Sodyum Hidrosülfür, Sıçanlarda Vankomisin Kaynaklı Karaciğer Hasarını Azaltır: Redoks Dengesi, Enflamasyon ve Hücre Ölümünün Rolleri

Öz

Vankomisin (VAN), şiddetli Gram-pozitif enfeksiyonların tedavisinde yaygın olarak tercih edilen bir glikopeptid antibiyotiktir. Ancak yüksek sistemik maruziyet, hepatotoksisiteye yol açarak ilacın klinik kullanımını sınırlandırabilmektedir. Hidrojen sülfürün (H₂S) suda çözünebilen bir donörü olan sodyum hidrosülfür (NaHS), güçlü antioksidan, anti-inflamatuvar, anti-apoptotik ve sitoprotektif özelliklere sahiptir. Bu çalışmada, NaHS'nin sıçanlarda VAN kaynaklı karaciğer hasarına karşı olası hepatoprotektif etkileri araştırılmıştır. Çalışmada otuz erişkin erkek Sprague–Dawley sıçan rastgele beş gruba ayrılmıştır (n = 6): Kontrol, NaHS (56 µmol/kg), VAN (200 mg/kg), VAN + NaHS28 (28 µmol/kg) ve VAN + NaHS56 (56 µmol/kg). Vankomisin yedi gün boyunca günde bir kez intraperitoneal olarak uygulanmış, NaHS ise her VAN uygulamasından 30 dakika sonra enjekte edilmiştir. Karaciğer hasarı, serum alanin aminotransferaz (ALT) ve aspartat aminotransferaz (AST) aktiviteleri ölçülerek değerlendirilmiştir. Oksidatif stres; karaciğer dokusunda malondialdehit (MDA) düzeyi ile birlikte glutatyon (GSH) içeriği ve antioksidan enzimler olan süperoksit dismutaz (SOD), katalaz (KAT) ve glutatyon peroksidaz (GPx) aktiviteleri belirlenerek değerlendirilmiştir. İnflamatuvar yanıt, nükleer faktör-kappa B (NF-κB) ve tümör nekroz faktörü-alfa (TNF-α) düzeyleri ile incelenirken; apoptoz, otofaji ve oksidatif DNA hasarı sırasıyla kaspaz-3, beklin-1 ve 8-hidroksi-2′-deoksiguanozin (8-OHdG) belirteçleri kullanılarak değerlendirilmiştir. Histopatolojik değişiklikler hematoksilen-eozin ile boyanmış karaciğer kesitlerinde incelenmiştir. Vankomisin uygulaması, serum ALT ve AST aktiviteleri ile karaciğer dokusunda MDA, NF-κB, TNF-α, kaspaz-3, beklin-1 ve 8-OHdG düzeylerini anlamlı düzeyde artırırken; GSH içeriği ile GPx, SOD ve KAT aktivitelerini belirgin şekilde azaltmıştır (p <0,001). NaHS uygulaması, her iki dozda da VAN'ın neden olduğu biyokimyasal ve histopatolojik değişiklikleri anlamlı ölçüde azaltmıştır (p <0,001). Histopatolojik bulgular biyokimyasal sonuçları desteklemiştir. Sonuç olarak NaHS, oksidatif stresi, inflamasyonu, apoptozu, otofajiyi ve oksidatif DNA hasarını baskılayarak, aynı zamanda karaciğerin antioksidan savunma sistemini koruyarak vankomisine bağlı hepatotoksisiteyi doza bağımlı şekilde hafifletmiştir. Bu bulgular, NaHS gibi H₂S donörlerinin vankomisine bağlı karaciğer hasarının önlenmesinde umut verici terapötik adaylar olabileceğini göstermektedir.

Anahtar Kelimeler

• Karaciğer
• Oksidatif stres
• Sodyum hidrosülfür
• Vankomisin.

Etik Beyan

Etik Komite Onayı: Araştırmanın etik onayı Erzincan Binali Yıldırım Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu'ndan (HADYEK) alınmıştır (onay no: E-85748827-050.04-549830; oturum tarihi: 21.05.2026; oturum no: 2026/05).

Teşekkür

Yazarlar, bu çalışmanın biyokimyasal analizlerine yaptığı değerli katkı ve desteği için Prof. Dr. Fatih Mehmet Kandemir’e içten teşekkürlerini sunar.

Sodium Hydrosulfide Attenuates Vancomycin-Related Liver Damage in Rats: Roles of Redox Balance, Inflammation, and Cell Death

Öz

Vancomycin (VAN), a glycopeptide antibiotic used to treat severe Gram-positive infections, may cause hepatotoxicity at high systemic exposure, limiting its clinical use. Sodium hydrosulfide (NaHS), a water-soluble hydrogen sulfide (H₂S) donor, possesses antioxidant, anti-inflammatory, anti-apoptotic, and cytoprotective properties. This study investigated the hepatoprotective effects of NaHS against VAN-induced liver injury in rats. Thirty adult male Sprague–Dawley rats were randomly assigned to five groups (n = 6): Control, NaHS (56 µmol/kg), VAN (200 mg/kg), VAN + NaHS28 (28 µmol/kg), and VAN + NaHS56 (56 µmol/kg). Hepatic injury was evaluated by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Oxidative stress was assessed by hepatic malondialdehyde (MDA), glutathione (GSH), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Inflammation, apoptosis, autophagy, and oxidative DNA damage were evaluated by measuring nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), caspase-3, beclin-1, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), respectively. Histopathological examination was also performed. VAN significantly increased serum ALT and AST activities and hepatic MDA, NF-κB, TNF-α, caspase-3, beclin-1, and 8-OHdG levels, while reducing GSH content and GPx, SOD, and CAT activities (p < .001). NaHS treatment significantly attenuated these biochemical and histopathological alterations at both doses. In conclusion, NaHS protected against VAN-induced hepatotoxicity by reducing oxidative stress, inflammation, apoptosis, and oxidative DNA damage while preserving antioxidant defenses. These findings suggest that H₂S donors such as NaHS may represent promising therapeutic agents for preventing vancomycin-induced liver injury.

Anahtar Kelimeler

• Liver
• Oxidative stress
• Sodium hydrosulfide
• Vancomycin.

Etik Beyan

Ethics Committee Approval: Ethical approval for the study was obtained from the Erzincan Binali Yıldırım University Animal Experiments Local Ethics Committee (HADYEK) (approval no: E-85748827-050.04-549830; session date: 21.05.2026; session no: 2026/05).

Teşekkür

The authors would like to sincerely thank Prof. Dr. Fatih Mehmet Kandemir for his valuable support and contribution to the biochemical analyses of this study.

Kaynakça

1. Aebi, H. (1984). Catalase in vitro. Methods in Enzymology, 105, 121–126. https://doi.org/10.1016/S0076-6879(84)05016-3
2. Aksakal, E., Akaras, N., Tanboga, I. H., Kurt, M., Halici, Z., Odabasoglu, F., & Unal, B. (2011). Relationship between oxidative stress and cardiomyopathic changes in ovariectomized rats. Cardiology, 119(4), 235-241. https://doi.org/10.1159/000333003
3. Akaras, N., Bal, T., Atilay, H., Selli, J., & Halici, M. B. (2017). Protective effects of agomelatine on testicular damage caused by bortezomib. Biotechnic & Histochemistry, 92(8), 552-559. https://doi.org/10.1080/10520295.2017.1350748
4. Akaras, N., Abuc, O. O., Koc, K., Bal, T., Geyikoglu, F., Atilay, H., Erol, H. S., Yigit, S., & Gul, M. (2020). (1 → 3)-β-d-glucan enhances the toxicity induced by Bortezomib in rat testis. Journal of Food Biochemistry, 44(3), 13155. https://doi.org/10.1111/jfbc.13155
5. Akaras, N., Gür, C., Şimşek, H., & Tuncer, S. Ç. (2023). Effects of quercetin on cypermethrin-induced stomach injury: The role of oxidative stress, inflammation, and apoptosis. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, 12(2), 556-566. https://doi.org/10.37989/gumussagbil.1225539
6. 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
7. Akaras, N., Kandemir, Ö., & Şimşek, H. (2024b). Carvacrol ameliorates cisplatin-induced cardiotoxicity by regulating notch/hes1 signaling pathway, oxidative stress and cell death in rat cardiac tissue. Turkish Journal of Nature and Science, 13(4), 180-191. https://doi.org/10.46810/tdfd.1564047
8. Akaras, N., Şimşek, H., Gür, C., Küçükler, S., İleritürk, M., & Kandemir, F. M. (2025). Morin attenuates diclofenac-induced hepatocellular death injury via Nrf2/Ho-1/NQO1, Beclin-1/LC3A/LC3B and p53/Bax/caspase signalling pathways. Journal Of Biochemical and Molecular Toxicology, 39(7), 70372. https://doi.org/10.1002/jbt.70372

9. Akarsu, S. A., Gür, C., Küçükler, S., Akaras, N., İleritürk, M., & Kandemir, F. M. (2024a). 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
10. Akarsu, S. A., İleritürk, M., Küçükler, S., Akaras, N., Gür, C., &, Kandemir, F. M. (2024b). Ameliorative effects of sinapic acid against vancomycin-induced testicular oxidative damage, apoptosis, inflammation, testicular histopathologic disorders and decreased epididymal sperm quality. Reproductive Toxicology, 129, 108666. https://doi.org/10.1016/j.reprotox.2024.108666
11. Aksu, E. H., Kandemir, F. M., & Küçükler, S. (2021). Ameliorative effect of hesperidin on streptozotocin‐diabetes mellitus‐induced testicular DNA damage and sperm quality degradation in Sprague–Dawley rats. Journal of Food Biochemistry, 45(10), 13938. https://doi.org/10.1111/jfbc.13938
12. Alshehri, F. S., & Alorfi, N. M. (2023). Protective role of resveratrol against VCM-induced hepatotoxicity in male Wistar rats. Frontiers in Pharmacology, 14, 1130670. https://doi.org/10.3389/fphar.2023.1130670
13. 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
14. Bos, E. M., Snijder, P. M., Jekel, H., Weij, M., Leemans, J. C., van Dijk, M. C., Hillebrands, J. L., Lisman, T., van Goor, H., & Leuvenink, H. G. (2012). Beneficial effects of gaseous hydrogen sulfide in hepatic ischemia/reperfusion injury. Transplant International, 25(8), 897–908. https://doi.org/10.1111/j.1432-2277.2012.01514.x
15. Calvert, J. W., Jha, S., Gundewar, S., Elrod, J. W., Ramachandran, A., Pattillo, C. B., Kevil, C. G., & Lefer, D. J. (2009). Hydrogen sulfide mediates cardioprotection through Nrf2 signaling. Circulation Research, 105(4), 365–374. https://doi.org/10.1161/CIRCRESAHA.109.199919
16. Çağlayan, C., Taslimi, P., Demir, Y., Küçükler, S., Kandemir, F. M., & Gulçin, İ. (2019). The effects of zingerone against vancomycin-induced lung, liver, kidney and testis toxicity in rats: The behavior of some metabolic enzymes. Journal of Biochemical and Molecular Toxicology, 33(10), e22381. https://doi.org/10.1002/jbt.22381
17. Caglayan, C., Kandemir, F. M., Ayna, A., Gür, C., Küçükler, S., & Darendelioğlu, E. (2022). Neuroprotective effects of 18β-glycyrrhetinic acid against bisphenol A-induced neurotoxicity in rats: involvement of neuronal apoptosis, endoplasmic reticulum stress and JAK1/STAT1 signaling pathway. Metabolic Brain Disease, 37(6), 1931-1940. https://doi.org/10.1007/s11011-022-01027-z
18. Çelik, H., Kucukler, S., Çomaklı, S., Caglayan, C., Özdemir, S., Yardım, A., Karaman, M., & Kandemir, F. M. (2020). Neuroprotective effect of chrysin on isoniazid-induced neurotoxicity via suppression of oxidative stress, inflammation and apoptosis in rats. Neurotoxicology, 81, 197-208. https://doi.org/10.1016/j.neuro.2020.10.009
19. Ekinci Akdemir, F. N., Yildirim, S., Kandemir, F. M., Aksu, E. H., Guler, M. C., Kiziltunc Ozmen, H., Kucukler, S., & Eser, G. (2019). The antiapoptotic and antioxidant effects of eugenol against cisplatin‐induced testicular damage in the experimental model. Andrologia, 51(9), 13353. https://doi.org/10.1111/and.13353
20. Ekinci Akdemir, F. N., Yildirim, S., Kandemir, F. M., Tanyeli, A., Küçükler, S., & Bahaeddin Dortbudak, M. (2021). Protective effects of gallic acid on doxorubicin-induced cardiotoxicity; an experimantal study. Archives of Physiology and Biochemistry, 127(3),258-265. https://doi.org/10.1080/13813455.2019.1630652
21. Elgendy, S. A., Soliman, M. M., Shukry, M., Mohammed, L. A., Ibrahim, M. H., Abdelhady Mohammed, D., Mahmood Fawzey Atta, M., Althobaiti, S. A., Abozeid, E. A., & Elnoury, H. A. (2026). Exploring the protective impacts of rhodiola rosea extract against vancomycin-induced hepatic and renal toxicity through the activation of Nrf2/HO-1 and MAPK kinases, inhibition of NF-κB and TGF-β1 signaling pathways, role of apoptosis and inflammation associated-markers. Drug and Chemical Toxicology, 1–17. https://doi.org/10.1080/01480545.2026.2700298
22. Erişir, M., Benzer, F., & Kandemir, F. M. (2009). Changes in the rate of lipid peroxidation in plasma and selected blood antioxidants before and during pregnancy in ewes. Acta Veterinaria Brno, 78(2), 237-242. https://doi.org/10.2754/avb200978020237
23. Fouad, A. A., Hafez, H. M., & Hamouda, A. A. H. (2020). Hydrogen sulfide modulates IL-6/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity. Human & Experimental Toxicology, 39(1), 77–85. https://doi.org/10.1177/0960327119877437
24. Gencer, S., Şimşek, H., Akaras, N., İleritürk, M., Gür, C., Küçükler, S., Kankılıç, N. A., & Kandemir, F. M. (2025). Hesperidin ameliorates vancomycin-induced kidney injury via multipathway modulation: Nrf-2/HO-1, Caspase-3/Bax/Bcl-2, ATF-4, KIM-1 and improved renal tissue function. Biochemical Pharmacology, 240, 117131. https://doi.org/10.1016/j.bcp.2025.117131
25. 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
26. Gur, C., Ileriturk, M., Akaras, N., & Kandemir, F. M. (2026). Sinapic acid attenuates vancomycin-induced hepatotoxicity in rats via modulation of ER stress (CHOP, IRE1, ATF-6, PERK), apoptotic pathways (caspase-3, Bax/Bcl-2, Apaf-1, cytochrome-c), and antioxidant defenses. Tissue & Cell, 99, 103255. https://doi.org/10.1016/j.tice.2025.103255
27. Güzel Kara, S., Uçkun Şahinoğulları, Z., Canacankatan, N., Antmen, Ş. E., Kibar, D., & Bayrak, G. (2019). The ameliorating effect of silymarin against vancomycin-induced apoptosis and inflammation in rat liver. Journal of Research in Pharmacy, 23(4), 719–728.
28. Ibrahim, S. A., Abdel-Gaber, S. A., Ibrahim, M. A., Amin, E. F., Mohammed, R. K., & Abdelrahman, A. M. (2022). Nitric oxide modulation as a potential molecular mechanism underlying the protective role of NaHS in liver ischemia reperfusion injury. Current Molecular Pharmacology, 15(4), 676–682. https://doi.org/10.2174/1874467214666210909154609
29. Kandemir, F. M., Yildirim, S., Kucukler, S., Caglayan, C., Mahamadu, A., & Dortbudak, M. B. (2018). Therapeutic efficacy of zingerone against vancomycin-induced oxidative stress, inflammation, apoptosis and aquaporin 1 permeability in rat kidney. Biomedicine & Pharmacotherapy, 105, 981–991. https://doi.org/10.1016/j.biopha.2018.06.048
30. Kandemir, Ö., Küçükler, S., Özdemir, S., Dalkılıç, E., Sağ, S., Caglayan, C., & Kandemir, F. M. (2025). Protective effects of quercetin against vincristine‐induced nephrotoxicity via modulation of oxidative stress, inflammation, and apoptosis in rats. Journal of Biochemical and Molecular Toxicology, 39(9), e70516. https://doi.org/10.1002/jbt.70516
31. Keleş, O. N., Can, S., Cigsar, G., Colak, S., Erol, H.S., Akaras, N., Erdemci, B., Bilgin, B.C., Can, I., Unal, B., & Halici, M.B. (2014). Hepatoprotective effects of B-1, 3-(D)-glucan on bortezomib-induced liver damage in rats. Kafkas Universitesi Veteriner Fakultesi Dergisi, 20(6), 929–938. https://doi.org/10.9775/kvfd.2014.11413
32. Keshari, A. C., Thitame, S. N., Aher, A. A., & Keshari, U. C. (2025). Drug-induced liver injury: Mechanisms, diagnosis, and management: A review. Journal of Pharmacy and Bioallied Sciences, 17(Suppl 1), 55–58. https://doi.org/10.4103/jpbs.jpbs_568_25
33. Küçükler, S., Kandemir, F. M., Özdemir, S., Çomaklı, S., & Caglayan, C. (2021). Protective effects of rutin against deltamethrin-induced hepatotoxicity and nephrotoxicity in rats via regulation of oxidative stress, inflammation, and apoptosis. Environmental Science and Pollution Research, 28(44), 62975-62990. https://doi.org/10.1007/s11356-021-15190-w
34. Küçükler, S., Kandemir, F. M., & Yıldırım, S. (2022). Protective effect of chrysin on indomethacin induced gastric ulcer in rats: role of multi-pathway regulation. Biotechnic & Histochemistry, 97(7), 490-503. https://doi.org/10.1080/10520295.2021.2014569
35. 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
36. 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. https://doi.org/10.1016/S0021-9258(19)52451-6
37. Oğuz Kabayel, R., Akaras, N., Kandemir, Ö., Şimşek, H., & Kandemir, F. M. (2025). Histopathological and biochemical investigation of the effects of rutin on diclofenac-induced renal toxicity in rats. Journal of Laboratory Animal Science and Practices, 5(2), 81-91. https://doi.org/10.62425/jlasp.1581664
38. 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
39. Placer, Z. A., Cushman, L. L., & Johnson, B. C. (1966). Estimation of product of lipid peroxidation (malonyldialdehyde) in biochemical systems. Analytical Biochemistry, 16(2), 359–364. https://doi.org/10.1016/0003-2697(66)90167-9
40. Sahin, M., Cam, H., Olgar, S., Tunc, S. E., Arslan, C., Uz, E., & Yilmaz, H. R. (2006). Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver. Molecular and Cellular Biochemistry, 291(1–2), 155–160. https://doi.org/10.1007/s11010-006-9209-4
41. Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analytical Biochemistry, 25, 192–205. https://doi.org/10.1016/0003-2697(68)90092-4
42. Selli, J., Unal, D., Mercantepe, F., Akaras, N., Kabayel, R., Unal, B., & Atilay, H. (2016). Protective effects of beta glucan in brain tissues of post-menopausal rats: a histochemical and ultra-structural study. Gynecological Endocrinology, 32(3), 234-239. https://doi.org/10.3109/09513590.2015.1110139
43. Sen, U., Pushpakumar, S. B., Amin, M. A., & Tyagi, S. C. (2014). Homocysteine in renovascular complications: Hydrogen sulfide is a modulator and plausible anaerobic ATP generator. Nitric Oxide, 41, 27–37. https://doi.org/10.1016/j.niox.2014.06.006
44. Sun, Y., Oberley, L. W., & Li, Y. (1988). A simple method for clinical assay of superoxide dismutase. Clinical Chemistry, 34(3), 497–500.
45. Tuncer, S. Ç., Akarsu, S. A., Küçükler, S., Gür, C., & Kandemir, F. M. (2023). Effects of sinapic acid on lead acetate‐induced oxidative stress, apoptosis and inflammation in testicular tissue. Environmental Toxicology, 38(11), 2656-2667. https://doi.org/10.1002/tox.23900
46. Uçkun Şahinoğulları, Z., Güzel, S., Canacankatan, N., Yalaza, C., Kibar, D., & Bayrak, G. (2021). Naringenin reduces hepatic inflammation and apoptosis induced by vancomycin in rats. Clinical and Experimental Health Sciences, 11(2), 191–198. https://doi.org/10.33808/clinexphealthsci.741916
47. Valavanidis, A., Vlachogianni, T., & Fiotakis, C. (2009). 8-Hydroxy-2′-deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. Journal of Environmental Science and Health, Part C, 27(2), 120–139. https://doi.org/10.1080/10590500902885684
48. 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
49. Villanueva-Paz, M., Morán, L., López-Alcántara, N., Freixo, C., Andrade, R. J., Lucena, M. I., & Cubero, F. J. (2021). Oxidative stress in drug-induced liver injury (DILI): From mechanisms to biomarkers for use in clinical practice. Antioxidants, 10(3), 390. https://doi.org/10.3390/antiox10030390
50. Wu, J., & Zhou, Y. (2024). Case analysis of hepatotoxicity caused by vancomycin. Journal of Medical Case Reports, 18(1), 267. https://doi.org/10.1186/s13256-024-04574-4
51. Yardim, A., Gur, C., Comakli, S., Ozdemir, S., Kucukler, S., Celik, H., & Kandemir, F. M. (2022). Investigation of the effects of berberine on bortezomib-induced sciatic nerve and spinal cord damage in rats through pathways involved in oxidative stress and neuro-inflammation. Neurotoxicology, 89, 127-139. https://doi.org/10.1016/j.neuro.2022.01.011
52. Yilmaz, S., Gur, C., Kucukler, S., Akaras, N., & Kandemir, F. M. (2024). 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. Iranian Journal of Basic Medical Sciences, 27(4), 485. https://doi.org/10.22038/IJBMS.2023.74088.16094
53. Zheng, J., Zhao, T., Yuan, Y., Hu, N., & Tang, X. (2015). Hydrogen sulfide (H2S) attenuates uranium-induced acute nephrotoxicity through oxidative stress and inflammatory response via Nrf2-NF-κB pathways. Chemico-Biological Interactions, 242, 353–362. https://doi.org/10.1016/j.cbi.2015.10.021