Microtubules are structural components of the cytoskeleton that lengthen and shrink for important cell functions. Colchicine binds to β- tubulin and forms tubulin-colchicine complexes., These complexes interfere with microtubule formation microtubules. Low doses of colchicine can inhibit the formation of microtubules, while high doses depolymerize or break down a polymer to a monomer. Therefore, any process involving cytoskeleton change, including mitosis and motility of white blood cells, are highly impacted.Microtubule disruption decrease neutrophil adhesion, an important step for inflammation. Neutrophils are recruited to the target location of inflammation via signals from the endothelium where they adhere and play a role in the inflammatory response. Colchicine diminishes neutrophil adhesion by decreasing expression of selectins, a family of cell adhesion molecules. In addition, colchicine prevents the movement and secretion of intercellular granules, substances, proinflammatory enzymes from neutrophils, thus making a significant impact on inflammatory processes within the body. The high concentration of colchicine in neutrophils, sixteen times greater compared the plasma levels, can account for the positive therapeutic effects.Many mediators are altered to assist neutrophils during inflammation, including the monokine tumor necrosis factor-alpha (TNFα). Cytokines help stimulate the acute phase reaction in response to inflammation. Colchicine inhibits macrophage production of TNFα, leading to the interference between TNFα and neutrophil interaction. There are many more effects of colchicine that are currently under research, and some aspects of this metabolite are not fully understood.There was great hope that Colchicine could be a primary preventive measure in treating Post-Pericardiotomy Syndrome due to its anti-inflammatory effects.
These epigenetic alterations are due to H. pylori-induced methylation of CpG sites in promoters of genes and H. pylori-induced altered expression of multiple microRNAs.As reviewed by Santos and Ribeiro H. pylori infection is associated with epigenetically reduced efficiency of the DNA repair machinery, which favors the accumulation of mutations and genomic instability as well as gastric carcinogenesis. In particular, Raza et al. showed that expression of two DNA repair proteins, ERCC1 and PMS2, was severely reduced once H. pylori infection had progressed to cause dyspepsia. Dyspepsia occurs in about 20% of infected individuals. In addition, as reviewed by Raza et al., human gastric infection with H. pylori causes epigenetically reduced protein expression of DNA repair proteins MLH1, MGMT and MRE11. Reduced DNA repair in the presence of increased DNA damage increases carcinogenic mutations and is likely a significant cause of H. pylori carcinogenesis. Survival of Helicobacter pylori
The pathogenesis of H. pylori depends on its ability to survive in the harsh gastric environment characterized by acidity, peristalsis, and attack by phagocytes accompanied by release of reactive oxygen species. In particular, H. pylori elicits an oxidative stress response during host colonization. This oxidative stress response induces potentially lethal and mutagenic oxidative DNA adducts in the H. pylori genome.Vulnerability to oxidative stress and oxidative DNA damage occurs commonly in many studied bacterial pathogens, including Neisseria gonorrhoeae, Hemophilus influenzae, Streptococcus pneumoniae, S. mutans, and H. pylori. For each of these pathogens, surviving the DNA damage induced by oxidative stress appears supported by transformation-mediated recombinational repair.