Hypothalamic digoxin and inflammatory bowel disease

The isoprenoid pathway produces three key metabolites _ endogenous digoxin, dolichol and ubiquinone. It was considered pertinent to assess the pathway in inflammatory bowel disease (ulcerative colitis and regional ileitis). Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade was also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. The following parameters were measured in patients with inflammatory bowel disease and in individuals with differing hemispheric dominance - 1. plasma HMG CoA reductase, digoxin, dolichol, ubiquinone and magnesium levels, 2. tryptophan/tyrosine catabolic patterns, 3. free radical metabolism, 4. glycoconjugate metabolism, and 5. membrane composition and RBC membrane Na+-K+ ATPase activity. Statistical analysis was done by 'ANOVA'. In patients with inflammatory bowel disease there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in the cholesterol: phospholipid ratio and a reduction in the glycoconjugate level of RBC membrane in this group of patients. The same biochemical patterns were obtained in those with right hemispheric dominance. Inflammatory bowel disease is associated with an unregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to immune activation, defective glycoprotein bowel antigen presentation and autoimmunity, and a schizophreniform psychosis, important in its pathogenesis. Inflammatory bowel disease occurs in right hemispheric dominant individuals.

Keywords
Inflammatory bowel disease, Digoxin, Dolichol, Ubiquinone, Hemispheric dominance