Estarreja João, Caldeira Gonçalo, Silva Inês, Mendes Priscila, Mateus Vanessa
H&TRC-Health and Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal.
iMed.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal.
JMIR Res Protoc. 2023 Nov 16;12:e48368. doi: 10.2196/48368.
Hemin is a commonly used drug in the treatment of acute attacks of porphyria, due to its capability of restoring normal levels of hemoproteins and respiratory pigments. In addition, this drug has demonstrated the capacity to induce the heme oxygenase (HO) enzyme. At the moment, there are 3 known HO isoenzymes in mammals: HO-1, HO-2, and HO-3. The first of these shows cytoprotective, antioxidant, and anti-inflammatory effects. Currently, medicines used in inflammatory disorders have increased toxicity, especially over longer time frames, which highlights the need to investigate new, safer options. Indeed, the current nonclinical evidence demonstrates the potential that hemin has a significant anti-inflammatory effect in several animal models of inflammation-related diseases, such as experimental colitis, without significant side effects. However, the underlying mechanism(s) are still not fully understood. In addition, past nonclinical studies have applied different therapeutic regimens, making it relatively difficult to understand which is optimal. According to the literature, there is a lack of review articles discussing this topic, highlighting the need for a summary and analysis of the available preclinical evidence to elucidate the abovementioned issues. Therefore, a qualitative synthesis of the current evidence is essential for the research and medical communities.
This systematic review aims to summarize and analyze currently available nonclinical data to ascertain the potential anti-inflammatory effect of hemin in animal models.
Throughout the development of this protocol, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The comprehensive search strategy will be carried out in MEDLINE (PubMed), Web of Science, and Scopus without any filters associated with publication date. Only in vivo, nonclinical studies that evaluated the potential anti-inflammatory effect of hemin will be included. The evaluated outcomes will be the observed clinical signs, inflammatory and other biochemical markers, and macroscopic and microscopic evaluations. To analyze the potential risk of bias, we will use the risk of bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE).
Currently, it is not possible to disclose any results since the project is still in initial steps. More specifically, we are currently engaged in the identification of eligible articles through the application of the inclusion and exclusion criteria. The work was initiated in April 2023, and it is expected to be finished at the end of 2023.
Concerning the major gap in the literature regarding the underlying mechanism(s) and treatment-related properties, this systematic review will be essential to clearly summarize and critically analyze the nonclinical data available, promoting a clearer vision of the potential anti-inflammatory effect of hemin.
PROSPERO CRD42023406160; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=406160.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48368.
氯高铁血红素是治疗卟啉症急性发作的常用药物，因其能够使血蛋白和呼吸色素水平恢复正常。此外，该药物已被证明具有诱导血红素加氧酶（HO）的能力。目前，哺乳动物中有3种已知的HO同工酶：HO-1、HO-2和HO-3。其中第一种表现出细胞保护、抗氧化和抗炎作用。目前，用于炎症性疾病的药物毒性增加，尤其是在较长时间内，这凸显了研究新的、更安全选择的必要性。事实上，目前的非临床证据表明，氯高铁血红素在几种炎症相关疾病的动物模型（如实验性结肠炎）中具有显著的抗炎作用，且无明显副作用。然而，其潜在机制仍未完全明确。此外，过去的非临床研究采用了不同的治疗方案，使得相对难以理解哪种方案是最佳的。根据文献，缺乏讨论该主题的综述文章，这凸显了对现有临床前证据进行总结和分析以阐明上述问题的必要性。因此，对现有证据进行定性综合对研究和医学界至关重要。
本系统评价旨在总结和分析目前可用的非临床数据，以确定氯高铁血红素在动物模型中的潜在抗炎作用。
在本方案的制定过程中，我们遵循系统评价和Meta分析的首选报告项目（PRISMA）方案。将在MEDLINE（PubMed）、科学网和Scopus中进行全面检索，不设置与出版日期相关的任何筛选条件。仅纳入评估氯高铁血红素潜在抗炎作用的体内非临床研究。评估的结果将是观察到的临床体征、炎症和其他生化标志物，以及宏观和微观评估。为了分析潜在的偏倚风险，我们将使用实验动物系统评价中心（SYRCLE）开发的偏倚风险工具。
由于该项目仍处于初始阶段，目前无法披露任何结果。更具体地说，我们目前正通过应用纳入和排除标准来识别符合条件的文章。这项工作于2023年4月开始，预计在2023年底完成。
鉴于文献中关于潜在机制和治疗相关特性的重大空白，本系统评价对于清晰总结和批判性分析现有非临床数据至关重要，有助于更清楚地了解氯高铁血红素的潜在抗炎作用。
PROSPERO CRD42023406160；https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=406160。
国际注册报告识别码（IRRID）：PRR1-10.2196/48368。
