alpha-chaconine and Inflammatory-Bowel-Diseases

Inflammatory bowel disease (IBD) may be initiated following disruption of the intestinal epithelial barrier. This disruption, in turn, permits luminal antigens unfettered access to the mucosal immune system and leads to an uncontrolled inflammatory response. Glycoalkaloids, which are found in potatoes, disrupt cholesterol-containing membranes such as those of the intestinal epithelium. Glycoalkaloid ingestion through potatoes may play a role in the initiation and/or perpetuation of IBD.. To determine if commercial and high glycoalkaloids containing fried potato skins aggravate intestinal inflammation using two different animal models of IBD.. Fried potato skins from commercial potatoes containing low/medium glycoalkaloid levels and high glycoalkaloids potatoes were fed for 20 days to interleukin 10 gene-deficient mice and dextran sodium sulfate-induced colitic mice. Intestinal permeability, mucosal cytokine and myeloperoxidase levels and body weight were determined to assess intestinal injury.. Deep frying potato skins markedly increased glycoalkaloid content. Interleukin 10 gene-deficient mice fed fried commercial potato skins with medium glycoalkaloid content exhibited significantly elevated levels of ileal IFN-γ relative to controls. Mice in the dextran sodium sulfate colitis model that were fed the same strain of potatoes demonstrated significantly elevated levels of pro-inflammatory cytokines IFN-γ, TNF-α, and IL-17 in the colon in addition to an enhanced colonic permeability. Inflammatory response was intensified when the mice were fed potatoes with higher glycoalkaloid contents.. Our results demonstrate that consumption of potato skins containing glycoalkaloids can significantly aggravate intestinal inflammation in predisposed individuals.

Topics: Animals; Colitis, Ulcerative; Cooking; Crohn Disease; Cytokines; Dextran Sulfate; Disease Models, Animal; Genetic Predisposition to Disease; Inflammatory Bowel Diseases; Intestinal Mucosa; Mice; Peroxidase; Solanaceous Alkaloids; Solanine; Solanum tuberosum

Disruption of epithelial barrier integrity is important in the initiation and cause of inflammatory bowel disease (IBD). Glycoalkaloids, solanine (S), and chaconine (C) are naturally present in potatoes, can permeabilize cholesterol-containing membranes, and lead to disruption of epithelial barrier integrity. Frying potatoes concentrates glycoalkaloids. Interestingly, the prevalence of IBD is highest in countries where fried potatoes consumption is highest.. To further understand the role of potato glycoalkaloids on intestinal barrier integrity, we examined the effect of varying concentrations of solanine and chaconine on intestinal permeability and function.. Solanine (0-50 microM), chaconine (0-20 microM), or a 1:1 mixture (0-20 microM) were exposed to T84 cultured epithelial monolayers for varying periods of time to determine concentration response effect on epithelial permeability. Next, a 1:1 mixture (5 microM) of solanine-to-chaconine (C:S) was exposed to sheets of normal murine small intestine, mounted in Ussing chambers, from control and interleukin-10 gene-deficient mice to determine whether glycoalkaloids affected intestine from mice with a genetic predisposition for IBD greater than controls. Finally, the effects of glycoalkaloids on colonic histologic injury were examined in mice orally fed amounts of glycoalkaloids that would normally be consumed in a human diet.. Glycoalkaloids embedded and permeabilized the T84 monolayer epithelial membrane bilayer in a concentration-dependent fashion, with C:S > C > S. In vitro Ussing chamber experiments also illustrated a concentration-dependent disruption of intestinal barrier integrity in animals with a genetic predisposition to develop IBD, but not in control animals. Similarly, in vivo oral feeding experiments demonstrated that C:S ingestion, at physiologic concentrations, aggravated histologic colonic injury in mice genetically predisposed to developing IBD.. Concentrations of glycoalkaloids normally available while eating potatoes can adversely affect the mammalian intestine and can aggravate IBD.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; In Vitro Techniques; Inflammatory Bowel Diseases; Intestinal Mucosa; Mice; Permeability; Solanaceous Alkaloids; Solanine; Solanum tuberosum; Time Factors