Ferrous sulfate, but not iron polymaltose complex, aggravates local and systemic inflammation and oxidative stress in dextran sodium sulfate-induced colitis in rats

Abstract

Background and aimsIron deficiency is common in inflammatory bowel disease, yet oral iron therapy may worsen the disease symptoms and increase systemic and local oxidative stress. The aim of this study was to compare the effects of oral ferrous sulfate and iron polymaltose complex on inflammatory and oxidative stress markers in colitic rats.MethodsAnimals were divided into four groups with ten animals each. Rats of three groups received dextran sodium sulfate to induce colitis and animals of two of these groups received 5 mg iron/kg of body weight a day, as ferrous sulfate or iron polymaltose complex, for 7 days. Gross colon anatomy, histology of colon and liver, stainings of L-ferritin, Prussian blue, hepcidin, tumor necrosis factor-α, and interleukin-6, as well serum levels of liver enzymes, inflammatory markers, and iron markers, were assessed.ResultsBody weight, gross anatomy, crypt injury and inflammation scores, inflammatory parameters in liver and colon, as well as serum and liver hepcidin levels were not significantly different between colitic animals without iron treatment and colitic animals treated with iron polymaltose complex. In contrast, ferrous sulfate treatment caused significant worsening of these parameters. As opposed to ferrous sulfate, iron polymaltose complex caused less or no additional oxidative stress in the colon and liver compared to colitic animals without iron treatment.ConclusionIron polymaltose complex had negligible effects on colonic tissue erosion, local or systemic oxidative stress, and local or systemic inflammation, even at high therapeutic doses, and may thus represent a valuable oral treatment of iron deficiency in inflammatory bowel disease.

Supercritical Fluid Extract of Angelica sinensis and Zingiber officinale Roscoe Ameliorates TNBS-Induced Colitis in Rats

“…To some extent, our results support the explanation that the higher hepcidin level in TNBS group is the consequence of the more severe inflammation state, as Toblli et al described [47]. Administration of AZ-SFE and mesalazine decreased the production of hepcidin, indicating the potency of AZ-SFE on the regulation of iron homeostasis.…”

Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate)

“…paracellular pathway [ 62 ], transcellular pathway [ 63 ], gut microbiota [ 64 ]) have not been excluded (T. Ganz, private oral communication, March 4, 2019 [manuscript in preparation]). Of further interest is that ferric iron, such as in Auryxia and unlike ferrous iron, is not easily oxidized [ 65 ]. Ferrous iron, during oxidation, can catalyze the formation of free radicals, causing GI mucosal cell damage and erosions of the GI mucosa that likely account for the reported increased incidence of GI adverse effects with ferrous iron compared with ferric iron products (Fig.…”

“…Ferrous iron, during oxidation, can catalyze the formation of free radicals, causing GI mucosal cell damage and erosions of the GI mucosa that likely account for the reported increased incidence of GI adverse effects with ferrous iron compared with ferric iron products (Fig. 4 ) [ 65 – 71 ].

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Protective effects of myristicin against ulcerative colitis induced by acetic acid in male mice

“…Conversely, the proinflammatory cytokines cause oxidative stress by promoting the release of ROS from immune and non-immune cells (Reifen, Nissenkorn, Matas, & Bujanover, 2004). Thus, uncontrolled inflammation and oxidative stress are involved in the spiralling vicious cycle that contributes to the severity of intestinal inflammation (Toblli, Cao, & Angerosa, 2015). Therefore, it is not surprising that natural antioxidant drugs (like Myr) inhibited NF-κB activation.…”