The effect of the cholinergic anti-inflammatory pathway on experimental colitis.
ABSTRACT Inflammatory bowel diseases (IBD) are characterized by proinflammatory cytokines, tissue damage and loss of neuron in inflamed mucosa, which implies the cholinergic anti-inflammatory pathway may be destroyed during the process of inflammatory response. In the study, we identified the effect of cholinergic agonist as anabaseine (AN) and nicotinic receptor antagonist as chlorisondamine diiodide (CHD) on trinitrobenzene sulfonic acid (TNBS)-induced colitis, to investigate the potential therapeutic effect of the cholinergic anti-inflammatory pathway on IBD. Experimental colitis was induced by TNBS at day 1, 10 mug AN or 1.5 mug CHD was injected i.p. to mouse right after the induction of colitis, and repeated on interval day till the mice were sacrificed at day 8. Colonic inflammation was examined by histological analysis, myeloperoxidase (MPO) activity, and the production of tumour necrosis factor (TNF)-alpha in tissue. Lamina propria mononuclear cells (LPMC) were isolated, and NF-kappaB activation was detected by western blot. The mice with colitis treated by AN showed less tissue damage, less MPO activity, less TNF-alpha production in colon, and inhibited NF-kappaB activation in LPMC, compared with those mice with colitis untreated, whereas the mice with colitis treated by CHD showed the worst tissue damage, the highest MPO activity, the highest TNF-alpha level, and enlarged NF-kappaB activation in LPMC. Agonist of the cholinergic anti-inflammatory pathway inhibits colonic inflammatory response by downregulating the production of TNF-alpha, and inhibiting NF-kappaB activation, which suggests that modulating the cholinergic anti-inflammatory pathway may be a new potential management for IBD.
Article: Multiple approaches to analyse the data for rat brain acetylcholinesterase inhibition by cyclophosphamide.[show abstract] [hide abstract]
ABSTRACT: Acetylcholinesterase (AChE) is an externally oriented membrane-bound enzyme and its main physiological role is termination of chemical transmission at cholinergic synapses and secretory organs by rapid hydrolysis of the neurotransmitter acetylcholine (ACh). Nevertheless, it is well known that cyclophosphamide (CP; nitrogen mustard derivative) is an eminent anticancer drug. The present work addresses multiple approaches to analyze an identical data for rat brain AChE inhibition by CP. These different angels of analysis based on two classical (Lineweaver-Burk as well as Dixon) plots, their secondary replots, a new graphical approach and general built-in equations of GOSA. Thus various kinetic constants (K(I), K(s,) K(m), k(sl), V(mao), K(i), k(sli), S(lo), K(maxi), S(K0.5), k(cat) and k(sp)) were estimated and mode of inhibition discussed in the current study.Neurochemical Research 10/2010; 35(10):1501-9. · 2.24 Impact Factor