. (2020). Morin attenuates ifosfamide-induced neurotoxicity in rats via suppression of oxidative stress, neuroinflammation and neuronal apoptosis. Neurotoxicology, 76, 126-137. 2020. https://doi.org/10.1016/j.neuro.2019.11.004
• Çomaklı, S., Kandemir, F. M., Küçükler, S., & Özdemir, S. (2022). Morin mitigates ifosfamide induced nephrotoxicity by regulation of NF-kappaB/p53 and Bcl-2 expression. Biotechnic & Histochemistry, 97(6), 423-432. https://doi.org/10.1080/10520295.2021.2021449.
• Darendelioglu, E., Caglayan, C., Küçükler, S., Bayav, İ., Kandemir, F. M., Ayna, A., & Sağ, S. (2025). 18β-glycyrrhetinic acid Mitigates bisphenol A-induced liver and renal damage: Inhibition of TNF-α/NF-κB/p38-MAPK, JAK1/STAT1 pathways, oxidative stress and apoptosis. Food and Chemical Toxicology, 196, 115218. https://doi.org/10.1016/j.fct.2024.115218
• Famurewa, A. C., Ekeleme-Egedigwe, C. A., Ogbu, P. N., Ajibare, A. J., Folawiyo, M. A., Obasi, D. O., & Narayanankutty, A. (2023). Morin hydrate downregulates inflammation‐mediated nitric oxide overproduction and potentiates antioxidant mechanism against anticancer drug doxorubicin oxidative hepatorenal toxicity in rats. Avicenna Journal of Phytomedicine, 13(5), 475. https://doi.org/ 10.22038/AJP.2023.22392
• Farombi, E. O., Ugwuezunmba, M. C., Ezenwadu, T. T., Oyeyemi, M. O., & Ekor, M. (2008). Tetracycline-induced reproductive toxicity in male rats: effects of vitamin C and N-acetylcysteine. Experimental and Toxicologic Pathology, 60(1), 77-85. https://doi.org/10.1016/j.etp.2008.02.002
• Genc, M., Kandemir, F. M., & Coban, O. (2019). Effects of in-ovo rutin injection to fertile Japanese quail (Coturnix Coturnix Japonica) egg on hatchability, embryonic death, hatchling weight, and hatchling liver oxidative and nitrosative stress. Brazilian Journal of Poultry Science, 21, eRBCA-2019. https://doi.org/ 10.1590/1806-9061-2018-0786
• Gencer, S., Gür, C., İleritürk, M., Küçükler, S., Akaras, N., Şimşek, H., & Kandemir, F. M. (2024). The ameliorative effect of carvacrol on sodium arsenite-induced hepatotoxicity in rats: Possible role of Nrf2/HO-1, RAGE/NLRP3, Bax/Bcl-2/Caspase-3, and Beclin-1 pathways. Journal of Biochemical and Molecular Toxicology, 38(10), e23863. https://doi.org/10.1002/jbt.23863
• Gur, C., Kandemir, F. M., Darendelioglu, E., Caglayan, C., Kucukler, S., Kandemir, O., & Ileriturk, M. (2021). Morin protects against acrylamide-induced neurotoxicity in rats: an investigation into different signal pathways. Environmental Science and Pollution Research, 28(36), 49808-49819. https://doi.org/10.1007/s11356-021-14049-4
• Gur, C., & Kandemir, F. M. (2023). Molecular and biochemical investigation of the protective effects of rutin against liver and kidney toxicity caused by malathion administration in a rat model. Environmental Toxicology, 38(3), 555-565. https://doi.org/10.1002/tox.23700
• Hosseini, H. M., Shirvani, H., Aghaei, F., Arabzadeh, E., & Hofmeister, M. (2022). Ameliorative effects of high intensity interval training and Lactobacillus rhamnosus GG protectagainst tetracycline-induced fatty liver in rats: a gene expression profiling comparative study. Journal Experimental and Clinical Sciences, 21, 991-1006. https://doi.org/10.17179/excli2022-4791
• Ileriturk, M., Kandemir, O., Akaras, N., Simsek, H., Genc, A., & Kandemir, F. M. (2023). Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress. Reproductive Toxicology, 118, 108369. https://doi.org/10.1016/j.reprotox.2023.108369
• Kandemir, F. M., Yıldırım, S., Kucukler, S., Caglayan, C., Darendelioğlu, E., & Dortbudak, M. B. (2020). Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food and Chemical Toxicology, 138, 111190. https://doi.org/10.1016/j.fct.2020.111190
• Kandemir, F. M., Ileriturk, M., & Gur, C. (2022). Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy. Molecular Biology Reports, 49(7), 6063-6074. https://doi.org/10.1007/s11033-022-07395-0
• Kankılıç, N. A., Şimşek, H., Akaras, N., Gür, C., Küçükler, S., İleritürk, M., Gencer, S., & Kandemir, F. M. (2024a). The ameliorative effects of chrysin on bortezomib-induced nephrotoxicity in rats: Reduces oxidative stress, endoplasmic reticulum stress, inflammation damage, apoptotic and autophagic death. Food and Chemical Toxicology, 190, 114791. https://doi.org/10.1016/j.fct.2024.114791
• Kankılıç, N. A., Küçükler, S., Gür, C., Akarsu, S. A., Akaras, N., Şimşek, H., İleritürk, M., & Kandemir, F. M. (2024b). Naringin protects against paclitaxel-induced toxicity in rat testicular tissues by regulating genes in pro-inflammatory cytokines, oxidative stress, apoptosis, and JNK/MAPK signaling pathways. Journal of Biochemical and Molecular Toxicology, 38(7), e23751. https://doi.org/10.1002/jbt.23751
• Kankılıç, N. A., Şimşek, H., Akaras, N., Gür, C., İleritürk, M., Küçükler, S., Akarsu, S. A., & Kandemir, F. M. (2024c). Protective effects of naringin on colistin-induced damage in rat testicular tissue: Modulating the levels of Nrf-2/HO-1, AKT-2/FOXO1A, Bax/Bcl2/Caspase-3, and Beclin-1/LC3A/LC3B signaling pathways. Journal of Biochemical and Molecular Toxicology, 38(2), e23643. https://doi.org/10.1002/jbt.23643
• Karaboğa, M., & Avcı, H. (2023). Investigation of the effect of sodium selenite on metallothioneine expression in the liver and kidney in experimental cyclophosphamide toxicity. Journal of Advances in VetBio Science and Techniques, 8(2), 101-111. https://doi.org/ 10.31797/vetbio.1285594
• Karaca, O., Şimşek, H., Akaras, N., Gür, C., İleritürk, M., Kandemir, Ö., Küçükler, S., Karaca, Ş. Ö., & Kandemir. F. M. (2025a). Potent ameliorative effects of rosmarinic acid on tramadol-ınduced neurotoxicity in the brain and hippocampus; by suppressing oxidative stress, apoptosis, er stress, and regulating cognitive functions. Molecular Neurobiology, 7, https://doi.org/10.1007/s12035-025-04892-8
• Karaca, O., Akaras, N., Şimşek, H., Gür, C., İleritürk, M., Küçükler, S., Gencer, S., & Kandemir, F. M. (2025b). Therapeutic potential of rosmarinic acid in tramadol-induced hepatorenal toxicity: Modulation of oxidative stress, inflammation, RAGE/NLRP3, ER stress, apoptosis, and tissue functions parameters. Food and Chemical Toxicology, 197, 115275. https://doi.org/10.1016/j.fct.2025.115275
• Kızıl, H. E., Caglayan, C., Darendelioğlu, E., Ayna, A., Gür, C., Kandemir, F. M., & Küçükler, S. (2023). Morin ameliorates methotrexate-induced hepatotoxicity via targeting Nrf2/HO-1 and Bax/Bcl2/Caspase-3 signaling pathways. Molecular Biology Reports, 50(4), 3479-3488. https://doi.org/10.1007/s11033-023-08286-8
• Kuzu, M., Kandemir, F. M., Yildirim, S., Kucukler, S., Caglayan, C., & Turk, E. (2018). Morin attenuates doxorubicin-induced heart and brain damage by reducing oxidative stress, inflammation and apoptosis. Biomedicine & Pharmacotherapy, 106, 443-453. https://doi.org/10.1016/j.biopha.2018.06.161
• Kuzu, M., Yıldırım, S., Kandemir, F. M., Küçükler, S., Çağlayan, C., Türk, E., & Dörtbudak, M. B. (2019). Protective effect of morin on doxorubicin-induced hepatorenal toxicity in rats. Chemico-Biological Interactions, 308, 89-100. https://doi.org/10.1016/j.cbi.2019.05.017
• Küçükler, S., Caglayan, C., Darendelioğlu, E., & Kandemir, F. M. (2020). Morin attenuates acrylamide-induced testicular toxicity in rats by regulating the NF-κB, Bax/Bcl-2 and PI3K/Akt/mTOR signaling pathways. Life Sciences, 261, 118301. https://doi.org/10.1016/j.lfs.2020.118301
• Küçükler, S., Caglayan, C., Özdemir, S., Çomaklı, S., & Kandemir, F. M. (2024). Hesperidin counteracts chlorpyrifos-induced neurotoxicity by regulating oxidative stress, inflammation, and apoptosis in rats. Metabolic Brain Disease, 39(4), 509-522. https://doi.org/10.1007/s11011-023-01339-8
• Lawrence, R.A., & Burk, R.F. (1976). Glutathione peroxidase activity in selenium-deficient rat liver. Biochemical and Biophysical Research Communications, 71(4), 952-958. https://doi.org/10.1016/0006-291x(76)90747-6
• Leichtweis, J., Vieira, Y., Welter, N., Silvestri, S., Dotto, G. L., & Carissimi, E. (2022). A review of the occurrence, disposal, determination, toxicity and remediation technologies of the tetracycline antibiotic. Process Safety and Environmental Protection, 160, 25-40. https://doi.org/10.1016/j.psep.2022.01.085
• Liu, D., Lu, L., Wang, M., Hussain, B., Tian, S., Luo, W., Zhou, J., & Yang, X. (2019). Tetracycline uptake by pak choi grown on contaminated soils and its toxicity in human liver cell line HL-7702. Environmental Pollution, 253, 312-321. https://doi.org/10.1016/j.envpol.2019.06.086
• Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25(4), 402-408. https://doi.org/10.1006/meth.2001.1262.
• Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1), 265-275.
• Mesgari Abbasi, M., Hassanalilou, T., Khordadmehr, M., Mohammadzadeh Vardin, A., Behroozi Kohlan, A., & Khalili, L. (2020). Effects of Cornus mas fruit hydro-methanolic extract on liver antioxidants and histopathologic changes induced by cisplatin in rats. Indian Journal of Clinical Biochemistry, 35(2), 218-224. https://doi.org/10.1007/s12291-018-0809-z
• Özdemir, S., Kucukler, S., Çomaklı, S., & Kandemir, F. M. (2022). The protective effect of Morin against ifosfamide-induced acute liver injury in rats associated with the inhibition of DNA damage and apoptosis. Drug and Chemical Toxicology, 45(3), 1308-1317. https://doi.org/10.1080/01480545.2020.1822390
• Öztürk, A. B., Akaras, N., Şimşek, H., & Kandemir, F. M. (2025). Investigation of the effects of silymarin on ovarian ischemia reperfusion via nrf-2/ho-1/nqo1, ki-67 and wnt signaling pathways. Journal of Biochemical and Molecular Toxicology, 39(1), e70138. https://doi.org/10.1002/jbt.70138
• Placer, Z. A., Cushman, L. L., & Johnson, B. C. (1966). Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Analytical Biochemistry, 16(2), 359-364. https://doi.org/10.1016/0003-2697(66)90167-9
• Reyes, A. G., Renato A. Dela Pena, R. A. D., Sula, L. F. I., & Banares, A. B. (2016). Histoprotective potentials of ethanol leaf extract of balakat tree (Ziziphus talanai (blanco) merr.) against tetracycline-induced hepatotoxicity and reprotoxicity in male mice (Mus musculus L.). International Journal of Pharmacology and Toxicology, 4(2), 96-104. https://doi.org/10.14419/ijpt.v4i2.6169
• Rusu, A., & Buta, E. L. (2021). The development of third-generation tetracycline antibiotics and new perspectives. Pharmaceutics, 13(12), 2085. https://doi.org/10.3390/pharmaceutics13122085
• Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analytical Biochemistry, 25(1), 192-205. https://doi.org/10.1016/0003-2697(68)90092-4
• Shabana, M. B., Ibrahim, H. M., Khadre, S. E. M., & Elemam, M. G. (2012). Influence of rifampicin and tetracycline administration on some biochemical and histological parameters in albino rats. The Journal of Basic & Applied Zoology, 65, 299-308, https://doi.org/ 10.1016/j.jobaz.2012.10.009
• Shen, C., Meng, Q., Schmelzer, E., & Bader, A. (2009). Gel entrapment culture of rat hepatocytes for investigation of tetracycline-induced toxicity. Toxicology and Applied Pharmacology, 238(2), 178-187. https://doi.org/10.1016/j.taap.2009.05.014
• Sun, Y., Oberleyi L. W., & Li, Y. (1988). A simple method for clinical assay of superoxide dismutase. Clinical Chemistry, 34(3), 497-500. https://doi.org/10.1093/clinchem/34.3.497
• Şimşek, H., Akaras, N., Gür, C., Küçükler, S., & Kandemir, F. M. (2023). Beneficial effects of Chrysin on Cadmium‐induced nephrotoxicity in rats: Modulating the levels of Nrf2/HO‐1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways. Gene, 875, 147502. https://doi.org/10.1016/j.gene.2023.147502
• Şimşek, H., Gür, C., Küçükler, S., İleritürk, M., Akaras, N., Öz, M., & Kandemir, F. M. (2024). Carvacrol reduces mercuric chloride-ınduced testicular toxicity by regulating oxidative stress, ınflammation, apoptosis, autophagy, and histopathological changes. Biological Trace Element Research, 202(10), 4605-4617. https://doi.org/10.1007/s12011-023-04022-2
• Şimşek, H., Akaras, N., Gür, C., Küçükler, S., İleritürk, M., & Kandemir, F. M. (2025). Ameliorative effect of morin on diclofenac-induced testicular toxicity in rats: An investigation into different signal pathways. Iranian Journal of Basic Medical Sciences, 28(4), 507-515. https://doi.org/10.22038/ijbms.2025.79735.17270
• Tanvir, E. M., Hasan, M. A., Nayan, S. I., Islam, T., Ahmed, T., Hossen, M. S., Perveen, R., Rahman, S., Afroz, R., Afroz, R., & Chowdhury, M. Z. C. (2019). Ameliorative effects of ethanolic constituents of Bangladeshi propolis against tetracycline-induced hepatic and renal toxicity in rats. Journal of Food Biochemistry, 43(8), e12958. https://doi.org/10.1111/jfbc.12958
• Tuncer, S. Ç., Gur, C., Kucukler, S., Akarsu, S. A., & Kandemir, F. M. (2024). Effects of zingerone on rat induced testicular toxicity by sodium arsenite via oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and autophagy pathways. The Iranian Journal of Basic Medical Sciences, 27(5), 603-610. https://doi.org/10.22038/IJBMS.2024.73342.15934
• Varışlı, B., Caglayan, C., Kandemir., F. M., Gür, C., Bayav, İ., & Genç, A. (2022). The impact of Nrf2/HO-1, caspase-3/Bax/Bcl2 and ATF6/IRE1/PERK/GRP78 signaling pathways in the ameliorative effects of morin against methotrexate-induced testicular toxicity in rats. Molecular Biology Reports, 49(10), 9641-9649. https://doi.org/10.1007/s11033-022-07873-5
• Yıldız, M. O., Çelik, H., Caglayan, C., Kandemir, F. M., Gür, C., Bayav, İ., Aydın Genç, A., & Kandemir, Ö. (2022). Neuromodulatory effects of hesperidin against sodium fluoride-induced neurotoxicity in rats: Involvement of neuroinflammation, endoplasmic reticulum stress, apoptosis and autophagy. Neurotoxicology, 90, 197-204. https://doi.org/10.1016/j.neuro.2022.04.002.
• Yılmaz, S., Küçükler, S., Şimşek, H., Aygörmez, S., & Kandemir, F. M. (2024a). Naringin protects against colistin-induced sciatic nerve damage by reducing oxidative stress, apoptosis and inflammation damage. Journal of Experimental and Clinical Medicine, 41(1), 53-59. https://doi.org/10.52142/omujecm.41.1.9
• Yilmaz, S., Gur, C., Kucukler, S., Akaras, N., & Kandemir, F. M. (2024b). Zingerone attenuates sciatic nerve damage caused by sodium arsenite by inhibiting NF-κB, caspase-3, and ATF-6/CHOP pathways and activating the Akt2/FOXO1 pathway. The Iranian Journal of Basic Medical Sciences, 27(4), 485-491. https://doi.org/10.22038/IJBMS.2023.74088.16094