Oroxylum indicum root bark extract mitigates hepato-renal damage induced by acetaminophen and cisplatin
-
Seema Menon
Abstract
Oroxylum indicum is an important Ayurvedic plant from the “Dasamoola” group, traditionally used as a detoxifying agent. This study evaluates the protective effects of the root bark methanol extract of O. indicum (ORX) against acetaminophen-induced hepatotoxicity and cisplatin-induced nephrotoxicity in rats. The doses of ORX used in the study were selected based on the previous toxicity analysis (200 mg/kg and 400 mg/kg doses). Acetaminophen administration increased serum liver function markers (AST, ALT, ALP, bilirubin), while ORX and silymarin treatments significantly reduced these levels (p < 0.01). ORX administration also reversed the acetaminophen-induced depletion in hepatic redox balance as indicated in terms of SOD, GPx, GSH and lipid peroxidation. Corroborating these, the changes in the hepatic normal architecture induced by acetaminophen were also reversed by the pre-treatment with ORX. Similarly, the cisplatin administration resulted in strong myelosuppression and nephrotoxicity. In cisplatin-exposed rats, renal oxidative stress markers worsened, and serum renal function parameters were elevated. On the contrary, the pre-treatment with ORX alleviated the cisplatin-induced myelosuppression and redox imbalance in the renal tissues; further, it also restored the renal histology to near normal. Overall, O. indicum root bark extract effectively mitigated drug-induced liver and kidney damage, likely through redox balance restoration.
Acknowledgments
SM acknowledge Council of Scientific and Industrial Research, Government of India for the financial support in the form of Senior Research Fellowship (09/869 (0008)/2011-EMR-I).
-
Research ethics: All authors stick to the ethics regulations. All animal experiments have been approved by IAEC (Approval No. ACRC/IAEC/15/02-(01)).
-
Informed consent: Not applicable.
-
Author contributions: SM- Experimentation, analysis, Writing manuscript. LL- Experimentation, analysis, Writing manuscript. VPS- Experimentation, analysis, Writing manuscript. JP- Concept Design, Funding, Supervision, Experimentation, analysis, Writing manuscript. SEM- Experimentation, analysis, Writing manuscript. AN- Concept Design, Funding, Supervision, Experimentation, analysis, Writing manuscript.
-
Use of Large Language Models, AI and Machine Learning Tools: There is no AI tools used for writing. Support of Grammarly was used for language improvement.
-
Conflict of interest: The authors express that they have no conflict of interest in this study.
-
Research funding: None declared.
-
Data availability: The raw data can be obtained on request from the corresponding author.
References
1. Wei, S, Ma, W, Zhang, B, Li, W. NLRP3 inflammasome: a promising therapeutic target for drug-induced toxicity. Front Cell Dev Biol 2021;9:634607. https://doi.org/10.3389/fcell.2021.634607.Search in Google Scholar PubMed PubMed Central
2. Guengerich, FP. Mechanisms of drug toxicity and relevance to pharmaceutical development. Drug Metabol Pharmacokinet 2011;26:3–14. https://doi.org/10.2133/dmpk.dmpk-10-rv-062.Search in Google Scholar PubMed PubMed Central
3. Ayoub, SS. Paracetamol (acetaminophen): a familiar drug with an unexplained mechanism of action. Temperature (Austin, Tex.) 2021;8:351–71. https://doi.org/10.1080/23328940.2021.1886392.Search in Google Scholar PubMed PubMed Central
4. Jóźwiak-Bebenista, M, Nowak, JZ. Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm 2014;71:11–23.Search in Google Scholar
5. Rotundo, L, Pyrsopoulos, N. Liver injury induced by paracetamol and challenges associated with intentional and unintentional use. World J Hepatol 2020;12:125–36. https://doi.org/10.4254/wjh.v12.i4.125.Search in Google Scholar PubMed PubMed Central
6. Dahlin, DC, Miwa, GT, Lu, AY, Nelson, SD. N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. In: Proceedings of the national academy of sciences of the United States of America; 1984, vol 81:1327–31 p.10.1073/pnas.81.5.1327Search in Google Scholar PubMed PubMed Central
7. Gum, SI, Cho, MK. The amelioration of N-acetyl-p-benzoquinone imine toxicity by ginsenoside Rg3: the role of Nrf2-mediated detoxification and Mrp1/Mrp3 transports. Oxid Med Cell Longev 2013;2013:957947. https://doi.org/10.1155/2013/957947.Search in Google Scholar PubMed PubMed Central
8. van den Boogaard, WMC, Komninos, DSJ, Vermeij, WP. Chemotherapy side-effects: not all DNA damage is equal. Cancers (Basel) 2022;14. https://doi.org/10.3390/cancers14030627.Search in Google Scholar PubMed PubMed Central
9. Stone, RL, Cambron-Mellott, MJ, Beusterien, K, Maculaitis, MC, Ritz, S, Mulvihill, E, et al.. Patients’ and oncologists’ preferences for second-line maintenance PARP inhibitor therapy in epithelial ovarian cancer. Future oncol (London, England) 2022;18:491–503. https://doi.org/10.2217/fon-2021-0567.Search in Google Scholar PubMed
10. Culine, S, Harter, V, Gravis, G, Fléchon, A, Chevreau, C, Mahammedi, H, et al.. Chemotherapy for muscle-invasive bladder cancer: impact of cisplatin delivery on renal function and local control rate in the randomized phase III VESPER (GETUG-AFU V05) trial. Clin Genitourin Cancer 2021;19:554–62. https://doi.org/10.1016/j.clgc.2021.08.005.Search in Google Scholar PubMed
11. Zhang, Q, Lu, QB. New combination chemotherapy of cisplatin with an electron-donating compound for treatment of multiple cancers. Sci Rep 2021;11:020–80876. https://doi.org/10.1038/s41598-020-80876-z.Search in Google Scholar PubMed PubMed Central
12. Brown, A, Kumar, S, Tchounwou, PB. Cisplatin-based chemotherapy of human cancers. J Cancer Sci Ther 2019;11:8.Search in Google Scholar
13. Hussain, Y, Islam, L, Khan, H, Filosa, R, Aschner, M, Javed, S. Curcumin-cisplatin chemotherapy: a novel strategy in promoting chemotherapy efficacy and reducing side effects. Phytother Res 2021;35:6514–29. https://doi.org/10.1002/ptr.7225.Search in Google Scholar PubMed
14. Miller, RP, Tadagavadi, RK, Ramesh, G, Reeves, WB. Mechanisms of cisplatin nephrotoxicity. Toxins 2010;2:2490–518. https://doi.org/10.3390/toxins2112490.Search in Google Scholar PubMed PubMed Central
15. Volarevic, V, Djokovic, B, Jankovic, MG, Harrell, CR, Fellabaum, C, Djonov, V, et al.. Molecular mechanisms of cisplatin-induced nephrotoxicity: a balance on the knife edge between renoprotection and tumor toxicity. J Biomed Sci 2019;26:25. https://doi.org/10.1186/s12929-019-0518-9.Search in Google Scholar PubMed PubMed Central
16. Mapuskar, KA, Wen, H, Holanda, DG, Rastogi, P, Steinbach, E, Han, R, et al.. Persistent increase in mitochondrial superoxide mediates cisplatin-induced chronic kidney disease. Redox Biol 2019;20:98–106. https://doi.org/10.1016/j.redox.2018.09.020.Search in Google Scholar PubMed PubMed Central
17. Kaushal, GP, Chandrashekar, K, Juncos, LA. Molecular interactions between reactive oxygen species and autophagy in kidney disease. Int J Mol Sci 2019;20. https://doi.org/10.3390/ijms20153791.Search in Google Scholar PubMed PubMed Central
18. Yao, X, Panichpisal, K, Kurtzman, N, Nugent, K. Cisplatin nephrotoxicity: a review. Am J Med Sci 2007;334:115–24. https://doi.org/10.1097/maj.0b013e31812dfe1e.Search in Google Scholar
19. Dahl, JJ, Falk, K. Ayurvedic herbal supplements as an antidote to 9/11 toxicity. Alternative Ther Health Med 2008;14:24–8.Search in Google Scholar
20. Abdel-Aziz, AM, Mohamed, ASM, Abdelazem, O, Okasha, AMM, Kamel, MY. Cilostazol protects against cyclophosphamide-induced ovarian toxicity in female rats: role of cAMP and HO-1. Toxicol Mech Methods 2020;30:526–35. https://doi.org/10.1080/15376516.2020.1774829.Search in Google Scholar PubMed
21. Abdallah, HMI, Abdel-Rahman, RF, El Awdan, SA, Allam, RM, El-Mosallamy, AEMK, Selim, MS, et al.. Protective effect of some natural products against chemotherapy-induced toxicity in rats. Heliyon 2019;5:e01590. https://doi.org/10.1016/j.heliyon.2019.e01590.Search in Google Scholar PubMed PubMed Central
22. Saidurrahman, M, Mujahid, M, Siddiqui, MA, Alsuwayt, B, Rahman, MA. Evaluation of hepatoprotective activity of ethanolic extract of Pterocarpus marsupium Roxb. Leaves against paracetamol-induced liver damage via reduction of oxidative stress. Phytomed Plus 2022;2:100311. https://doi.org/10.1016/j.phyplu.2022.100311.Search in Google Scholar
23. Henneh, IT, Ahlidja, W, Alake, J, Kwabil, A, Ahmed, MA, Kyei-Asante, B, et al.. Ziziphus abyssinica root bark extract ameliorates paracetamol-induced liver toxicity in rats possibly via the attenuation of oxidative stress. Toxicol Rep 2022;9:1929–37. https://doi.org/10.1016/j.toxrep.2022.10.012.Search in Google Scholar PubMed PubMed Central
24. Hamza, AA, Hassanin, SO, Hamza, S, Abdalla, A, Amin, A. Polyphenolic-enriched olive leaf extract attenuated doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress and inflammation. J Basic and Appl Zoology 2021;82:54. https://doi.org/10.1186/s41936-021-00251-w.Search in Google Scholar
25. Qi, W, Boliang, W, Xiaoxi, T, Guoqiang, F, Jianbo, X, Gang, W. Cardamonin protects against doxorubicin-induced cardiotoxicity in mice by restraining oxidative stress and inflammation associated with Nrf2 signaling. Biomed Pharmacother 2020;122:109547. https://doi.org/10.1016/j.biopha.2019.109547.Search in Google Scholar PubMed
26. Lee, J, Nguyen, QN, Park, JY, Lee, S, Hwang, GS, Yamabe, N, et al.. Protective effect of shikimic acid against cisplatin-induced renal injury: in vitro and in vivo studies. Plants 2020;9:1681. https://doi.org/10.3390/plants9121681.Search in Google Scholar PubMed PubMed Central
27. Jurić, T, Katanić Stanković, JS, Rosić, G, Selaković, D, Joksimović, J, Mišić, D, et al.. Protective effects of Alchemilla vulgaris L. extracts against cisplatin-induced toxicological alterations in rats. South Afr J Bot 2020;128:141–51. https://doi.org/10.1016/j.sajb.2019.09.010.Search in Google Scholar
28. Mehrzadi, S, Fatemi, I, Esmaeilizadeh, M, Ghaznavi, H, Kalantar, H, Goudarzi, M. Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats. Biomed Pharmacother 2018;97:233–9. https://doi.org/10.1016/j.biopha.2017.10.113.Search in Google Scholar PubMed
29. Al Kury, LT, Dayyan, F, Ali Shah, F, Malik, Z, Khalil, AAK, Alattar, A, et al.. Ginkgo biloba extract protects against methotrexate-induced hepatotoxicity: a computational and pharmacological approach. Molecules 2020;25. https://doi.org/10.3390/molecules25112540.Search in Google Scholar PubMed PubMed Central
30. Castillo, L, Rossini, C. Bignoniaceae metabolites as semiochemicals. Molecules 2010;15:7090–105. https://doi.org/10.3390/molecules15107090.Search in Google Scholar PubMed PubMed Central
31. Dinda, B, SilSarma, I, Dinda, M, Rudrapaul, P. Oroxylum indicum (L.) Kurz, an important Asian traditional medicine: from traditional uses to scientific data for its commercial exploitation. J Ethnopharmacol 2015;161:255–78. https://doi.org/10.1016/j.jep.2014.12.027.Search in Google Scholar PubMed
32. Mishra, SL, Sinhamahapatra, PK, Nayak, A, Das, R, Sannigrahi, S. In vitro antioxidant potential of different parts of oroxylum indicum: a comparative study. Indian J Pharmaceut Sci 2010;72:267–9. https://doi.org/10.4103/0250-474x.65013.Search in Google Scholar PubMed PubMed Central
33. Zaveri, M, Khandhar, A, Jain, S. Quantification of baicalein, chrysin, biochanin-A and ellagic acid in root bark of oroxylum indicum by RP- HPLC with UV detection. Eurasian J Anal Chem 2008;3:245–57.Search in Google Scholar
34. Dunkhunthod, B, Talabnin, C, Murphy, M, Thumanu, K, Sittisart, P, Hengpratom, T, et al.. Intracellular ROS scavenging and anti-inflammatory activities of Oroxylum indicum Kurz (L.) extract in LPS plus IFN-γ-Activated RAW264.7 macrophages. Evid base Compl Alternative Med: eCAM 2020;2020:7436920. https://doi.org/10.1155/2020/7436920.Search in Google Scholar PubMed PubMed Central
35. Sithisarn, P, Nantateerapong, P, Rojsanga, P, Sithisarn, P. Screening for antibacterial and antioxidant activities and phytochemical analysis of Oroxylum indicum fruit extracts. Molecules 2016;21:446. https://doi.org/10.3390/molecules21040446.Search in Google Scholar PubMed PubMed Central
36. Hengpratom, T, Lowe, GM, Thumanu, K, Suknasang, S, Tiamyom, K, Eumkeb, G. Oroxylum indicum (L.) Kurz extract inhibits adipogenesis and lipase activity in vitro. BMC Complement Altern Med 2018;18:177. https://doi.org/10.1186/s12906-018-2244-3.Search in Google Scholar PubMed PubMed Central
37. Pondugula, SR, Majrashi, M, Almaghrabi, M, Ramesh, S, Abbott, KL, Govindarajulu, M, et al.. Oroxylum indicum ameliorates chemotherapy induced cognitive impairment. PLoS One 2021;16:e0252522. https://doi.org/10.1371/journal.pone.0252522.Search in Google Scholar PubMed PubMed Central
38. Pondugula, SR, Harshan, A, Ramesh, S, Govindarajulu, M, Almaghrabi, M, Majrashi, M, et al.. Cardioprotective effects of Oroxylum indicum extract against doxorubicin and cyclophosphamide-induced cardiotoxicity. Cardiovasc Toxicol 2022;22:67–77. https://doi.org/10.1007/s12012-021-09701-x.Search in Google Scholar PubMed
39. Menon, S, Albaqami, JJ, Hamdi, H, Lawrence, L, Divya, MK, Antony, L, et al.. Root bark extract of Oroxylum indicum vent. Inhibits solid and ascites tumors and prevents the development of DMBA-induced skin papilloma formation. Molecules 2022;27. https://doi.org/10.3390/molecules27238459.Search in Google Scholar PubMed PubMed Central
40. Menon, S, Albaqami, JJ, Hamdi, H, Lawrence, L, Divya, MK, Antony, L, et al.. Root bark extract of Oroxylum indicum vent. Inhibits solid and ascites tumors and prevents the development of DMBA-induced skin papilloma formation. Molecules 2022;27:8459. https://doi.org/10.3390/molecules27238459.Search in Google Scholar
41. Menon, S, Albaqami, JJ, Hamdi, H, Lawrence, L, Divya, MK, Antony, L, et al.. Root bark extract of Oroxylum indicum vent. Inhibits solid and ascites tumors and prevents the development of DMBA-induced skin papilloma formation. Molecules 2022;27. https://doi.org/10.3390/molecules27238459.Search in Google Scholar
42. Firdous, AP, Kuttan, R. Amelioration of cisplatin-induced toxicity in mice by carotenoid meso-zeaxanthin. Hum Exp Toxicol 2012;31:710–17. https://doi.org/10.1177/0960327111431707.Search in Google Scholar PubMed
43. McGinley, M, Wong, LL, McBride, JH, Rodgerson, DO. Comparison of various methods for the enumeration of blood cells in urine. J Clin Lab Anal 1992;6:359–61. https://doi.org/10.1002/jcla.1860060604.Search in Google Scholar PubMed
44. Ohkawa, H, Ohishi, N, Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8. https://doi.org/10.1016/0003-2697(79)90738-3.Search in Google Scholar PubMed
45. McCord, JM, Fridovich, I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 1969;244:6049–55. https://doi.org/10.1016/s0021-9258(18)63504-5.Search in Google Scholar
46. Hafeman, DG, Sunde, RA, Hoekstra, WG. Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J Nutr 1974;104:580–7. https://doi.org/10.1093/jn/104.5.580.Search in Google Scholar PubMed
47. Moron, MS, Depierre, JW, Mannervik, B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 1979;582:67–78. https://doi.org/10.1016/0304-4165(79)90289-7.Search in Google Scholar PubMed
48. Narayanankutty, A, Illam, SP, Rao, V, Shehabudheen, S, Raghavamenon, AC. Hot-processed virgin coconut oil abrogates cisplatin-induced nephrotoxicity by restoring redox balance in rats compared to fermentation-processed virgin coconut oil. Drug Chem Toxicol 2022;45:1373–82. https://doi.org/10.1080/01480545.2020.1831525.Search in Google Scholar PubMed
49. Palipoch, S, Punsawad, C. Biochemical and histological study of rat liver and kidney injury induced by cisplatin. J Toxicol Pathol 2013;26:293–9. https://doi.org/10.1293/tox.26.293.Search in Google Scholar PubMed PubMed Central
50. Aldhahrani, A, Ghamry, HI, Soliman, A, Alkafafy, M, Abduljabbar, MH, Farag, A, et al.. Potential beneficial effects of L-carnitine and allicin on doxorubicin induced nephrotoxicity in rats. Pak Vet J 2025;45:295–303.Search in Google Scholar
51. Elsayed, A, Aboubakr, M, Hassan, FW, Zakaria, M, Abdelhiee, EY, Soliman, A, et al.. Testicular injury of acrylamide in rats and potential protection of coenzyme Q10 and rosuvastatin. Pak Vet J 2024;44:344–51.Search in Google Scholar
52. Soliman, A, Alkafafy, M, Hassan, FW, Zakaria, M, Abduljabbar, MH, Mohamed, K, et al.. Investigating the protective role of L-carnitine and thymoquinone against methotrexate-induced testicular damage in rats. Pak Vet J 2024;44:314–21.Search in Google Scholar
53. Ray, S, Salzer, I, Kronschläger, MT, Boehm, S. The paracetamol metabolite N-acetylp-benzoquinone imine reduces excitability in first- and second-order neurons of the pain pathway through actions on KV7 channels. Pain 2019;160:954–64. https://doi.org/10.1097/j.pain.0000000000001474.Search in Google Scholar PubMed PubMed Central
54. Premkumar, K, Abraham, SK, Santhiya, ST, Ramesh, A. Protective effects of saffron (crocus sativus linn.) on genotoxins-induced oxidative stress in Swiss albino mice. Phytother Res 2003;17:614–17. https://doi.org/10.1002/ptr.1209.Search in Google Scholar PubMed
55. Song, J, Liu, D, Feng, L, Zhang, Z, Jia, X, Xiao, W. Protective effect of standardized extract of Ginkgo biloba against cisplatin-induced nephrotoxicity. Evid base Compl Alternative Med: eCAM 2013;2013:846126. https://doi.org/10.1155/2013/846126.Search in Google Scholar PubMed PubMed Central
56. Sugihara, K, Nakano, S, Koda, M, Tanaka, K, Fukuishi, N, Gemba, M. Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues. Jpn J Pharmacol 1987;43:247–52. https://doi.org/10.1016/s0021-5198(19)43504-x.Search in Google Scholar
57. Ingale, KG, Thakurdesai, PA, Vyawahare, NS. Protective effect of Hygrophila spinosa against cisplatin induced nephrotoxicity in rats. Indian J Pharmacol 2013;45:232–6. https://doi.org/10.4103/0253-7613.111909.Search in Google Scholar PubMed PubMed Central
58. Çetin, R, Devrim, E, Kılıçoğlu, B, Avcı, A, Çandır, Ö, Durak, İ. Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods. J Appl Toxicol 2006;26:42–6. https://doi.org/10.1002/jat.1103.Search in Google Scholar PubMed
59. Atessahin, A, Yilmaz, S, Karahan, I, Ceribasi, AO, Karaoglu, A. Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats. Toxicology 2005;212:116–23. https://doi.org/10.1016/j.tox.2005.04.016.Search in Google Scholar PubMed
60. Ramesh, G, Reeves, WB. TNFR2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure. Am J Physiol Ren Physiol 2003;285:F610–18. https://doi.org/10.1152/ajprenal.00101.2003.Search in Google Scholar PubMed
61. Wood, PA, Hrushesky, WJ. Cisplatin-associated anemia: an erythropoietin deficiency syndrome. J Clin Investig 1995;95:1650–9. https://doi.org/10.1172/jci117840.Search in Google Scholar
62. Ahmad, A, Husain, A, Mujeeb, M, Khan, SA, Najmi, AK, Siddique, NA, et al.. A review on therapeutic potential of nigella sativa: a miracle herb. Asian Pac J Trop Biomed 2013;3:337–52. https://doi.org/10.1016/s2221-1691(13)60075-1.Search in Google Scholar PubMed PubMed Central
63. Geetha, BS, Latha, PG, Remani, P. Amelioration of cisplatin induced toxicity in normal mice by plant based antitumor drug, Elephantopus scaber L. Asian J Ethnopharmacol Med Food 2015;1:20–4.Search in Google Scholar
64. Sultana, S, Verma, K, Khan, R. Nephroprotective efficacy of chrysin against cisplatin-induced toxicity via attenuation of oxidative stress. J Pharm Pharmacol 2012;64:872–81. https://doi.org/10.1111/j.2042-7158.2012.01470.x.Search in Google Scholar PubMed
65. Atessahin, A, Ceribasi, AO, Yuce, A, Bulmus, O, Cikim, G. Role of ellagic acid against cisplatin-induced nephrotoxicity and oxidative stress in rats. Basic Clin Pharmacol Toxicol 2007;100:121–6. https://doi.org/10.1111/j.1742-7843.2006.00015.x.Search in Google Scholar PubMed
66. Sahu, BD, Kumar, JM, Sistla, R, Baicalein, a bioflavonoid prevents cisplatin-induced acute kidney injury by up-regulating antioxidant defenses and down-regulating the MAPKs and NF-κB pathways. PLoS One 2015;10:e0134139. https://doi.org/10.1371/journal.pone.0134139.Search in Google Scholar PubMed PubMed Central
67. Wang, X, Ding, G, Liu, B, Wang, Q. Flavonoids and antioxidant activity of rare and endangered fern: isoetes sinensis. PLoS One 2020;15:e0232185. https://doi.org/10.1371/journal.pone.0232185.Search in Google Scholar PubMed PubMed Central
68. Tungmunnithum, D, Thongboonyou, A, Pholboon, A, Yangsabai, A. Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: an overview. Medicines 2018;5. https://doi.org/10.3390/medicines5030093.Search in Google Scholar PubMed PubMed Central
69. Bahekar, SE, Kale, RS. Evaluation of antioxidant activity of Manihot esculenta crantz in wistar rats. J Pharm BioAllied Sci 2016;8:119–23. https://doi.org/10.4103/0975-7406.171697.Search in Google Scholar PubMed PubMed Central
70. Sant, KE, Hansen, JM, Williams, LM, Tran, NL, Goldstone, JV, Stegeman, JJ, et al.. The role of Nrf1 and Nrf2 in the regulation of glutathione and redox dynamics in the developing zebrafish embryo. Redox Biol 2017;13:207–18. https://doi.org/10.1016/j.redox.2017.05.023.Search in Google Scholar PubMed PubMed Central
71. Wei, Y, Lu, M, Mei, M, Wang, H, Han, Z, Chen, M, et al.. Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection. Nat Commun 2020;11:941. https://doi.org/10.1038/s41467-020-14788-x.Search in Google Scholar PubMed PubMed Central
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/znc-2025-0088).
© 2025 Walter de Gruyter GmbH, Berlin/Boston