Abstract
The environmental factors and genetic vulnerability trigger the inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn’s disease. Furthermore, the oxidative stress and inflammatory cytokines have been implicated in the aggravation of the IBDs. The aim of the present study was to investigate the effect of N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (NCHDH and NTHDH) compounds against the DSS-induced colitis in mice. The colitis was induced by 5% dextran sulfate sodium (DSS) dissolved in normal saline for 5 days. The effect of the NCHDH and NTHDH on the behavioral, biochemical, histological, and immunohistological parameters was assessed. The NCHDH and NTHDH treatment improved the behavioral parameters such as food intake, disease activity index, and diarrhea score significantly compared to DSS control. The NCHDH and NTHDH treatments significantly increased the antioxidant enzymes, whereas oxidative stress markers were markedly reduced. Similarly, the NCHDH and NTHDH treatments significantly suppressed the activity of nitric oxide (NO), myeloperoxidase (MPO), and eosinophil peroxidase (EPO). The histological studies showed a significant reduction in inflammation, immune cell infiltration, and fibrosis in the NCHDH- and NTHDH-treated groups. The immunohistochemical results demonstrated that NCHDH and NTHDH treatments markedly increase the expression level of Nrf2, HO-1 (hemeoxygenase-1), TRX (thioredoxin reductase), and IκB compared to the DSS-induced group. In the same way, the NCHDH and NTHDH significantly reduced the NF-κB and COX-2 (cyclooxygenase-2) expression levels. The NCHDH and NTHDH treatment significantly improved the symptoms associated with colitis via inducing antioxidants and attenuating oxidative stress markers.
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10 January 2024
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s00210-024-02942-x
Abbreviations
- IBD:
-
Inflammatory bowel diseases
- Nrf2:
-
Nuclear factor erythroid 2-related factor 2
- TNF-α:
-
Tumor necrosis factor-α
- COX-2:
-
Cyclooxygenase-2
- NF-κB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- GST:
-
Glutathione-S-transferases
- ARE:
-
Antioxidant response element
- CTAB:
-
Cetyltrimethylammonium bromide
- MPO:
-
Myeloperoxidase
- NO:
-
Nitric oxide
- SOD:
-
Sulfur oxide dismutase
- POD:
-
Peroxidase
- LPO:
-
Lipid peroxidase
- EPO:
-
Eosinophil peroxidase
- HO-1:
-
Hemeoxygenase-1
- PAS:
-
Periodic acid-Schiff
- MDA:
-
Malondialdehyde
- DSS:
-
Dextran sodium sulfate
- TRX:
-
Thioredoxin reductase
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This work was assisted by Higher Education Commission (HEC), Pakistan, through HEC indigenous scholarship with funding (No. 518–85883-2MD5-039 (50043702)).
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AUK, AK, and BS performed the animal’s activities and biochemical analysis. SA and AUK performed the computational analysis. AZ, MNA, and ZUR synthesized and characterized the compounds. AUK and MUA revised the manuscript. Salman Khan drafted the manuscript and supervised the project. All authors read and approved the manuscript. All the data were generated in-house and that no paper mill was used.
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Khan, A., Khan, A., Shal, B. et al. RETRACTED ARTICLE: Ameliorative effect of two structurally divergent hydrazide derivatives against DSS-induced colitis by targeting Nrf2 and NF-κB signaling in mice. Naunyn-Schmiedeberg's Arch Pharmacol 395, 1167–1188 (2022). https://doi.org/10.1007/s00210-022-02272-w
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DOI: https://doi.org/10.1007/s00210-022-02272-w