维甲酸增强骨髓间充质干细胞(BM-MSCs)对大鼠顺铂诱导的肝毒性的治疗效果

IF 2.3 Q3 PHARMACOLOGY & PHARMACY Scientia Pharmaceutica Pub Date : 2022-09-29 DOI:10.3390/scipharm90040058
Maha M. Azzam, Abdelaziz M. Hussein, Basma H. Marghani, N. Barakat, M. Khedr, Nabil Abu Heakel
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引用次数: 4

摘要

(1) 背景:肝毒性是一种常见的健康问题,氧化应激在其潜在机制中起着至关重要的作用。我们观察了维甲酸(RA)在增强骨髓间充质干细胞(BM-MSCs)对顺铂(Cis)诱导的肝毒性的肝保护作用中的可能作用。(2) 方法:将60只雄性Sprague-Dawley大鼠(SD)随机分为6个主要相等的组:(1)对照组,(2)Cis组(大鼠腹腔注射Cis 7mg/Kg),(3)Cis+载体组(作为第2组,但大鼠接受BM-MSCs(载体)培养基)。,和(6)Cis和BM-MSC作为第3组,RA作为第4组。通过测量肝酶(ALT、AST)来评估肝损伤,而通过组织病理学检查来评估肝毒性。免疫组化检测凋亡标志物胱天蛋白酶-3蛋白。实时PCR检测转录水平的NADPH氧化酶和TNF-α。采用MDA、GSH和过氧化氢酶比色法测定氧化应激。(3) 结果:与Cis组相反(p<0.05),补充骨髓间充质干细胞/RA可显著降低血清ALT、AST等肝损伤指标和MDA等氧化应激标志物的水平,增加肝脏GSH、过氧化氢酶,降低TNF-α的表达和下调NADPH氧化酶。骨髓间充质干细胞/RA治疗后的改善通过组织病理学检查得到证实。此外,免疫组织化学研究证实了骨髓间充质干细胞/RA治疗后肝组织中胱天蛋白酶-3的下调。(4) 结论:骨髓间充质干细胞和RA通过下调氧化应激导致抗炎TNF-α和凋亡胱天蛋白酶-3的调节,减轻了Cis诱导的肝毒性,表明其在肝毒性中具有良好的作用。
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Retinoic Acid Potentiates the Therapeutic Efficiency of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) against Cisplatin-Induced Hepatotoxicity in Rats
(1) Background: Hepatotoxicity is a common health problem, and oxidative stress plays a crucial role in its underlying mechanisms. We inspected the possible effect of retinoic acid (RA) in the potentiation of hepatoprotective effect of bone marrow mesenchymal stem cells (BM-MSCs) against Cisplatin (Cis)-induced hepatotoxicity. (2) Methods: 60 male Sprague Dawley rats (SD) were separated randomly and designated to six main equal groups as follows: (1) Control group, (2) Cis group (rats got Cis 7 mg/Kg i.p.), (3) Cis + vehicle group (as group 2, but rats received the (vehicle) culture media of BM-MSCs), (4) Cis as in group 2 + BM-MSCs (1x106), (5) Cis as for group 2 + RA 1 mg/Kg i.p., and (6) Cis and BM-MSCs as for group 3 + RA as for group 4. Liver injury was assessed by measuring liver enzymes (ALT, AST), while liver toxicity was evaluated by histopathological examination. Apoptotic marker caspase-3 protein was detected immunohistochemically. Real time PCR was performed to detect NADPH oxidase and TNF-α at transcription levels. Oxidative stress was investigated by colorimetric measurement of MDA, GSH and catalase. (3) Results: Contrary to the Cis group (p < 0.05), BM-MSCs/RA supplementation resulted in a substantial decrease in serum levels of hepatic impairment indicators such as ALT, AST and oxidative stress markers such as MDA, as well as an increase in hepatic GSH, Catalase, and a decrease in expression of TNF-α and downregulation of NADPH oxidase. The improvement after therapy with BM-MSCs/RA was confirmed by histopathological examination. Moreover, the downregulation of caspase-3 in liver tissue after BM-MSCs/RA treatment was validated by immunohistochemistry investigation. (4) Conclusions: BM-MSCs and RA attenuated Cis induced hepatotoxicity through downregulation of oxidative stress resulted in modulation of anti-inflammatory TNF-α and apoptosis caspase-3 indicating a promising role in hepatotoxicity.
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来源期刊
Scientia Pharmaceutica
Scientia Pharmaceutica Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
4.60
自引率
4.00%
发文量
67
审稿时长
10 weeks
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