Tetrylpyamethrazine alleviates hepatic fibrosis induced by experimental mansonic schistosomiasis.

IF 4.6 2区 医学 Q2 IMMUNOLOGY
Ana Carolina Campos Dos Santos, Daniel Figueiredo-Vanzan, Josiane Bentes, Juliana Maria Motta, Hilton Antônio Mata-Santos, Alexandre Dos Santos Pyrrho, Morgana Teixeira Lima Castelo-Branco
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Abstract

Hepatic fibrosis resulting from human mansonic schistosomiasis significantly impairs liver function and contributes substantially to morbidity associated with helminth infections. This pathological state develops following the deposition of helminth eggs within hepatic tissues, triggering a granulomatous inflammatory reaction. Schistosomiasis, a neglected tropical disease affecting approximately 240 million individuals globally, represents a major public health challenge. Although praziquantel (PZQ) is recommended by the World Health Organization (WHO) as the primary treatment for helminth infections, additional therapies are required to address the associated liver fibrosis. This study investigated the efficacy of tetramethylpyrazine (TMP), a natural compound known for its anti-inflammatory, antifibrotic, and hepatoprotective properties in various experimental models, in mitigating hepatic fibrosis induced by mansonic schistosomiasis. Our in vivo experiments demonstrated that TMP treatment significantly reduced hepatic granuloma size, as evidenced by histological analysis. Furthermore, our in vitro studies showed that TMP increased levels of the anti-inflammatory cytokine IL-10 while decreasing levels of the profibrotic cytokine IL-13 in a concentration-dependent manner. Immunofluorescence analysis also revealed that TMP effectively inhibited collagen deposition. Collectively, these findings suggest that TMP exhibits potential as an anti-inflammatory and antifibrotic agent for hepatic fibrosis resulting from Schistosoma mansoni infection.

四甲基吡嗪对实验性血吸虫病肝纤维化的缓解作用。
由人血吸虫病引起的肝纤维化严重损害肝功能,并导致与寄生虫感染相关的发病率。这种病理状态是在蠕虫卵在肝脏组织内沉积后发生的,引发肉芽肿性炎症反应。血吸虫病是一种被忽视的热带疾病,影响全球约2.4亿人,是一项重大的公共卫生挑战。尽管吡喹酮(PZQ)被世界卫生组织(WHO)推荐作为蠕虫感染的主要治疗方法,但需要额外的治疗来解决相关的肝纤维化。本研究研究了川芎嗪(tetramethylpyrazine, TMP)的疗效,川芎嗪是一种天然化合物,在各种实验模型中具有抗炎、抗纤维化和肝保护特性,可减轻人血吸虫病引起的肝纤维化。我们的体内实验表明,经组织学分析证实,TMP治疗可显著减少肝脏肉芽肿的大小。此外,我们的体外研究表明,TMP增加了抗炎细胞因子IL-10的水平,同时以浓度依赖的方式降低了促纤维化细胞因子IL-13的水平。免疫荧光分析也显示TMP有效抑制胶原沉积。总的来说,这些发现表明TMP具有抗炎和抗纤维化的潜力,可用于治疗由曼氏血吸虫感染引起的肝纤维化。
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来源期刊
Inflammopharmacology
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 [...]
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