Hemin Ameliorates the Inflammatory Activity in the Inflammatory Bowel Disease: A Non-Clinical Study in Rodents

Abstract

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Currently, there is no cure, and pharmacological treatment aims to induce and maintain remission in patients, so it is essential to investigate new possible treatments. Hemin is a heme-oxygenase inducer which can confer anti-inflammatory, cytoprotective, and antiapoptotic effects; therefore, it can be considered an asset for different gastrointestinal pathologies, namely for IBD. Aim: This experiment aims to evaluate the efficacy and safety of hemin, in a chronic 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rodents. Methods: The induction of chronic colitis consisted of five weekly intrarectal administrations of 1% TNBS. Then, the mice were treated daily with 5 mg/kg/day or 10 mg/kg/day of hemin, through intraperitoneal injections, for 14 days. Results: Hemin demonstrated an anti-inflammatory effect through the reduction in tumor necrosis factor (TNF)-α levels, fecal calprotectin, and fecal hemoglobin. It was also found to be safe in terms of extraintestinal manifestations, since hemin did not promote renal and/or hepatic changes. Conclusions: Hemin could become an interesting tool for new possible pharmacological approaches in the management of IBD.

Alleviative Role of Hemin on Reproductive Functions of Adult Male Rats Treated with Copper Oxide Nanoparticles

“…The improvement of H in the weight could be attributed to the decrement in MDA content which increased by CuO NPs or to the antioxidant property of H (Ali et al, 2019). Silva et al (2022) disagreed with these findings and reported that H did not show any apparent impact on the animals' body weight.…”

The Pharmacological Effect of Hemin in Inflammatory-Related Diseases: Protocol for a Systematic Review

“…RenderX pharmacological approach to treatment of inflammatory-related diseases, considering its efficacy and safety over the short or long term. Indeed, several nonclinical studies have already demonstrated that hemin has a significant anti-inflammatory effect in different contexts, such as in inflammatory bowel disease [2,6,16,17], kidney dysfunction [18][19][20], sepsis [21][22][23], arthritis [24,25], pancreatitis [26][27][28], cardiac infarction [29], and airway inflammation [30][31][32].…”

“…However, the administration of hemin can also induce the expression of the heme oxygenase (HO) enzyme, which is known as a rate-limiting enzyme for heme catabolism and is responsible for the production of biliverdin, free iron, and carbon monoxide [2,6,7]. Currently, there are 3 identified HO isoenzymes in mammals: HO-1, HO-2, and HO-3 [2,6]. HO-1 is expressed as a response to tissue damage and demonstrates cytoprotective action capable of inhibiting the inflammatory response and oxidative stress [8].…”

“…On the other hand, the HO-2 and HO-3 isoenzymes are expressed constitutively in tissues involved in heme catabolism, which regulates the normal functioning of cells [7,9]. Considering the nonclinical evidence currently available, it has been suggested that HO-1 concentration and HO-1 mRNA are significantly elevated in cases of inflammation, such as in active ulcerative colitis [2,6,10]. In fact, through histological studies, it has been observed that HO-1 expression occurs mainly in macrophages; however, it can also be found in epithelial cells when there is an inflammatory response [11,12].…”

Editorial: Novel Therapeutic Approaches in Inflammatory Bowel Diseases

“…Importantly, Hemin was deemed safe in terms of extraintestinal manifestations, showing no adverse effects on the kidneys or liver. As a result, the authors concluded that Hemin treatment could represent a novel pharmacological approach to managing IBD [ 6 ]. Kim and colleagues evaluated the effectiveness of inhibiting Sirtuin 7 (SIRT7) in a colitis mouse model.…”