An in vitro assessment of the effect of cytotoxic drugs upon the intestinal absorption of nutrients in rats

Effect of Vitamin A against Methotrexate-Induced Damage to the Small Intestine in Rats

“…The antimitotic effect of MTX is known to give rise to the malabsorption syndrome [2][3][4] that decreases the surface area for absorption caused by histological alterations such as shortened microvilli, resulting in less absorption of nutrients [5]. In addition, MTX depresses absorption of certain drugs from the small intestine [5], metabolic activity and active transport capacity of the intestinal mucosa [6]. It also decreases the brush border membrane protein and lipid contents of the small intestine [5,7] and inhibits the enzyme dihydrofolate reductase, which is required for DNA synthesis and cell division [8,9].…”

Radiation and the Small Intestine

“…In radiobiology, explanations of the oxy gen effect have previously emphasized the mechanistic involvement of superoxide or its conjugate acid, the hydroperoxyl radical [17], Contrary opinion discounted these ex planations and alternative accounts of the oxygen effect(s) have since been advanced [1], Nevertheless, the specificity with which superoxide dismutase (SOD) catalyzes the destruction of superoxide anions, together with the recent demonstration of the radioprotective effect of SOD on membranes, en zymes, bacteriophage, bacteria, mycoplasma and mammalian cells [62,66,74,75] sug gests that a superoxide-mediated component of the oxygen effect exists which is discerni ble and to some extent inhibitable.…”

Is folate absorption impaired by high dose methotrexate?

“…( Delmonte & Jukes, 1962) The functional effects of toxicity could be responsible for such MTX-induced methotrexate enterotoxicity have been widely malabsorption. A local toxic effect on villos cells studied in the experimental animal (Shaw et al, might be a consequence of the high biliary 1979, Capel et al, 1979, Taminiau et al, 1980 but concentrations of MTX after high dose therapy absorption has been measured when there was (Halsted, 1972). MTX also lowers intestinal mucosal severe villos atrophy and dysfunction was pH and impairs folate uptake (Lei et al, 1977) and therefore to be expected.…”