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对异丙基甲苯(对伞花烃)单独及与奎宁联合使用通过调节炎症和氧化应激对疟疾感染的治疗作用

Therapeutic Effects of Isopropyltoluene (p-Cymene) Alone and in Combination with Quinine Against Malaria Infection Through Modulation of Inflammation and Oxidative Stress.

作者信息

Shater Abdullah F

机构信息

Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.

出版信息

Vector Borne Zoonotic Dis. 2025 Jul 29. doi: 10.1177/15303667251363381.

DOI:10.1177/15303667251363381
PMID:40729099
Abstract

This study aims to evaluate the therapeutic effects and potential mechanisms of p-cymene (CM) alone and in combination with quinine (Qu) against -infected mice. A total of 108 BALB/c mice were randomly divided into nine groups included six infected groups, which received normal saline, Qu (10 mg/kg), CM 5 mg/kg, CM 10 mg/kg, CM (5 mg/kg) + Qu (10 mg/kg), and CM (10 mg/kg) + Qu (10 mg/kg) as well as three noninfected groups, which received normal saline, CM 5 mg/kg, and CM 10 mg/kg. Mice were intraperitoneally infected by 1 × 10 malaria-infected erythrocytes. Infected mice were orally treated daily over a period of 4 days. Then parasite growth suppression (PGS), survival rate, the level of oxidant and antioxidant markers, and analysis of immune response-related genes were also evaluated. The highest survival rate of 100% was observed in infected mice treated with a combination of CM and Qu, which also demonstrated a PGR value of 100% ( < 0.001). The combination of CM and Qu resulted in the most significant reductions in tissue concentrations of malondialdehyde and nitric oxide, while upregulating the expression of the superoxide dismutase, glutathione peroxidase, and interleukin-(IL)10 (>fourfold change) genes resulted in a reduction in the expression level of the tumor necrosis factor (<1.3-fold-change) and IL-1β (<1.4-fold change) genes. The combination of CM and Qu also caused significant modulation of serum levels of liver and kidney markers in malaria-infected mice. The results of this survey indicate that the combination therapy of CM with Qu demonstrates significant effectiveness in treating malaria-infected mice by regulating oxidative stress, enhancing antioxidant enzyme activity, and modulating inflammatory responses. However, to further validate the therapeutic potential of this compound, it is essential to conduct clinical trials that evaluate both its toxicity and therapeutic efficacy.

摘要

本研究旨在评估对伞花烃(CM)单独及与奎宁(Qu)联合使用对感染小鼠的治疗效果及潜在机制。总共108只BALB/c小鼠被随机分为9组,其中6个感染组分别接受生理盐水、奎宁(10 mg/kg)、对伞花烃5 mg/kg、对伞花烃10 mg/kg、对伞花烃(5 mg/kg)+奎宁(10 mg/kg)、对伞花烃(10 mg/kg)+奎宁(10 mg/kg),另外3个未感染组分别接受生理盐水、对伞花烃5 mg/kg、对伞花烃10 mg/kg。小鼠通过腹腔注射1×10 个感染疟原虫的红细胞进行感染。感染小鼠连续4天每日接受口服治疗。然后评估寄生虫生长抑制(PGS)、存活率、氧化剂和抗氧化剂标志物水平以及免疫反应相关基因分析。在用对伞花烃和奎宁联合治疗的感染小鼠中观察到最高存活率为100%,其PGR值也为100%(<0.001)。对伞花烃和奎宁的联合使用使丙二醛和一氧化氮的组织浓度显著降低,同时超氧化物歧化酶、谷胱甘肽过氧化物酶和白细胞介素-(IL)10(>4倍变化)基因的表达上调,导致肿瘤坏死因子(<1.3倍变化)和IL-1β(<1.4倍变化)基因的表达水平降低。对伞花烃和奎宁的联合使用还显著调节了疟疾感染小鼠血清中肝和肾标志物的水平。本次研究结果表明对伞花烃与奎宁联合治疗通过调节氧化应激、增强抗氧化酶活性和调节炎症反应,在治疗疟疾感染小鼠方面显示出显著效果。然而,为了进一步验证该化合物的治疗潜力,进行评估其毒性和治疗效果的临床试验至关重要。

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