Repair of mucosal damage induced by ethanol in the rat stomach. Effects of concentration, exposure period and prostaglandins.
We investigated the relationship between the severity of acute injury and the rapidity of mucosal repair in stomachs of anesthetized rats, and examined the influence of prostaglandins (PGs) on the process of restoration. Different degrees of mucosal damage were produced using ethanol and by varying the concentration (5-100%) and the exposure period (1-60 min). Exposure of the stomach for 10 min to ethanol induced hemorrhagic lesions and a reduction in the transmucosal potential difference (PD); its severity and its magnitude were increased in a concentration-related manner. After removal of ethanol, the reduced PD recovered quickly in the case of 5-25% ethanol, but it normalized slowly or did not show any recovery in the case of 50 or 100% ethanol, respectively. Histologically, ethanol at 5-25% produced various degrees of damage in the superficial epithelial cells, while the damage was deeper into the mucosa beyond the basal lamina after exposure to ethanol at 50% or greater. Similar phenomena were observed after exposure to 50% ethanol for various periods; the rapidity of PD recovery and mucosal restoration was faster when the exposure period was less than 2 min, and these parameters became slower as it was increased. Moreover, the PD recovery was significantly expedited or delayed, respectively, by 16,16-dimethyl PGE2 (30 micrograms/kg) or indomethacin (5 mg/kg), and the former counteracted the inhibitory effect of indomethacin. These results suggest that the process of mucosal regeneration may largely depend on the severity of damage initially formed, and probably involves factors sensitive to endogenous PGs.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Nishiwaki
H
H
Osano
H
H
Ebara
S
S
Okabe
S
S
D000279:Administration, Cutaneous; D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage / Q000627:therapeutic use*; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D013272:Stomach Diseases / Q000139:chemically induced / Q000188:drug therapy; D013997:Time Factors
D000431:Ethanol; D015232:Dinoprostone; D007213:Indomethacin