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Volume 13, Issue 4 (Vol.13 No.4 Jan 2025)
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Shariati S, Khodayar M J, Azadnasab R, Moghtadaei N, Khorsandi L, Shirani M. Protective Effects of Vanillic Acid on Arsenic-Induced Hepatotoxicity and Diabetes in Mice; the Role of PPARγ and NF-κB Signaling. rbmb.net 2025; 13 (4) :549-560
URL: http://rbmb.net/article-1-1501-en.html
URL: http://rbmb.net/article-1-1501-en.html
Saeedeh Shariati 
, Mohammad Javad Khodayar , Reza Azadnasab , Narjes Moghtadaei , Layasadat Khorsandi , Maryam Shirani *
, Mohammad Javad Khodayar , Reza Azadnasab , Narjes Moghtadaei , Layasadat Khorsandi , Maryam Shirani *
Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Abstract: (198 Views)
Background: Arsenic (As), a toxic metalloid present in drinking water, is one of the environmental pollutants associated with diabetes in humans. Vanillic acid (VA), a bioactive compound derived from plants has various medicinal activities.
Methods: This study was conducted on NMRI male mice for 8 weeks. forty mice were randomly divided into control group, As group (50 ppm), VA (100 mg/kg) group, and two groups receiving As (50 ppm) and VA with doses of 50 mg/kg and 100 mg/kg. After 56 days of the study, the mice were fasted overnight and on day 57, fasting blood glucose was measured, and glucose tolerance test was performed. On day 59, mice were euthanized and serum factors, markers of oxidative stress, tumor necrosis factor-α (TNF-α), and expression nuclear factor kappa B (NF-κB) and Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) proteins were measured.
Results: The As significantly increased fasting blood sugar, the activity level of liver function enzymes, thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), TNF-α, and NF-κB expression. Furthermore, As decreased hepatic total thiol (TT) and activity levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and expression of PPARγ. VA decreased the altered liver enzymes, hyperglycemia, NO, TBARS, TNF-α and the expression of NF-κB. Furthermore, increased the hepatic activity of the CAT, SOD, and GPx, TT and the expression of PPARγ.
Conclusion: The administration of VA at doses of 50 and 100 mg/kg demonstrated significant mitigation of the toxic effects induced by As on the liver.
Methods: This study was conducted on NMRI male mice for 8 weeks. forty mice were randomly divided into control group, As group (50 ppm), VA (100 mg/kg) group, and two groups receiving As (50 ppm) and VA with doses of 50 mg/kg and 100 mg/kg. After 56 days of the study, the mice were fasted overnight and on day 57, fasting blood glucose was measured, and glucose tolerance test was performed. On day 59, mice were euthanized and serum factors, markers of oxidative stress, tumor necrosis factor-α (TNF-α), and expression nuclear factor kappa B (NF-κB) and Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) proteins were measured.
Results: The As significantly increased fasting blood sugar, the activity level of liver function enzymes, thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), TNF-α, and NF-κB expression. Furthermore, As decreased hepatic total thiol (TT) and activity levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and expression of PPARγ. VA decreased the altered liver enzymes, hyperglycemia, NO, TBARS, TNF-α and the expression of NF-κB. Furthermore, increased the hepatic activity of the CAT, SOD, and GPx, TT and the expression of PPARγ.
Conclusion: The administration of VA at doses of 50 and 100 mg/kg demonstrated significant mitigation of the toxic effects induced by As on the liver.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2024/10/27 | Accepted: 2024/12/26 | Published: 2025/07/30
Received: 2024/10/27 | Accepted: 2024/12/26 | Published: 2025/07/30
References
1. Badiee MS, Vadizadeh A, Salehcheh M, Moosavi M, Shirani M, Fakhredini F, Khodayar MJ. Quercetin and catechin protects leptin-deficient Lepob/Ob mice against alloxan-induced diabetes and hepatotoxicity via suppression of oxidative stress and inflammation. Rep Biochem Mol Biol. 2024: 13(2):184-195. [DOI:10.61186/rbmb.13.2.184] [PMID] []
2. Ramadan SS, Almeer R, Albasher G, Abdel Moneim AE. Lycopene mitigates arsenic-induced nephrotoxicity with activation of the Nrf2 pathway in mice. Toxin Rev. 2021;41(2):446-56. [DOI:10.1080/15569543.2021.1891938]
3. Shariati S, Shirani M, Azadnasab R, Khorsandi L, Khodayar MJ. Betaine Protects Mice from Cardiotoxicity Triggered by Sodium Arsenite Through Antioxidative and Anti-inflammatory Pathways. Cardiovasc Toxicol. 2024;24(6):539-549. [DOI:10.1007/s12012-024-09864-3] [PMID]
4. Khodayar MJ, Shirani M, Shariati S, Khorsandi L, Mohtadi S. Antioxidant and anti-inflammatory potential of vanillic acid improves nephrotoxicity induced by sodium arsenite in mice. Int J Environ Health Res. 2024:1-11. [DOI:10.1080/09603123.2024.2439452] [PMID]
5. Mohtadi S, Shariati S, Mansouri E, Khodayar MJ. Nephroprotective effect of diosmin against sodium arsenite-induced renal toxicity is mediated via attenuation of oxidative stress and inflammation in mice. Pestic Biochem Physiol. 2023;197:105652. [DOI:10.1016/j.pestbp.2023.105652] [PMID]
6. Khodayar MJ, Shirani M, Nikravesh M, Mohammadi E, Khorsandi LS, Shariati S. Protective effect of citicoline on sodium arsenite-induced nephrotoxicity in mice. Jundishapur J Nat Pharm Prod. 2024: 19(2):e144745. [DOI:10.5812/jjnpp-144745]
7. Yang Y, Song S, Nie Y, Chen R, Chen P. Lentinan alleviates arsenic-induced hepatotoxicity in mice via downregulation of OX40/IL-17A and activation of Nrf2 signaling. BMC Pharmacol Toxicol. 2022;23(1):16.
https://doi.org/10.1186/s40360-016-0059-8 [DOI:10.1186/s40360-022-00557-7]
8. Hejazi S, Moosavi M, Molavinia S, Mansouri E, Azadnasab R, Khodayar MJ. Epicatechin ameliorates glucose intolerance and hepatotoxicity in sodium arsenite-treated mice. Food Chem Toxicol. 2024;192:114950. [DOI:10.1016/j.fct.2024.114950] [PMID]
9. Molavinia S, Moosavi M, Hejazi S, Azadnasab R, Mansouri E, Khodayar MJ. Metformin alleviates sodium arsenite-induced hepatotoxicity and glucose intolerance in mice by suppressing oxidative stress, inflammation, and apoptosis. J Trace Elem Med Biol. 2023;80:127299. [DOI:10.1016/j.jtemb.2023.127299] [PMID]
10. Liu S, Guo X, Wu B, Yu H, Zhang X, Li M. Arsenic induces diabetic effects through beta-cell dysfunction and increased gluconeogenesis in mice. Sci Rep. 2014;4:6894. [DOI:10.1038/srep06894] [PMID] []
11. Ijaz MU, Ahmed A, Al-Ghanim KA, Al-Misned F, Riaz MN, Kaimkhani ZA, Mahboob S. Evaluation of the Possible Protective Role of Nobiletin against Arsenic-Induced Liver Damage in Male Albino Rats. Toxics. 2023;11(2):110. [DOI:10.3390/toxics11020110] [PMID] []
12. Singh B, Kumar A, Singh H, Kaur S, Arora S, Singh B. Protective effect of vanillic acid against diabetes and diabetic nephropathy by attenuating oxidative stress and upregulation of NF-κB, TNF-α and COX-2 proteins in rats. Phytother Res. 2022;36(3):1338-1352. [DOI:10.1002/ptr.7392] [PMID]
13. Dhananjaya BL, Nataraju A, Raghavendra Gowda CD, Sharath BK, D'Souza CJ. Vanillic acid as a novel specific inhibitor of snake venom 5'-nucleotidase: a pharmacological tool in evaluating the role of the enzyme in snake envenomation. Biochemistry (Mosc). 2009;74(12):1315-9. [DOI:10.1134/S0006297909120037] [PMID]
14. Dhananjaya BL, Nataraju A, Rajesh R, Raghavendra Gowda CD, Sharath BK, Vishwanath BS, D'Souza CJ. Anticoagulant effect of Naja naja venom 5'nucleotidase: demonstration through the use of novel specific inhibitor, vanillic acid. Toxicon. 2006;48(4):411-21. [DOI:10.1016/j.toxicon.2006.06.017] [PMID]
15. Baniahmad B, Safaeian L, Vaseghi G, Rabbani M, Mohammadi B. Cardioprotective effect of vanillic acid against doxorubicin-induced cardiotoxicity in rat. Res Pharm Sci. 2020;15(1):87-96. [DOI:10.4103/1735-5362.278718] [PMID] []
16. Amin FU, Shah SA, Kim MO. Vanillic acid attenuates Aβ1-42-induced oxidative stress and cognitive impairment in mice. Sci Rep. 2017;7:40753. [DOI:10.1038/srep40753] [PMID] []
17. Itoh A, Isoda K, Kondoh M, Kawase M, Kobayashi M, Tamesada M, Yagi K. Hepatoprotective effect of syringic acid and vanillic acid on concanavalin a-induced liver injury. Biol Pharm Bull. 2009;32(7):1215-9. [DOI:10.1248/bpb.32.1215] [PMID]
18. Kim SJ, Kim MC, Um JY, Hong SH. The beneficial effect of vanillic acid on ulcerative colitis. Molecules. 2010;15(10):7208-17. [DOI:10.3390/molecules15107208] [PMID] []
19. Sharma D, Bhattacharya P, Kalia K, Tiwari V. Diabetic nephropathy: New insights into established therapeutic paradigms and novel molecular targets. Diabetes Res Clin Pract. 2017;128:91-108. [DOI:10.1016/j.diabres.2017.04.010] [PMID]
20. Cho HH, Jang SH, Won C, Kim CH, Kim HD, Kim TH, Cho JH. Derhamnosylmaysin Inhibits Adipogenesis via Inhibiting Expression of PPARγ and C/EBPα in 3T3-L1 Cells. Molecules. 2022;27(13):4232. [DOI:10.3390/molecules27134232] [PMID] []
21. Rangwala SM, Lazar MA. Peroxisome proliferator-activated receptor gamma in diabetes and metabolism. Trends Pharmacol Sci. 2004;25(6):331-6. [DOI:10.1016/j.tips.2004.03.012] [PMID]
22. Jung Y, Park J, Kim HL, Sim JE, Youn DH, Kang J, et al. Vanillic acid attenuates obesity via activation of the AMPK pathway and thermogenic factors in vivo and in vitro. FASEB J. 2018;32(3):1388-1402. [DOI:10.1096/fj.201700231RR] [PMID]
23. Kumari S, Kamboj A, Wanjari M, Sharma AK. Nephroprotective effect of Vanillic acid in STZ-induced diabetic rats. J Diabetes Metab Disord. 2021;20(1):571-582. [DOI:10.1007/s40200-021-00782-7] [PMID] []
24. Kalantari H, Khodayar MJ, Saki N, Khorsandi L, Teymoori A, Alidadi H, Samimi A. Microarray analysis of apoptosis gene expression in liver injury induced by chronic exposure to arsenic and high-fat diet in male mice. Environ Sci Pollut Res Int. 2019;26(25):26351-26366. [DOI:10.1007/s11356-019-05907-3] [PMID]
25. Molavinia S, Moosavi M, Hejazi S, Azadnasab R, Mansouri E, Khodayar MJ. Metformin alleviates sodium arsenite-induced hepatotoxicity and glucose intolerance in mice by suppressing oxidative stress, inflammation, and apoptosis. J Trace Elem Med Biol. 2023;80:127299. [DOI:10.1016/j.jtemb.2023.127299] [PMID]
26. Kumar M, Thakur R. Syzygium cumini seed extract ameliorates arsenic-induced blood cell genotoxicity and hepatotoxicity in Wistar albino rats. Reports Biochem Mol Biol. 2018;7(1):110-8.
27. Rahaman MS, Rahman MM, Mise N, Sikder MT, Ichihara G, Uddin MK, et al. Environmental arsenic exposure and its contribution to human diseases, toxicity mechanism, and management. Environ Pollut. 2021;289:117940. [DOI:10.1016/j.envpol.2021.117940] [PMID]
28. Grau-Pérez M, Kuo CC, Spratlen M, Thayer KA, Mendez MA, Hamman RF, et al. The Association of Arsenic Exposure and Metabolism With Type 1 and Type 2 Diabetes in Youth: The SEARCH Case-Control Study. Diabetes Care. 2017;40(1):46-53. [DOI:10.2337/dc16-0810] [PMID] []
29. Liu J, Hermon T, Gao X, Dixon D, Xiao H. Arsenic and Diabetes Mellitus: A Putative Role for the Immune System. All Life. 2023;16(1):2167869. [DOI:10.1080/26895293.2023.2167869] [PMID] []
30. Ghasemi-Dehnoo M, Amini-Khoei H, Lorigooini Z, Rafieian-Kopaei M. Oxidative stress and antioxidants in diabetes mellitus. Asian Pac J Trop Med. 2020;13(10):431-8. [DOI:10.4103/1995-7645.291036]
31. Chen SC, Tsai SP, Jhao JY, Jiang WK, Tsao CK, Chang LY. Liver Fat, Hepatic Enzymes, Alkaline Phosphatase and the Risk of Incident Type 2 Diabetes: A Prospective Study of 132,377 Adults. Sci Rep. 2017;7(1):4649. [DOI:10.1038/s41598-017-04631-7] [PMID] []
32. Esfahani PP, Mahdavinia M, Khorsandi L, Rezaei M, Nikravesh H, Khodayar MJ. Betaine protects against sodium arsenite-induced diabetes and hepatotoxicity in mice. Environ Sci Pollut Res Int. 2023;30(4):10880-10889. [DOI:10.1007/s11356-022-22941-w] [PMID]
33. Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D, Rhodes CJ, Valko M. Arsenic: toxicity, oxidative stress and human disease. J Appl Toxicol. 2011;31(2):95-107. [DOI:10.1002/jat.1649] [PMID]
34. Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol. 2005;4:5. [DOI:10.1186/1475-2840-4-5] [PMID] []
35. Vinothiya K, Ashokkumar N. Modulatory effect of vanillic acid on antioxidant status in high fat diet-induced changes in diabetic hypertensive rats. Biomed Pharmacother. 2017;87:640-52. [DOI:10.1016/j.biopha.2016.12.134] [PMID]
36. Zelová H, Hošek J. TNF-α signalling and inflammation: interactions between old acquaintances. Inflamm Res. 2013;62(7):641-51. [DOI:10.1007/s00011-013-0633-0] [PMID]
37. Nasrollahzadeh A, Momeny M, Bashash D, Yousefi H, Mousavi SA, Ghaffari SH. Blockade of Nuclear Factor-Κb (NF-Κb) Pathway Using Bay 11-7082 Enhances Arsenic Trioxide-Induced Antiproliferative Activity in U87 Glioblastoma Cells. Rep Biochem Mol Biol. 2022;10(4):602-613. [DOI:10.52547/rbmb.10.4.602] [PMID] []
38. Van Antwerp DJ, Martin SJ, Verma IM, Green DR. Inhibition of TNF-induced apoptosis by NF-kappa B. Trends Cell Biol. 1998;8(3):107-11. [DOI:10.1016/S0962-8924(97)01215-4] [PMID]
39. Hohmann HP, Brockhaus M, Baeuerle PA, Remy R, Kolbeck R, van Loon AP. Expression of the types A and B tumor necrosis factor (TNF) receptors is independently regulated, and both receptors mediate activation of the transcription factor NF-kappa B. TNF alpha is not needed for induction of a biological effect via TNF receptors. J Biol Chem. 1990;265(36):22409-17. [DOI:10.1016/S0021-9258(18)45720-1] [PMID]
40. Aktan F. iNOS-mediated nitric oxide production and its regulation. Life Sci. 2004;75(6):639-53. [DOI:10.1016/j.lfs.2003.10.042] [PMID]
41. Zand H, Morshedzadeh N, Naghashian F. Signaling pathways linking inflammation to insulin resistance. Diabetes Metab Syndr. 2017;11 Suppl 1:S307-S309. [DOI:10.1016/j.dsx.2017.03.006] [PMID]
42. Fouad AA, Al-Mulhim AS, Jresat I. Telmisartan treatment attenuates arsenic-induced hepatotoxicity in mice. Toxicology. 2012;300(3):149-57. [DOI:10.1016/j.tox.2012.06.015] [PMID]
43. Daryagasht M, Moosavi M, Khorsandi L, Azadnasab R, Khodayar MJ. Hepatoprotective and anti-hyperglycemic effects of ferulic acid in arsenic-exposed mice. Food Chem Toxicol. 2023;178:113924. [DOI:10.1016/j.fct.2023.113924] [PMID]
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