Abstract
Aim: Monochloramine (NH2Cl) is a thiol‐directed oxidant produced in inflamed, H. pylori‐infested gastric mucosa. We tested the hypothesis that NH2Cl‐induced death of isolated gastric glands can be reversed by thiol reducing agents such as dithiothreitol (DTT) or Lipoic Acid (LA) but not oxidant scavengers such as Vitamin C (VitC).Methods: Isolated rabbit gastric glands were incubated with Ringers solutions containing NH2Cl for 1 hour, then Ringers solution for 2 hours. Cell viability was monitored, using calcein‐AM uptake and conversion to fluorescent calcein, during exposure to NH2Cl. In some studies, DTT, LA or VitC were present throughout the entire 3 hr experiment; in others, they were present only following the 1 hr exposure to NH2Cl.Results: Exposure to NH2Cl resulted in significant (p<0.05) and dose‐dependent decreases in cell viability. Both DTT and Vitamin C were significantly protective when co‐administered with NH2Cl. Only DTT provided partial reversal of injury when given after NH2Cl. No protection was observed in response to LA, given concurrently or after exposure to NH2Cl.Conclusion: Some, but not all, thiol reducing agents protect gastric glands from NH2Cl‐induced injury by concurrent administration and can arrest and reverse injury after exposure to the oxidant. Generic oxidant scavengers can prevent, but do not reverse, injury. Funding: APS Summer Research Fellowship, NIH R01DK069929‐03
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