Functional and morphological structure changes in the gut barrier during cholinesterase inhibitor intoxication and therapeutic effect of benthiactzine in rats

Abstract

To investigate the functional and morphological structure changes in the gut barrier of rats induced by cholinesterase inhibitor VX poisoning, and the therapeutic effect of benthiactzine. Forty male Wistar rats were randomly divided into five groups: normal saline control group, VX poisoning (model) group, benthiactzine 1, 3, 9 mg/kg treatment groups, with 8 rats in each group. In the benthiactzine treatment groups, different dosages of the drug were respectively given (intraperitoneal injection) 5 minutes after VX poisoning (13 microg/kg subcutaneous injection). The plasma concentration of D-lactate and the diamine oxidase (DAO) activity, which reflected the gut barrier function, were measured at 3 hours after VX poisoning. At the same time point, the specimens from jejunum and ileum were harvested. The morphological changes in the intestinal mucosa were determined with light microscope and electron microscope. After VX poisoning, the plasma D-lactate concentration and the DAO activity in model group were significantly increased compared with those of control group [D-lactate concentration in model group was (87.752 + or - 22.906) mg/L which was higher than that of control group (29.072 + or - 6.546) mg/L; DAO activity in model group was (6.72 + or - 0.93) U/L which was higher than that of control group (2.99 + or - 0.43) U/L, both P<0.01]. These values could be decreased dose-dependently after benthiactzine 1, 3, 9 mg/kg administration after the VX poisoning. Furthermore, the increase in D-lactate (45.290 + or - 11.141) mg/L and DAO activity (3.17 + or - 0.68) U/L could be totally reversed by 9 mg/kg of benthiactzine (both P<0.01). In model group, the intestinal mucosal epithelial injury was obvious at 3 hours after VX poisoning as shown under light microscope, including diminution of the mucosal thickness and the height of villi in jejunum and ileum, interstitial edema, angiotelectasis. Also electronic microscopic examination revealed damaged organelles and cell tight junction of mucosal epithelium. These pathological changes in intestine could be inhibited by benthiactzine in dose-dependent manner. The gut barrier function in rats was seriously damaged by the cholinesterase inhibitor agents poisoning, as a result of injury to intestinal mucosa and increase of intestinal permeability. Benthiactzine exerts protection against functional and morphological structure damages of the gut barrier during intoxication.