The effect of smoking on intestinal inflammation: What can be learned from animal models?

Mechanisms of oxidative damage. Panel A shows the generation of reactive oxygen metabolites (ROMs). These metabolites can be formed by an enzymatic reaction out of oxygen. However, several ROMS are also present in cigarette smoke (bold). Panel B shows the production of reactive nitrogen metabolites. These are normally formed as a side product of the transformation of l-arginine into citrulline by NOS. But as is the case with ROMs, several nitrogen reactive metabolites are components of cigarette smoke. The formation of highly reactive metabolites including superoxide anion, the hydroxyl radical and NO₃⁻ result in damage to DNA, lipids and proteins causing tissue damage. The green arrows indicate protective anti-oxidant pathways, which decrease oxidative stress. GSH: gluthatione, GSSG: oxidized gluthatione, GPx: gluthatione peroxidase, iNOS: inducible nitric oxide synthase, SOD: superoxide dismutase, XO: xanthine oxidase.

Divergent effect of smoking on the small bowel and the colon. Evidence from animal models shows that smoke exposure has a detrimental effect on the small bowel immunology, predisposing it towards increased vulnerability to inflammatory stimuli. For the colon, more ambiguous effects are described in the different models. Other factors, such as the intestinal commensal flora, viral or bacterial pathogens, and genetic predisposition manipulating the metabolism of various smoke constituents will determine whether beneficial or rather unfavorable effects will take over.