Investigating the effect of telmisartan on acrylamide-induced neurotoxicity through in vitro and in vivo methods

Document Type : Original Article

Authors

1 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

3 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s):  Acrylamide (ACR) is an environmental contaminant and neurotoxin. Telmisartan is an AT1 blocker that has neuroprotective properties basically through its anti-oxidant effect. The effect of telmisartan on ACR-induced neurotoxicity was investigated in this study. 
Materials and Methods: Male Wistar rats were randomly assigned to eight groups (n=6): 1:Control (normal saline), 2:ACR (50 mg/kg, 11 days, IP), 3:ACR+vitamin E (200 mg/kg, every other day, 11 days), 4-6:ACR+telmisartan (0.6, 1.25, and 2.5 mg/kg, 11 days, IP), 7:ACR+telmisartan (0.6 mg/kg, days 3–11), 8:Telmisartan (2.5 mg/kg, 11 days). The behavioral test and blood pressure were assessed after 11 days. Then, the levels of MDA and GSH in brain tissue were measured. The MTT assay was used to evaluate the effect of telmisartan on ACR-induced cytotoxicity.
Results: Exposing PC12 cells to ACR decreased cell viability versus the control group. Pretreating PC12 cells with telmisartan (0.0125, 0.025 µM) enhanced cell viability compared with the ACR group. Compared with control samples, ACR significantly caused motor impairment, elevated MDA, and reduced GSH levels. Locomotor abnormalities were significantly ameliorated by telmisartan (0.6, 1.25 mg/kg, 11 days) and vitamin E versus the ACR group. Receiving telmisartan (0.6, 1.25, and 2.5 mg/kg) and vitamin E along with ACR decreased MDA levels and enhanced GSH content compared with the ACR group.  There was no significant difference in animal blood pressure between the groups.
Conclusion: Oxidative stress has a chief role in the neurotoxicity of ACR. Telmisartan (in doses that do not affect blood pressure) ameliorated ACR-induced toxicity by inhibiting oxidative stress.

Keywords

Main Subjects

References

1. Park JS, Samanta P, Lee S, Lee J, Cho JW, Chun HS, et al. Developmental and neurotoxicity of acrylamide to zebrafish. Int J Mol Sci 2021; 22:3518.
2. Ghasemzadeh Rahbardar M, Hemadeh B, Razavi BM, Eisvand F, Hosseinzadeh H. Effect of carnosic acid on acrylamide induced neurotoxicity: in vivo and in vitro experiments. Drug Chem Toxicol 2022; 45:1528-1535.
3. Zhao M, Zhang B, Deng L. The mechanism of acrylamide-induced neurotoxicity: Current status and future perspectives. Front Nutr 2022; 9:859189.
4. Powers SJ, Mottram DS, Curtis A, Halford NG. Acrylamide levels in potato crisps in Europe from 2002 to 2016. Food Addit Contam 2017; 34:2085-2100.
5. Bušová M, Bencko V, Laktičová KV, Holcátová I, Vargová M. Risk of exposure to acrylamide. Cent Eur J Public Health 2020; 28:S43-S46.
6. Yedier SK, Şekeroğlu ZA, Şekeroğlu V, Aydın B. Cytotoxic, genotoxic, and carcinogenic effects of acrylamide on human lung cells. Food Chem Toxicol 2022; 161:112852.
7. Yue Z, Tian E, Chen Y, Luo L, Yang L, He L, et al. The adverse effects of acrylamide exposure on the early development of marine medaka (Oryzias melastigma) and its mechanisms. Mar Pollut Bull 2021; 163:111875.
8. Rahbardar MG, Farmad HC, Hosseinzadeh H, Mehri S. Protective effects of selenium on acrylamide-induced neurotoxicity and hepatotoxicity in rats. Iran J Basic Med Sci 2021; 24:1041–1049.
9. Faria M, Ziv T, Gómez-Canela C, Ben-Lulu S, Prats E, Novoa-Luna KA, et al. Acrylamide acute neurotoxicity in adult zebrafish. Sci Rep 2018; 8:1-14.
10. Wang S, Zhang Y, Lou J, Yong H, Shan S, Liu Z, et al. The therapeutic potential of berberine chloride against SARM1‐dependent axon degeneration in acrylamide‐induced neuropathy. Phytother Res 2022.
11. Pan X, Zhu L, Lu H, Wang D, Lu Q, Yan H. Melatonin attenuates oxidative damage induced by acrylamide in vitro and in vivo. Oxid Med Cell Longev 2015; 2015:703709.
12. Esmaeelpanah E, Razavi BM, Vahdati Hasani F, Hosseinzadeh H. Evaluation of epigallocatechin gallate and epicatechin gallate effects on acrylamide-induced neurotoxicity in rats and cytotoxicity in PC 12 cells. Drug Chem Toxicol 2018; 41:441-448.
13.Mehri S, Abnous K, Khooei A, Mousavi SH, Shariaty VM, Hosseinzadeh H. Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition of oxidative stress. Iran J Basic Med Sci 2015; 18:902–908.
14. Abd El Aziz AE, Sayed RH, Sallam NA, El Sayed NS. Neuroprotective effects of telmisartan and nifedipine against cuprizone-induced demyelination and behavioral dysfunction in mice: roles of NF-κB and Nrf2. Inflammation 2021; 44:1629-1642.
15. Rasheed NOA, Ibrahim WW. Telmisartan neuroprotective effects in 3-nitropropionic acid Huntington’s disease model in rats: Cross talk between PPAR-γ and PI3K/Akt/GSK-3β pathway. Life Sci 2022; 297:120480.
16. Tandisehpanah Z, Foroutanfar A, Aziminia A, Rahbardar MG, Razavi BM, Hosseinzadeh H. Protective effect of aqueous and ethanolic extracts of Lippia citriodora Kunth. on acrylamide-induced neurotoxicity. Avicenna J Phytomed 2022; 12:281-294.
17. Mehri S, Shahi M, Razavi BM, Hassani FV, Hosseinzadeh H. Neuroprotective effect of thymoquinone in acrylamide-induced neurotoxicity in Wistar rats. Iran J Basic Med Sci 2014; 17:1007–1011.
18. Esmaeelpanah E, Rahmatkhah A, Poormahmood N, Razavi BM, Hasani FV, Hosseinzadeh H. Protective effect of green tea aqueous extract on acrylamide induced neurotoxicity. Jundishapur J Nat Pharm Prod 2015; 10:e18406.
19. Ardakanian A, Rahbardar MG, Omidkhoda F, Razavi BM, Hosseinzadeh H. Effect of alpha-mangostin on olanzapine-induced metabolic disorders in rats. Iran J Basic Med Sci 2022; 25:198-207.
20. Fadishei M, Ghasemzadeh Rahbardar M, Imenshahidi M, Mohajeri A, Razavi BM, Hosseinzadeh H. Effects of Nigella sativa oil and thymoquinone against bisphenol A‐induced metabolic disorder in rats. Phytother Res 2021; 35:2005-2024.
21. Rahbardar MG, Eisvand F, Rameshrad M, Razavi BM, Hosseinzadeh H. In vivo and in vitro protective effects of rosmarinic acid against doxorubicin-induced cardiotoxicity. Nutr Cancer 2022; 74:747-760.
22. Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978; 86:271-278.
23. Ghasemzadeh Rahbardar M, Razavi BM, Hosseinzadeh H. Investigating the ameliorative effect of alpha‐mangostin on development and existing pain in a rat model of neuropathic pain. Phytother Res 2020; 34:3211-3225.
24. 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.
25. Kwon HS, Ha J, Kim JY, Park H-H, Lee E-H, Choi H, et al. Telmisartan inhibits the NLRP3 inflammasome by activating the PI3K pathway in neural stem cells injured by oxygen-glucose deprivation. Mol Neurobiol 2021; 58:1806-1818.
26. Pang T, Sun L-x, Wang T, Jiang Z-z, Liao H, Zhang L-yJAPS. Telmisartan protects central neurons against nutrient deprivation-induced apoptosis in vitro through activation of PPARγ and the Akt/GSK-3β pathway. Acta Pharmacol Sin 2014; 35:727-737.
27. Kopańska M, Łagowska A, Kuduk B, Banaś-Ząbczyk A. Acrylamide neurotoxicity as a possible factor responsible for inflammation in the cholinergic nervous system. Int J Mol Sci 2022; 23:2030.
28. Kumar PP, KV HP. Low molecular weight chitosan (∼ 20 kDa) protects acrylamide induced oxidative stress in D. melanogaster by restoring dopamine and KIF5B levels. Carbohydr Polym 2019; 222:115005.
29. Foroutanfar A, Mehri S, Kamyar M, Tandisehpanah Z, Hosseinzadeh H. Protective effect of punicalagin, the main polyphenol compound of pomegranate, against acrylamide‐induced neurotoxicity and hepatotoxicity in rats. Phytother Res 2020; 34:3262-3272.
30. Khallaf WA, Messiha BA, Abo-Youssef AM, El-Sayed NSJCJoP, Pharmacology. Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: Possible role of brain-derived neurotrophic factor. Can J Physiol Pharmacol 2017; 95:850-860.
Iranian Journal of Basic Medical Sciences
Volume 26, Issue 9
September 2023
Pages 1024-1029

Files

Share

How to cite

Statistics