Combinatorial intervention with dental pulp stem cells and sulfasalazine in a rat model of ulcerative colitis.

IF 4.6 2区医学 Q2 IMMUNOLOGY Inflammopharmacology Pub Date : 2024-12-01 Epub Date: 2024-07-29 DOI:10.1007/s10787-024-01532-w

Riham M Aly, Rehab S Abohashem, Hanaa H Ahmed, Alyaa S Abdel Halim

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Abstract

Background: Ulcerative colitis is an inflammatory bowel disease (IBD) that involves inflammation of the colon lining and rectum. Although a definitive cure for IBD has not been identified, various therapeutic approaches have been proposed to mitigate the symptomatic presentation of this disease, primarily focusing on reducing inflammation. The aim of the present study was to evaluate the therapeutic potential of combining dental pulp stem cells (DPSCs) with sulfasalazine in an acetic acid-induced ulcerative colitis rat model and to assess the impact of this combination on the suppression of inflammatory cytokines and the regulation of oxidative stress in vivo.

Methods: Ulcerative colitis was induced in rats through transrectal administration of 3% acetic acid. The therapeutic effect of combining DPSCs and sulfasalazine on UC was evaluated by measuring the colonic weight/length ratio and edema markers; performing histopathological investigations of colon tissue; performing immunohistochemical staining for NF-κB-P65 and IL-1β; and evaluating oxidative stress and antioxidant indices via ELISA. Moreover, the proinflammatory markers NF-κB-P65, TNF-α and TLR-4 were assessed in colon tissue via ELISA. Furthermore, qRT‒PCR was used to estimate the expression levels of the TLR-4, NF-κB-P65, and MYD88 genes in colon tissue.

Results: The investigated macroscopic and microscopic signs of inflammation were markedly improved after the combined administration of sulfasalazine and DPSCs, where a noticeable improvement in histological structure, with an intact mucosal epithelium and mild inflammatory infiltration in the mucosa and submucosa, with slight hemorrhage. The administration of either DPSCs or sulfasalazine, either individually or in combination, significantly reduced ROS levels and significantly increased XOD activity. The immunohistochemical results demonstrated that the combined administration of DPSCs and sulfasalazine attenuated NFκB-p65 and IL-1β expression. Finally, the combined administration of DPSCs and sulfasalazine significantly downregulated MyD88, NF-κB and TLR4 gene expression.

Conclusions: Cotreatment with DPSCs and sulfasalazine had synergistic effects on ulcerative colitis, and these effects were relieved.

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牙髓干细胞和柳氮磺胺吡啶联合干预溃疡性结肠炎大鼠模型。

背景：溃疡性结肠炎是一种炎症性肠病（IBD），涉及结肠内膜和直肠的炎症。虽然尚未找到彻底治愈 IBD 的方法，但已提出了各种治疗方法来减轻这种疾病的症状表现，主要侧重于减轻炎症。本研究旨在评估牙髓干细胞（DPSCs）与柳氮磺吡啶结合在醋酸诱导的溃疡性结肠炎大鼠模型中的治疗潜力，并评估这种结合对抑制体内炎症细胞因子和调节氧化应激的影响：方法：通过经直肠给药 3% 乙酸诱发大鼠溃疡性结肠炎。通过测量结肠重量/长度比和水肿指标、结肠组织病理学检查、NF-κB-P65 和 IL-1β 免疫组化染色以及通过 ELISA 评估氧化应激和抗氧化指标，评估了 DPSCs 和磺胺吡啶联合应用对 UC 的治疗效果。此外，还通过 ELISA 评估了结肠组织中的促炎标志物 NF-κB-P65、TNF-α 和 TLR-4。此外，还采用 qRT-PCR 技术估算结肠组织中 TLR-4、NF-κB-P65 和 MYD88 基因的表达水平：结果：联合应用柳氮磺胺吡啶和 DPSCs 后，所调查的炎症宏观和微观症状均得到明显改善，组织学结构明显改善，粘膜上皮完整，粘膜和粘膜下层有轻度炎症浸润，并伴有轻微出血。单独或联合使用 DPSCs 或柳氮磺胺吡啶均可显著降低 ROS 水平，并显著提高 XOD 活性。免疫组化结果表明，联合使用 DPSCs 和柳氮磺胺吡啶可减少 NFκB-p65 和 IL-1β 的表达。最后，DPSCs和磺胺吡啶联合用药可显著下调MyD88、NF-κB和TLR4基因的表达：结论：DPSCs和柳氮磺胺吡啶联合治疗对溃疡性结肠炎有协同作用，而且这些作用可以得到缓解。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]