Protective role of heme oxygenase-1 on trinitrobenzene sulfonic acid-induced colitis in rats

Abstract

Preliminary studies showed that the inducible form of heme oxygenase (HO-1) was induced and played a protective role in the process of inflammation. The present study investigated the possible role of HO-1 in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. We measured HO-1 activity in TNBS-induced colitis in rats and analyzed the severity of colitis along with altered HO activity by assessing lesion area and myeloperoxidase activity. HO-1 mRNA and protein expressions were determined at different time points after TNBS induction. Free radical production and inducible nitric oxide synthase (iNOS), which participate in oxidative injury, were also assayed. HO activity and HO-1 gene expression increased markedly after TNBS induction. Administration with tin mesoporphyrin (SnMP), a HO inhibitor, potentiated the colonic damage along with a reduction in HO-1 activity. Furthermore, the reduction of HO-1 expression by SnMP also enhanced reactive oxygen species and iNOS expression, both of which were dramatically increased after the TNBS enema. L-Arginine pretreatment further aggravated the injurious action of SnMP. Our results indicate that HO-1 plays a protective role in the colonic damage induced by the TNBS enema, and the preventive effects probably result from decreased free radical production and inhibition of iNOS expression in colonic tissues.

High-dose green tea polyphenols induce nephrotoxicity in dextran sulfate sodium-induced colitis mice by down-regulation of antioxidant enzymes and heat-shock protein expressions

“…Excess generation of ROS caused by the gut microenvironment breaks intestinal antioxidant systems in mice with DSS-induced colitis, thereby contributing to intestinal oxidative injury and initiating pro-inflammatory signaling (Tanaka et al 2007). In addition, several studies have demonstrated that inhibition of an antioxidant enzyme, heme oxygenase-1 (HO-1), leads to aggravation of DSSinduced colitis (Paul et al 2005;Wang et al 2001).…”

Protective Roles of CX3CR1-Mediated Signals in Toxin A-Induced Enteritis through the Induction of Heme Oxygenase-1 Expression

“…HO-1, also known as heat shock protein 32, is a rate-limiting enzyme in the degradation of heme into biliverdin, carbon monoxide, and iron (50,51) and can attenuate tissue injury caused by various inflammatory stimuli (33)(34)(35)(52)(53)(54)(55)(56). We observed that an HO-1 inhibitor, SnPP, aggravated toxin A-induced enteritis, as evidenced by an increased fluid accumulation in WT mice.…”

TI-I-174, a Synthetic Chalcone Derivative, Suppresses Nitric Oxide Production in Murine Macrophages via Heme Oxygen-ase-1 Induction and Inhibition of AP-1

“…Previous studies have shown that HO-1 induction plays an important role in a number of cytoprotection responses, including anti-oxidative and anti-apoptotic effects (Motterlini et al, 2000) and a growing body of evidence has indicated that HO-1 induction acts an adaptive defense mech-www.biomolther.org anism to protect cells from various pathophysiological conditions (Maines, 1997). In addition, recent studies have also revealed that HO-1 induction modulates inflammatory process via suppressing the production of pro-inflammatory mediators, such as COX-2, TNF-α and iNOS (Wang et al, 2001). Furthermore, deficiency of HO-1 in mice exhibited a severe inflammation (True et al, 2007), while HO-1 over-expression prevented inflammatory responses in various experimental conditions (Otterbein et al, 2003;Onyiah et al, 2013).…”

“…, 1997). In addition, recent studies have also revealed that HO-1 induction modulates inflammatory process via suppressing the production of pro-inflammatory mediators, such as COX-2, TNF-α and iNOS (Wang et al, 2001). Furthermore, deficiency of HO-1 in mice exhibited a severe inflammation (True et al, 2007), while HO-1 over-expression prevented inflammatory responses in various experimental conditions (Otterbein et al, 2003;Onyiah et al, 2013).…”