Implication of Nrf2/HO-1 pathway in the coloprotective effect of coenzyme Q10 against experimentally induced ulcerative colitis
- PMID: 28050757
- DOI: 10.1007/s10787-016-0305-0
Implication of Nrf2/HO-1 pathway in the coloprotective effect of coenzyme Q10 against experimentally induced ulcerative colitis
Abstract
Purpose: Given the increased incidence of ulcerative colitis worldwide, the current study was designed to investigate the coloprotective potential of CoQ10 against experimentally induced ulcerative colitis (UC) and specify the implicated mechanisms.
Methods: Ulcerative colitis was induced by intracolonic instillation of [2 ml, 3% v/v acetic acid (AA)]. Rats in the different experimental groups received CoQ10 (10 or 30 and 100 mg/kg, orally) for eight consecutive days, either in a protective or curative regimen.
Results: Intracolonic AA instillation significantly increased colon/body weight index, colon weight/colon length ratio, clinical evaluation and macroscopic scoring of UC, serum LDH, C-reactive protein and decreased the serum total antioxidant capacity. Colon MDA, TNF-α and calcium content significantly increased as well, with concomitant reduction in colon GSH, SOD, CAT, Nrf2 and HO-1 contents. Moreover, immunohistochemical staining of colon specimen revealed increased expression of caspase-3 with significant histopathological changes. Coenzyme Q10 suppressed the release of inflammatory biomarkers and restored oxidants/antioxidants hemostasis. In a dose-dependent manner, CoQ10 significantly decreased colon/body weight index, colon weight/colon length ratio, clinical evaluation and macroscopic scoring of UC, serum LDH, C-reactive protein, colon MDA, TNF-α, caspase-3 expression and increased the serum total antioxidant capacity. Colon GSH, SOD, CAT, Nrf2 and HO-1 contents significantly increased. Moreover, coenzyme Q10 significantly preserved tissue histopathological architecture. It appears that the coloprotective effect of CoQ10 was calcium-independent.
Conclusion: Coenzyme Q10 dose-dependently protects against AA-induced UC mainly via modulation of Nrf2/HO-1 and caspase-3 pathways. Antioxidant, anti-inflammatory and anti-apoptotic properties of CoQ10 are implicated in its observed therapeutic benefit.
Keywords: Caspase-3; Coenzyme Q10; HO-1; Nrf2; TNF-α; Ulcerative colitis.
Similar articles
-
Targeting Nrf2/HO-1 signaling by crocin: Role in attenuation of AA-induced ulcerative colitis in rats.Biomed Pharmacother. 2019 Feb;110:389-399. doi: 10.1016/j.biopha.2018.11.133. Epub 2018 Dec 5. Biomed Pharmacother. 2019. PMID: 30530041
-
Attenuating effects of coenzyme Q10 and amlodipine in ulcerative colitis model in rats.Immunopharmacol Immunotoxicol. 2015 Jun;37(3):244-51. doi: 10.3109/08923973.2015.1021357. Epub 2015 Mar 10. Immunopharmacol Immunotoxicol. 2015. PMID: 25753843
-
Olmesartan ameliorates chemically-induced ulcerative colitis in rats via modulating NFκB and Nrf-2/HO-1 signaling crosstalk.Toxicol Appl Pharmacol. 2019 Feb 1;364:120-132. doi: 10.1016/j.taap.2018.12.020. Epub 2018 Dec 27. Toxicol Appl Pharmacol. 2019. PMID: 30594690
-
Molecular mechanisms underlying the renal protective effects of coenzyme Q10 in acute kidney injury.Cell Mol Biol Lett. 2022 Jul 22;27(1):57. doi: 10.1186/s11658-022-00361-5. Cell Mol Biol Lett. 2022. PMID: 35869439 Free PMC article. Review.
-
The role of Nrf2 in the pathogenesis and treatment of ulcerative colitis.Front Immunol. 2023 Jun 5;14:1200111. doi: 10.3389/fimmu.2023.1200111. eCollection 2023. Front Immunol. 2023. PMID: 37359553 Free PMC article. Review.
Cited by
-
Rutin mitigates acetic acid-induced ulcerative colitis: novel coloprotective mechanism.Toxicol Res (Camb). 2024 Jul 25;13(4):tfae108. doi: 10.1093/toxres/tfae108. eCollection 2024 Aug. Toxicol Res (Camb). 2024. PMID: 39119265
-
Impact of Coenzyme Q10 Administration on Lead Acetate-Induced Testicular Damage in Rats.Oxid Med Cell Longev. 2020 Jun 2;2020:4981386. doi: 10.1155/2020/4981386. eCollection 2020. Oxid Med Cell Longev. 2020. PMID: 32566085 Free PMC article.
-
Jagged-1 attenuates LPS-induced apoptosis and ROS in rat intestinal epithelial cells.Int J Clin Exp Pathol. 2018 Aug 1;11(8):3994-4003. eCollection 2018. Int J Clin Exp Pathol. 2018. PMID: 31949788 Free PMC article.
-
A randomized controlled trial on the coloprotective effect of coenzyme Q10 on immune-inflammatory cytokines, oxidative status, antimicrobial peptides, and microRNA-146a expression in patients with mild-to-moderate ulcerative colitis.Eur J Nutr. 2021 Sep;60(6):3397-3410. doi: 10.1007/s00394-021-02514-2. Epub 2021 Feb 23. Eur J Nutr. 2021. Retraction in: Eur J Nutr. 2022 Sep;61(6):3313. doi: 10.1007/s00394-022-02949-1 PMID: 33620550 Retracted. Clinical Trial.
-
Brassica-Derived Plant Bioactives as Modulators of Chemopreventive and Inflammatory Signaling Pathways.Int J Mol Sci. 2017 Sep 1;18(9):1890. doi: 10.3390/ijms18091890. Int J Mol Sci. 2017. PMID: 28862664 Free PMC article. Review.
References
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Medical
Research Materials
Miscellaneous