Thiadiazolidinone-8 Ameliorates Inflammation Associated with Experimental Colitis in Mice

Mateus, Vanessa; Rocha, José Antonio; Alves, Paula; Mota-Filipe, Hélder; Sepodes, Bruno; Pinto, Rui

doi:10.1159/000471808

Cited by 12 publications

(20 citation statements)

References 33 publications

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“…This data is consistent with other previous findings, where anti-inflammatory drugs are able to decrease ALP level. 17 , 31 , 34 Furthermore, as intestinal ALP is expressed on the enterocytes and it is responsible for the mucosal defense, 35 , 36 our findings also suggest that hemin had a cytoprotective effect on the intestinal mucosa.…”

Section: Discussionsupporting

confidence: 53%

“…In our study, the intensity of hemorrhagic focus was evaluated by the fecal hemoglobin concentration. 17 , 31 We observed that hemin treatment produced a considerable influence in the intensity of hemorrhagic focus, because the fecal hemoglobin concentration significantly decreased in a dose-dependent manner after a daily dose of hemin. This finding suggests that hemin-treated mice presented an amelioration of the active inflammatory disease identified in mice with TNBS-induced colitis.…”

Section: Discussionmentioning

confidence: 79%

“…MPO activity was used as an index of quantitative inflammation and neutrophil infiltration in tissues. 17 , 31 , 37 Hemin administration was able to attenuate neutrophil infiltration and inflammation with both hemin doses, in a dose-dependent manner. However, a statistical significance difference was only identified in the highest hemin dose, where MPO decreased around 60% compared with the nontreated mice.…”

Section: Discussionmentioning

confidence: 93%

“…TNF-α and IL-1β are proinflammatory cytokines that can become dysregulated under pathologic condition of inflammation. 40 Actually, mice with TNBS-induced colitis exhibited a significant increase in TNF-α and IL-1β levels; 17 , 31 however, hemin treatment significantly decreased the level of these cytokines in a dose-dependent manner. Furthermore, hemin-treated mice also revealed a significant increase in the IL-10 concentration in a dose-dependent manner as expected, confirming the results obtained with TNF-α and IL-1β measurements.…”

Section: Discussionmentioning

confidence: 96%

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Hemin reduces inflammation associated with TNBS-induced colitis

Mateus¹,

Rocha²,

Mota-Filipe³

et al. 2018

CEG

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PurposeHemin is a heme-oxygenase inducer, which can confer anti-inflammatory, cytoprotective, and antiapoptotic effects. These properties are beneficial therapeutical effects to inflammatory bowel disease (IBD). IBD is a worldwide health problem characterized by chronic inflammation of intestinal epithelium, which promotes intestinal and extraintestinal symptomatology. Current treatment only induces and maintains the patient in remission and results in many side effects. The research of other pharmacologic approaches is crucial to the treatment of IBD. The aim of this study is to evaluate the effect of hemin in the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model.Materials and methodsMale CD-1 mice with TNBS-induced colitis were treated with a daily dose of hemin 5 mg/kg body weight/day and 10 mg/kg body weight/day intraperitoneal, during 4 days. The evaluated parameters were fecal hemoglobin, alkaline phosphatase (ALP), myeloperoxidase, tumor necrosis factor-α, interleukin (IL)-1β, IL-10, histopathologic analysis, urea, creatinine, and alanine aminotransferase.ResultsThe hemin-treated mice presented a decrease in fecal hemoglobin, ALP, and proinflammatory cytokine concentrations compared to the TNBS group. Histopathology analysis confirmed the decrease in lesion extension produced by hemin.ConclusionThese findings suggest that hemin treatment reduces hemorrhagic focus, intestinal damage, tissue inflammation, and lesion extension associated with experimental colitis.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 96%

See 2 more Smart Citations

Hemin reduces inflammation associated with TNBS-induced colitis

Mateus¹,

Rocha²,

Mota-Filipe³

et al. 2018

CEG

Self Cite

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“…Taken together, these findings support EPO's potential to activate anti-apoptotic signaling in dopaminergic neurons in vivo, which if true, would support an anti-apoptotic role of EPO in the nigrostriatal system and a possible mechanism of its protective activity. One possibility in this regard is that EPO may be exerting anti-apoptotic effects through the Bcl-2 family proteins via multiple Luo et al, 2016;Mateus et al, 2017;Nakamura et al, 2015;Villa et al, 2003). Reductions in TNF-α and IL-6, along with reduced astrocyte activation and microglial recruitment have also been reported in a rat model of ischemia (Villa et al, 2003).…”

Section: Epo In Animal Models Of Diseasementioning

confidence: 99%

Erythropoietin as a Modulator of Pathology in a Toxicant Mouse Model of Parkinson’s Disease

Thompson¹

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Parkinson's disease (PD) is the second most common neurodegenerative disorder and has no known disease-modifying treatments. Due to the complexity of the disease pathology, effective treatments for PD will likely involve a combination of treatment factors. The current experiments sought to profile the pro-survival effects of the trophic cytokine, erythropoietin (EPO), in a 6-hydroxydopamine (6-OHDA) mouse model of PD. Methods: To this end, male C57Bl/6 mice were used in a series of four experiments investigating the potential antiapoptotic, anti-inflammatory and antioxidant effects of the trophic cytokine. EPO's ability to protect dopaminergic terminals in the striatum, cell bodies in the substantia nigra (SNc) and modulate 6-OHDA-induced motor deficits was characterized at different doses of 6-OHDA and EPO. Results: Our results did indeed demonstrate EPO's ability to exert pro-survival effects that were brain region-specific. While intra-nigral EPO was ineffective, intra-striatal EPO preserved striatal terminals and nigral soma in two different 6-OHDA lesion models. EPO further attenuated apomorphine-induced rotations at two doses of 6-OHDA. EPO demonstrated antiapoptotic signalling through phosphorylation of Akt and the Bcl-2 associated proteins and antiinflammatory activity through modulation of microglial morphology. Finally, EPO demonstrated antioxidant activity through elevated levels of striatal glutathione peroxidase, in addition to retrograde signalling that resulted in elevated levels of glutathione peroxidase in the SNc in response to EPO treatment. Conclusions: In short, EPO appears to modify antioxidant and antiapoptotic factors and act in a brain-region specific manner to mitigate neuronal loss. Taken together, the results of the current set of experiments indicate EPO's potential for use as an adjuvant therapy in the treatment of PD.

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