title: Possible association between cell membrane band 3 impairment function and renal tubular acidosis (liver diseases, malignancies and adverse drug reactions).
abstract: Renal tubular acidosis (RTA) more frequently develops in case of chronic diseases of inflammatory-immunological origin. RTA is well known to be associated with chronic liver disease (CLD), with nephrolithiasis, common cases of RTA occur among cancer patients. Abnormalities in the expression or function of band 3 in cell membrane may play a role in the pathogenesis of RTA. Cl-/HCO3- anion exchanger (AE2) is an isoform of band 3 protein, which is expressed in cell membranes of organs such as liver cells and kidney endothelium. There are reports on downregulated AE2 immunoreactivity in the liver of patients with chronic liver diseases and in the kidney tubular tissue of patients with RTA. The proteolytic damage of cell membrane band 3 in tissues could be related to inflammatory-immunological processes. Another important factor able to disturb the band 3 function is medicinal products used in the treatment of certain pathologies. The active substance of a drug itself may have a direct effect on this protein or trigger a pathological process. In such cases ADR can take place and may be evaluated as such. Acid-base disturbances, notably metabolic acidosis, are a serious complication of drug treatment. Reduced AE2 expression or its changed activity (congenital or acquired) could be related with alterations of intracellular pH. This could lead to antigenic changes and autoimmunity. The derangement of band 3 function in organ cell membrane could act as a factor which creates an "acidotic environment" for organ cells. Such circumstances could be the reason for unsuccessful treatment or determine resistance of tumor treatment. The understanding of the mechanisms of RTA development, early diagnostics, and knowledge of the drugs that can cause RTA, are of particular practical significance.
authors.affiliation: Institute of Oncology, Vilnius University, Santariskiu 1, 2000 Vilnius, Lithuania. donatasstakisaitis@vvkt.lt
authors.forename: Donatas
authors.initials: D
authors.lastname: Stakisaitis
authors.forename: Janina
authors.initials: J
authors.lastname: Didziapetriene
authors.forename: Romaldas
authors.initials: R
authors.lastname: Maciulaitis
authors.forename: Marina
authors.initials: M
authors.lastname: Tschaika
mesh_terms: D000137:Acid-Base Imbalance / Q000139:chemically induced; D000141:Acidosis, Renal Tubular / Q000139:chemically induced* / Q000175:diagnosis / Q000209:etiology*; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D000936:Antigen-Antibody Complex / Q000276:immunology; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015551:Autoimmunity; D002908:Chronic Disease; D004195:Disease Models, Animal; D018432:Drug Resistance, Multiple; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006505:Hepatitis / Q000150:complications; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007049:Iatrogenic Disease; D018836:Inflammation Mediators / Q000276:immunology; D007669:Kidney Calculi / Q000150:complications; D008107:Liver Diseases / Q000150:complications*; D008297:Male; D051379:Mice; D009154:Mutation; D009369:Neoplasms / Q000150:complications*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D000936:Antigen-Antibody Complex; D000970:Antineoplastic Agents; D018836:Inflammation Mediators