A triterpenoid (corosolic acid) ameliorated AOM-mediated aberrant crypt foci in rats: modulation of Bax/PCNA, antioxidant and inflammatory mechanisms

IF 2.9 4区生物学 Q3 CELL BIOLOGY Journal of Molecular Histology Pub Date : 2024-08-10 DOI:10.1007/s10735-024-10229-x

Morteta H. Al-Medhtiy, Mohammed T Mohammed, Mohammed M. Hussein M. Raouf, Ayman M. Al-Qaaneh, Ahmed A.j. Jabbar, Fuad Othman Abdullah, Ramzi A. Mothana, Abdullah R. Alanzi, Rawaz Rizgar Hassan, Mahmood Ameen Abdulla, Musher Ismail saleh, Sidgi Hasson

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Abstract

Corosolic acid (CA) is a well-known natural pentacyclic triterpene found in numerous therapeutic plants that can exhibit many bioactivities including anti-inflammatory and anti-tumor actions. The current investigation explores the chemoprotective roles of CA against azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty Sprague Dawley rats were grouped in 5 cages; Group A, normal control rats inoculated subcutaneously (sc) with two doses of normal saline and fed orally on 10% tween 20; Groups B-E received two doses (sc) of azoxymethane in two weeks and treated with either 10% tween 20 (group B) or two intraperitoneal injections of 35 mg/kg 5-fluorouracil each week for one month (group C), while group D and E treated with 30 and 60 mg/kg, respectively, for 2 months. The toxicity results showed lack of any behavioral abnormalities or mortality in rats ingested with up-to 500 mg/kg of CA. The present AOM induction caused a significant initiation of ACF characterized by an increased number, larger in size, and well-matured tissue clusters in cancer controls. AOM inoculation created a bizarrely elongated nucleus, and strained cells, and significantly lowered the submucosal glands in colon tissues of cancer controls compared to 5-FU or CA-treated rats. CA treatment led to significant suppression of ACF incidence, which could be mediated by its modulatory effects on the immunohistochemical proteins (pro-apoptotic (Bax) and reduced PCNA protein expressions in colon tissues). Moreover, CA-treated rats had improved oxidative stress-mediated cytotoxicity indicated by increased endogenous antioxidants (SOD and CAT) and reduced lipid peroxidation indicators (MDA). In addition, CA ingestion (30 and 60 mg/kg) suppressed the inflammatory cascades, indicated by decreased serum TNF-α and IL-6 cytokines and increased anti-inflammatory (IL-10) cytokines consequently preventing further tumor development. CA treatment maintained liver and kidney functions in rats exposed to AOM cytotoxicity. CA could be a viable alternative for the treatment of oxidative-related human disorders including ACF.

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一种三萜类化合物（科罗索酸）可改善 AOM 介导的大鼠异常隐窝病灶：调节 Bax/PCNA、抗氧化和炎症机制。

科罗索酸（CA）是一种众所周知的天然五环三萜类化合物，存在于多种治疗植物中，具有多种生物活性，包括抗炎和抗肿瘤作用。目前的研究探讨了 CA 对偶氮甲烷（AOM）诱导的大鼠结肠异常隐窝（ACF）的化学保护作用。将 30 只 Sprague Dawley 大鼠分成 5 组，A 组为正常对照组，皮下注射两剂生理盐水（sc），口服 10% 吐温 20；B-E组大鼠在两周内接受两剂（sc）偶氮甲烷，并用10%吐温20（B组）或每周两次腹腔注射35毫克/千克5-氟尿嘧啶治疗一个月（C组），D组和E组分别用30毫克/千克和60毫克/千克治疗两个月。毒性结果表明，摄入高达 500 毫克/千克 CA 的大鼠没有出现任何行为异常或死亡。在癌症对照组中，目前的AOM诱导引起了明显的ACF，其特点是数量增加、体积增大和组织成熟。与5-FU或CA处理的大鼠相比，AOM接种造成了奇异的细胞核拉长和细胞紧张，并显著降低了癌症对照组大鼠结肠组织粘膜下腺体的数量。CA 能显著抑制 ACF 的发生，这可能是由于它对免疫组化蛋白（促凋亡蛋白（Bax）和减少结肠组织中 PCNA 蛋白的表达）有调节作用。此外，内源性抗氧化剂（SOD 和 CAT）的增加和脂质过氧化指标（MDA）的降低表明，CA 处理的大鼠改善了氧化应激介导的细胞毒性。此外，摄入 CA（30 和 60 mg/kg）可抑制炎症级联反应，表现为血清 TNF-α 和 IL-6 细胞因子减少，抗炎（IL-10）细胞因子增加，从而防止肿瘤进一步发展。CA 治疗可维持暴露于 AOM 细胞毒性的大鼠的肝脏和肾脏功能。CA 可以作为治疗与氧化有关的人类疾病（包括 ACF）的一种可行的替代疗法。

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.