JMIR Publications

ABSTRACT

Background:

Hemin is a commonly used drug in the treatment of acute attacks of porphyria, due to its capability of restoring the normal levels of hemoproteins and respiratory pigments. Currently, it is also known as an inducer of the heme-oxygenase (HO) enzyme. There are three HO isoenzymes in mammals, such as HO-1, -2, and -3, where the first one shows to have cytoprotective, antioxidant, and anti-inflammatory effects. Indeed, the non-clinical evidence seems to demonstrate an anti-inflammatory effect of hemin, however, there are several experimental studies using different protocols of treatment in animal models of inflammatory diseases. Although the fact there is already information regarding the potential anti-inflammatory effect of hemin, the underlying mechanism(s) remain unclear. In fact, it is possible to observe an absence of review articles in the literature that debate this topic.

Objective:

This systematic review aims to analyze and synthetize the non-clinical data currently available regarding the pharmacological effect of hemin in inflammatory-related diseases.

Methods:

Throughout the development of this protocol, it was followed the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols. The comprehensive search strategy will be conducted in MEDLINE (Pubmed), Web of Science, and Scopus, without any filters associated with language and time. Only non-clinical studies in vivo will be included, where it was evaluated the potential anti-inflammatory effect of hemin. The evaluated outcomes will be the observed clinical signs, inflammatory and other biochemical markers, as well as macroscopical and microscopical evaluations. In order to evaluate the internal validity of the selected studies, it will be considered the ARRIVE guideline checklist. Furthermore, to analyze the potential risk of bias, it will be used the SYRCLE’s risk of bias tool.

Results:

Currently, it is not possible to disclose any results since the project is still on the initial steps, more specifically, in the identification of eligible articles, through the application of the inclusion and exclusion criteria. In addition, this project has no funding, and it is being developed by a pharmacologist team. The work was initiated in April 2023 and it is expected to be released in October 2023.

Conclusions:

The current pharmacological approaches applied in chronic inflammatory diseases presents several side-effects due to their long-term toxicity, emphasizing the necessity of investigate new options for the future. Considering the preclinical evidence available, hemin arises as an interesting approach to be studied since it already demonstrated a significant anti-inflammatory effect in several inflammation-related disorders. 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 critical analyze the non-clinical data available, promoting a clearer vision on the potential anti-inflammatory effect of hemin. Clinical Trial: PROSPERO registration number: CRD42023406160.