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西替利嗪和氯雷他定通过调节PI3K/Akt/Nrf2信号通路及促炎细胞因子释放改善大鼠乙酸诱导的溃疡性结肠炎

Amelioration of acetic acid-induced ulcerative colitis in rats by cetirizine and loratadine via regulation of the PI3K/Akt/Nrf2 signalling pathway and pro-inflammatory cytokine release.

作者信息

Asaad Gihan F, Mostafa Rasha E

机构信息

Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt.

出版信息

Iran J Basic Med Sci. 2024;27(6):761-767. doi: 10.22038/IJBMS.2024.75889.16426.

DOI:10.22038/IJBMS.2024.75889.16426
PMID:38645494
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11024406/
Abstract

OBJECTIVES

Ulcerative colitis is a chronic inflammatory bowel disease (IBD) that causes inflammation and ulcers in the rectum and the innermost layer of the large intestine. Our study aimed to elucidate the ameliorative effect of cetirizine (CTZ) and loratadine (LOR) against acetic acid-induced ulcerative colitis in rats via assessment of the PI3K/p-Akt/Nrf2 signaling pathway and proinflammatory cytokine release.

MATERIALS AND METHODS

Thirty-two rats were allocated into four groups (n=8). Group (I) was considered normal control. Acetic acid (AA) was injected intrarectally in groups (2-4). Group (2) was kept untreated. Group (3) was administered CTZ (20 mg/kg/day) for 7 days. Group (4) was administered LOR (10 mg/kg/day) for 7 days.

RESULTS

AA showed severe macroscopic colonic lesions associated with increased ulcer number, area, and severity with significantly elevated PI3K, p-Akt, Nrf2, TNF-α, and IL-6 in colorectal tissue as compared to the normal control group. All the aforementioned indicators were greatly improved by CTZ and LOR therapy.

CONCLUSION

This is the first study to elucidate the ameliorative effect of CTZ and LOR against AA-induced UC in rats. CTZ and LOR treatment mitigates UC via amelioration of the PI3K/p-Akt/Nrf2 pathway and proinflammatory cytokine release.

摘要

目的

溃疡性结肠炎是一种慢性炎症性肠病(IBD),可导致直肠和大肠最内层发生炎症和溃疡。我们的研究旨在通过评估PI3K/p-Akt/Nrf2信号通路和促炎细胞因子释放,阐明西替利嗪(CTZ)和氯雷他定(LOR)对大鼠乙酸诱导的溃疡性结肠炎的改善作用。

材料与方法

将32只大鼠分为四组(n = 8)。第(I)组为正常对照组。第(2 - 4)组经直肠注射乙酸(AA)。第(2)组不进行治疗。第(3)组给予CTZ(20 mg/kg/天),持续7天。第(4)组给予LOR(10 mg/kg/天),持续7天。

结果

与正常对照组相比,AA显示出严重的结肠宏观病变,溃疡数量、面积和严重程度增加,结直肠组织中PI3K、p-Akt、Nrf2、TNF-α和IL-6显著升高。CTZ和LOR治疗使上述所有指标均有显著改善。

结论

这是第一项阐明CTZ和LOR对大鼠AA诱导的UC改善作用的研究。CTZ和LOR治疗通过改善PI3K/p-Akt/Nrf2通路和促炎细胞因子释放减轻UC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e63/11024406/b7850dc81fc7/IJBMS-27-761-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e63/11024406/91c87b8717a4/IJBMS-27-761-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e63/11024406/cc54a2552858/IJBMS-27-761-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e63/11024406/95336cbba806/IJBMS-27-761-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e63/11024406/b7850dc81fc7/IJBMS-27-761-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e63/11024406/91c87b8717a4/IJBMS-27-761-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e63/11024406/cc54a2552858/IJBMS-27-761-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e63/11024406/95336cbba806/IJBMS-27-761-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e63/11024406/b7850dc81fc7/IJBMS-27-761-g004.jpg

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Inflammatory Bowel Disease: Crosstalk between Histamine, Immunity, and Disease.炎症性肠病:组胺、免疫与疾病的串扰。
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