A new technique for continuous measurement and recording of gastric potential difference in the rat: evaluation of NSAID-induced gastric mucosal damage.
Disruption of the gastric mucosal barrier by the so-called "barrier breakers" such as ethanol, aspirin, and bile is associated with an increase in gastric potential difference (GPD), that is, a decrease in its negativity. Because a good correlation between the degree of histological damage and changes in GPD has been observed, this parameter has been used increasingly as an index of mucosal integrity. However, the current methodology for measuring GPD is laborious due to the preparation and checking of KCl-agarose bridges prior to each experiment, and calculations--usually handmade--are time-consuming and inaccurate. In this paper, a new method allowing simultaneous measurement and recording of GPD in the rat is described. The method allows a simultaneous recording of intragastric pH and an automatic data analysis. The new technique has been validated by studying mucosal damage induced by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) (namely indomethacin and droxicam) as well as the mucosal protective activity of an antacid and sucralfate. The similarity between the results obtained in this rat model and those derived from human experiments clearly show that the developed methodology yields results that are predictive for human pharmacology.
Scarpignato
C
C
Institute of Pharmacology, School of Medicine and Dentistry, University of Parma, Italy.
Corradi
C
C
Gandolfi
M A
MA
Galmiche
J P
JP
D000704:Analysis of Variance; D000818:Animals; D000863:Antacids / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin / Q000633:toxicity; D004566:Electrodes; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D011725:Pyridines / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013392:Sucralfate / Q000494:pharmacology*
D000863:Antacids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D011725:Pyridines; D013392:Sucralfate; C049073:droxicam; D001241:Aspirin; D007213:Indomethacin