SIGNAL TRANSDUCTION PATHWAYS FOR CELL SURVIVAL OR APOPTOSIS BY TRI- AND PENTAVALENT ARSENIC IN RAT BRAIN

Abstract

Arsenate and arsenite affect the brain tissue in a dose independent manner and follow different pathways to exert their toxic effects. Arsenate present in the drinking water is highly toxic at 0.1ppm concentration and causes an array of metabolic disturbances like increased LPO, decreased GSH, increased NOS activity in rat brain. At higher doses also arsenate has damaging effects on biological systems but might follow different mechanism and coadministration of an antioxidant as per normal requirement of rat can control the lipid peroxidation and glutathione level to some extent, but cannot give significant protection against increased nitric oxide synthase activity which eventually causes nuclear changes at DNA or protein level and alter a number of physiological processes in the rat brain. Both arsenate and arsenite significantly affect specific signal transduction molecules in the glial cell population in the brain that are involved in mediating cellular transformation or apoptosis, including MAPKs, NF+kB, PI3K, Akt etc. High concentration of arsenic exposure may lead to apoptosis, whereas a low concentration of arsenic exposure is carcinogenic and may result in aberrant cell accumulation.