INTESTINAL MOTILITY DISORDER INDUCED BY FREE RADICALS: A NEW MODEL MIMICKING OXIDATIVE STRESS IN GUT

Literature data suggest that the inflamed intestine may be subjected to a considerable oxidative stress. Therefore, the aim of the present study was to simulate the oxidative stress in the gastrointestinal tract and to explore its effect on intestinal motility. This was attained by treating isolated segments from the rabbit jejunum and from the guinea pig ileum with 2,2′-Azobis (2-amidinopropane) dihydrochloride (ABAP), which generates peroxyl radicals by thermal decomposition. Treatment of intestinal segments with ABAP reduced the muscarinic cholinergic response to acetylcholine in both preparations and induced a dose-dependent inhibition of the spontaneous contractions in the jejunum, also in the presence of tetrodotoxin. ABAP was found to inhibit the contractile response induced by BaCl2 in guinea pig ileum preparations. This effect was not dose-dependent and it was reversed by Bay-K 8644, which activates voltage operated L-type calcium channels. The rapid and reversible effects of ABAP suggest that it might directly affect L-type calcium channels before lipoperoxidation induction. In conclusion, the results of the present study show that ABAP could be a useful tool to simulate early contractility dysfunctions mediated by oxidative stress. [Copyright &y& Elsevier]