Dibromoacetonitrile - induced gastric toxicity in rats: role of xanthine oxidase

ABSTRACT

Dibromoacetonitrile [DBAN] is a disinfectant by-product of drinking water chlorination. Epidemiological studies indicate that exposure to haloacetonitriles via drinking water might present a potential hazard to human health. The objective of the present study was to investigate the role of xanthine oxidase [XO] I DBAN-induced toxicity in rat gastric tissues. A single oral dose of DBAN [50 mg/kg] caused a significant enhancement in XO activity. Maximum XO activity was observed at 2 h after DBAN treatment and amounted to 428% of the control enzymatic activity. DBAN also caused a significant depletion of reduced glutathione [GSH] levels and enhanced superoxide anion [O[2]] production in gastric tissues. This was accompanied by increased lipid peroxidation [determined as malondialdehyde; MDA formation] all over the time-course experiment. In addition, a dose-response experiment was established in which DBAN was given at 3 dose levels [25, 50 or 100 mg/kg]. The highest dose of DBAN [100 mg/kg] accelerated the conversion of xanthine dehydrogenase [XD] to XO; as the XO was elevated up to 35.53% compared to 7.42% of the total XD/SO activity in control rats. DBAN caused a significant depletion of gastric GSH in a dose-related manner. A strong correlation existed between the levels of GAS and the percentage enhancement in XO activity [r[2] = -0.95]. O[2] production and MDA formation were significantly elevated in a dose-related manner. To further substantiate the role of XO and GSH depletion in DBAN-induced toxiciy, the XO inhibitor; allpurinol [50 mg/kg, p.o.] or GSH-depletor, diethylmaleate [DEM, 400 mg/kg, p.o.] were given before DBAN [50 mg/kg] administration, Allopurinol significantly protected against DBAN-induced rise in XO activity depletion of GSH and elevated reduction of O[2]. Pretreatment with DEM significantly aggravated the DBAN-induced GSH depletion and rise in XO activity from 28.21% to 39.56% of the total XO/XD activity. Furthermore, DEM significantly enhanced O[2] and MDA production. The present data indicate that enhancement of XO activity is implicated in DBAN-induced gastric damage in rats