Can idebenone protect gastric tissue against oxidative stress, inflammation, and necrosis?
DOI:
https://doi.org/10.1590/s2175-97902025e24246Keywords:
Anti-inflammatory, Antioxidant, Gastric ulcer, Idebenone, IndomethacinAbstract
This study aims to investigate the antiulcer effects of Idebenone (IDE) in Wistar rats with indomethacininduced gastric ulcer and compare its effectiveness with famotidine (FAM). 36 rats were randomly divided into six groups: healthy; healthy+IDE200; ulcer (U); U+FAM; U+IDE100; U+IDE200. Six hours after the administration of 25 mg/kg of indomethacin, the antiulcer effects of FAM (40 mg/kg) and two different doses of IDE (100 and 200 mg/kg) in the gastric tissue of rats were examined through macroscopic, biochemical, molecular, and histopathological analyses. Comparative assessments were conducted between the healthy control group and the group treated with indomethacin alone. IDE effectively suppressed the indomethacin-induced increase in malondialdehyde (MDA) and mitigated the reduction in glutathione (GSH) levels. Furthermore, IDE treatment led to a significant decrease in mRNA expressions of interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa beta (NF-κB)-p65 in ulcerative rats. Histopathological examinations revealed that both IDE doses improved the ulcer damage caused by indomethacin in the rats' stomach tissues. This study demonstrates that IDE administration exhibits a protective effect against indomethacin-induced gastric ulcers by reducing oxidative stress and inflammatory processes. IDE’s potential to prevent ulcer formation in the gastric tissue of rats suggests that it could be a valuable therapeutic agent in clinical practice.
Downloads
References
Abdelzaher WY, Mostafa-Hedeab G, Sayed Abobakr Ali AH, Fawzy MA, Ahmed AF, Bahaa El-Deen MA, et al. Idebenone regulates sirt1/Nrf2/TNF-alpha pathway with inhibition of oxidative stress, inflammation, and apoptosis in testicular torsion/detorsion in juvenile rats. Hum Exp Toxicol. 2022;41:1-11.
Akanda MR, Park BY. Involvement of MAPK/NFkappaB signal transduction pathways: camellia japonica mitigates inflammation and gastric ulcer. Biomed Pharmacother. 2017;95:1139-1146.
Akpinar E, Kutlu Z, Kose D, Aydin P, Tavaci T, Bayraktutan Z, et al. Protective effects of idebenone against sepsis induced acute lung damage. J Invest Surg. 2022;35(3):560-568.
Al-Rasheed NM, Faddah LM, Mohamed AM, Abdel Baky NA, Al-Rasheed NM, Mohammad RA. Potential impact of quercetin and idebenone against immunoinflammatory and oxidative renal damage induced in rats by titanium dioxide nanoparticles toxicity. J Oleo Sci. 2013;62(11):961-971.
Alatawi YF, Alhablani MA, Al-Rashidi FA, Khubrani WS, Alqaisi SA, Hassan HM, et al. Garcinol-attenuated gastric ulcer (GU) experimentally induced in rats via affecting inflammation, cell proliferation, and DNA polymerization. Cureus. 2023 (in press).
Alkreathy HM, Alghamdi MK, Esmat A. Tetramethylpyrazine ameliorates indomethacininduced gastric ulcer in rats: impact on oxidative, inflammatory, and angiogenic machineries. Saudi Pharm J. 2020;28(8):916-926.
Avci B, Gunaydin C, Guvenc T, Yavuz CK, Kuruca N, Bilge SS. Idebenone ameliorates rotenone-induced parkinson's disease in rats through decreasing lipid peroxidation. Neurochem Res. 2021;46(3):513-522.
Azim SA, Darwish HA, Rizk MZ, Ali SA, Kadry MO. Amelioration of titanium dioxide nanoparticles-induced liver injury in mice: possible role of some antioxidants. Exp Toxicol Pathol. 2015;67(4):305-314.
Balaha MF, Almalki ZS, Alahmari AK, Ahmed NJ, Balaha MF. AMPK/mTOR-driven autophagy & Nrf2/HO-1 cascade modulation by amentoflavone ameliorates indomethacin-induced gastric ulcer. Biomed Pharmacother. 2022 (in press).
Barboza KRM, Coco LZ, Alves GM, Peters B, Vasquez EC, Pereira TMC, et al. Gastroprotective effect of oral kefir on indomethacin-induced acute gastric lesions in mice: impact on oxidative stress. Life Sci. 2018;209:370-376.
Bayir Y, Tagiyeva N, Albayrak A, Ismayilov A, Akpinar E, Toktay E, et al. Effects of polygonum cognatum meissn extract on indomethacin induced gastric damage in rats. Biotech Histochem, 2023;98(6):1-8.
Blanco LP, Pedersen H L, Wang X, Lightfoot YL, Seto N, Carmona‐Rivera C, et al. Improved mitochondrial metabolism and reduced inflammation following attenuation of murine lupus with coenzyme Q10 analog idebenone. Arthritis Rheumatol. 2020;72(3):454-464.
Calik I, Yayla M, Cinar I, Cadirci E, Albayrak A, Sirin B, et al. LP44 (4-[2 (methylthio)phenyl]-N-(1,2,3,4- tetrahydronaphthalen-1-yl)-1-piperazinehexanamide ) exerts anti-ulcer effects via 5-hydroxytryptamine receptor 7 activation on indomethacin-induced gastric ulcers in rats. Inflammopharmacolog y. 2020;28:893- 902.
Chandra P, Sachan N. Evaluation of mechanism(s) of action underlying the antioxidant and antiulcer activity of Sesamum indicum leaves extract in experimental rats. Indian J Pharmacol. 2022;54(6):423-430.
Clementi ME, Pizzoferrato M, Bianchetti G, Brancato A, Sampaolese B, Maulucci G, et al. Cytoprotective effect of idebenone through modulation of the intrinsic mitochondrial pathway of apoptosis in human retinal pigment epithelial cells exposed to oxidative stress induced by hydrogen peroxide. Biomedicines. 2022 (in press).
Choi Y, Cho YL, Park S, Park M, Hong KS, Park YJ, et al. Anti-Inflammatory Effects of Idebenone Attenuate LPS-Induced Systemic Inflammatory Diseases by Suppressing NF-kappaB Activation. Antioxidants (Basel). 2024 (in press).
Da Silva DM, Martins JLR, De Oliveira DR, Florentino IF, Da Silva DPB, Dos Santos FCA, et al. Effect of allantoin on experimentally induced gastric ulcers: pathways of gastroprotection. Eur J Pharmacol. 2018;821:68-78.
El-Gendy ZA, Taher RF, Elgamal AM, Serag A, Hassan A, Jaleel GAA, et al. Metabolites profiling and bioassays reveal bassia indica ethanol extract protective effect against stomach ulcers development via HMGB1/TLR- 4/NF-kappaB pathway. Antioxidants. 2023 (in press).
Eraslan E, Tanyeli A, Guler MC, Kurt N, Yetim Z. Agomelatine prevents indomethacin-induced gastric ulcer in rats. Pharmacol Rep. 2020;72:984-991.
Fadda LM, Hagar H, Mohamed AM, Ali HM. Quercetin and idebenone ameliorate oxidative stress, inflammation, DNA damage, and apoptosis induced by titanium dioxide nanoparticles in rat liver. Dose Response. 2018 (in press).
Fischer S, Neun O, Rüsseler M, Herrmann E, Schippers P, Münzberg M, et al. Female sex as a negative predictor of outcomes of ankle arthrodesis: a retrospective comparative monocentric study. J Orthop Surg Res. 2024 (in press).
Gou T, Jin X, Xia J. Idebenone reduces sepsis-induced oxidative stress and apoptosis in hepatocytes via RAGE/ p38 signaling. Ann Transl Med. 2022;10(24):1363.
Gueven N, Ravishankar P, Eri R, Rybalka E. Idebenone: when an antioxidant is not an antioxidant. Redox Biol. 2021 (in press).
Hambardzumyan K, Hermanrud C, Marits P, Vivar N, Ernestam S, Wallman JK, et al. Association of female sex and positive rheumatoid factor with low serum infliximab and anti-drug antibodies, related to treatment failure in early rheumatoid arthritis: results from the SWEFOT trial population. Scand J Rheumatol. 2019 (in press).
Isnain FS, Liao NC, Tsai HY, Zhao YJ, Huang CH, Hsu JL, et al. Freshwater clam extract attenuates indomethacin-induced gastric damage in vitro and in vivo. Foods. 2022 (in press).
Jiang JX, Tomilov A, Montgomery C, Hui CK, Török NJ, Cortopassi G. Shc inhibitor idebenone ameliorates liver injury and fibrosis in dietary NASH in mice. J Biochem Mol Toxicol. 2021 (in press).
Jintao Y. Idebenone-loaded wound dressings promote diabetic wound healing through downregulation of IL1b, Nfkb genes and upregulation of Fgf2 gene. Res Vet Sci. 2022;151:128-137.
Karaoglan ES, Bayir Y, Albayrak A, Toktay E, Ozgen U, Kazaz C, et al. Isolation of major compounds and gastroprotective activity of alchemilla caucasica on indomethacin induced gastric ulcers in rats. Eurasian J Med. 2020;52(3):249-253.
Kosa P, Wu T, Phillips J, Leinonen M, Masvekar R, Komori M, et al. Idebenone does not inhibit disability progression in primary progressive MS. Mult Scler Relat Disord. 2020 (in press).
Kose D, Kose A, Halici Z, Cadirci E, Tavacı T, Gürbüz MA, et al. Bosentan, a drug used in the treatment of pulmonary hypertension, can prevent development of osteoporosis. Iran J Basic Med Sci. 2021;24(7):922- 927.
Kucukler S, Kandemir FM, Yildirim S. Protective effect of chrysin on indomethacin induced gastric ulcer in rats: role of multi-pathway regulation. Biotech & Histochem. 2022;97(7):490-503.
Kumar S, Gupta E, Kaushik S, Kumar Srivastava V, Mehta SK, Jyoti A. Evaluation of oxidative stress and antioxidant status: Correlation with the severity of sepsis. Scand J Immunol. 2018 (in press).
Ma N, Sun Y, Yi J, Zhou L, Cai S. Chinese sumac (Rhus chinensis Mill.) fruits alleviate indomethacin-induced gastric ulcer in mice by improving oxidative stress, inflammation and apoptosis. J Ethnopharmacol. 2022 (in press).
Mahmoud MF, Abdo W, Nabil M, Drissi B, El-Shazly AM, Abdelfattah MAO, et al. Apple (Malus domestica Borkh) leaves attenuate indomethacin-induced gastric ulcer in rats. Biomed Pharmacother. 2023 (in press).
Mahmoud MF, Nabil M, Abdo W, Abdelfattah MAO, El-Shazly AM, El Kharrassi Y, et al. Syzygium samarangense leaf extract mitigates indomethacin-induced gastropathy via the NF-κB signaling pathway in rats. Biomed Pharmacother. 2021 (in press).
Narayanan M, Reddy KM, Marsicano E. Peptic ulcer disease and helicobacter pylori infection. Mo Med, 2018;115(3):219-224.
Neamatallah T. Caff eic acid phenethyl ester attenuates indomethacin-induced gastric ulcer in rats, Naunyn Schmiedebergs Arch Pharmacol, 2024;397(3):1791- 1801.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-358.
Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative stress: harms and benefi ts for human health. Oxid Med Cell Longev. 2017 (in press).
Qi FX, Hu Y, Kang LJ, Li P, Gao TC, Zhang X. Eff ects of butyphthalide combined with idebenone on infl ammatory cytokines and vascular endothelial functions of patients with vascular dementia. J Coll Physicians Surg Pak. 2020;30(1): 23-27.
Sedlak J, Lindsay RH. Estimation of total, proteinbound, and nonprotein sulfhydryl groups in tissue with ellman's reagent. Anal Biochem. 1968;25:192-205.
Shahzad N, Anjum I, Ahsan H, Alamgeer Syed SK, Mushtaq MN. Gastroprotective potential and mechanisms of action of Hedera nepalensis. Braz J Pharm Sci 2023 (in press).
Shastri S, Shinde T, Sohal SS, Gueven N, Eri R. Idebenone protects against acute murine colitis via antioxidant and anti-infl ammatory mechanisms. Int J Mol Sci. 2020;21(2):484.
Toktay E, Yayla M, Sahin L, Harmankaya A, Ozic C, Aksu Kilicle P, et al. The eff ects of dragon fruit (Hylocereus polyrhizus) extract on indomethacininduced stomach ulcer in rats. J Food Biochem. 2022 (in press).
Ugan RA, Un H. The protective roles of butein on indomethacin induced gastric ulcer in mice. Eurasian J Med. 2020;52(3):265-270.
Ugan RA, Un H, Kose D, Cadirci E, Bal Tastan T, Yayla M, et al. Can aprepitant used for nausea and vomiting be good gastrointestinal complaints? Naunyn Schmiedebergs Arch Pharmacol. 2020;393(12):2463- 2472.
Valduga AH, Mizobuti DS, Moraes FDSR, Mâncio RD, Moraes LHR, Hermes TA, et al. Protection of dystrophic muscle cells using Idebenone correlates with the interplay between calcium, oxidative stress and infl ammation. Int J Exp Pathol. 2023;104(1):4-12.
Yi L, Lu Y, Yu S, Cheng Q, Yi L. Formononetin inhibits infl ammation and promotes gastric mucosal angiogenesis in gastric ulcer rats through regulating NF-κB signaling pathway. J Recept Signal Transduct Res. 2022;42(1):16-22.
Zhang H, Wu H, Qi X, Wu F, Zhang D. Eff ect of butylphthalide combined with idebenone on vascular dementia: A retrospective observational analysis. Medicine (Baltimore). 2024 (in press).
Downloads
Published
Data Availability Statement
Not Informed
Issue
Section
License
Copyright (c) 2025 Brazilian Journal of Pharmaceutical Sciences

This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on-line journal has open and free access.