An In Vitro Model of Gastric Inflammation and Treatment with Cobalamin

Abstract

Pernicious anaemia (PA) is an autoimmune condition where antibodies target intrinsic factor and parietal cells, reducing the patient's ability to absorb cobalamin promoting atrophic gastritis. Treatment guidelines are based on excretion data of hydroxocobalamin from healthy individuals obtained 50 years ago. This manuscript describes the use of phorbol 12-myristate 13-acetate (PMA) to stimulate low grade inflammation in an epithelial colorectal cell line to assess the efficacy of methylcobalamin and hydroxocobalamin. Nitric oxide increased significantly in cells exposed to higher doses of PMA (100 ng/ml, 150 ng/ml, and 200 ng/ml) accompanied by a loss of the characteristic cobblestone morphology with no negative effect on cell activity or viability. A significant reduction in nitric oxide production was associated with the addition of 200 pg/ml hydroxocobalamin, alongside a return to the characteristic cobblestone morphology. This study highlights the use of PMA to promote low grade inflammation in human cell lines to model gastric inflammation associated with autoimmunity; furthermore it raises questions regarding the concentration of cobalamin administered clinically to restore cell functionality, feasibly allowing the patient to receive reduced quantity of the vitamin more regularly, providing the patient with levels which are akin to dietary intake.

Cobalt(II) Diphenylazodioxide Complexes Induce Apoptosis in SK-HEP-1 Cells

“…2 Other transition metals have been explored in cancer therapy, such as ruthenium 2a,2b,3 osmium, 2c rhodium, 4,5a and iridium, 5 but nonplatinum anticancer drugs in clinical use remain predominantly organic. In particular, despite the high natural abundance of cobalt 6 and the extensive synthetic chemistry of its complexes, there are, to the best of our knowledge, so far no cobalt compounds in widespread clinical use other than vitamin B 12 (cobalamin), 7 though the cobalt(III) imine complex CTC-96 (Doxovir) has been explored as a treatment for herpes simplex virus, 8 reaching phase II clinical trials. 8b…”

Pernicious Anemia and Vitiligo in an HIV Patient: An Unfamiliar Case Presentation

“…Our patient responded well to parenteral vitamin B12 and steroid therapy. Vitamin B12, given as hydroxocobalamin, has also been shown to reduce the gastric inflammatory process as well as retard the development of immune dysfunction associated with HIV/AIDS [14,15]. On the other hand, short course steroid therapy was given as adjunct treatment, as it has been shown that corticosteroids improve vitamin B12 absorption by reducing gastric inflammation [16].…”