Phospholipase A2 inhibition prevents mucosal damage associated with small intestinal ischaemia in rats.
The influence of various inflammatory inhibitors on the damaging effects of ischaemia in the small intestinal mucosa has been investigated. A rat experimental model was used, in which a ligated loop of the distal ileum was subjected to ischaemia and revascularisation and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. The mucosal content of malondialdehyde - a lipid peroxidation product - and its activity of myeloperoxidase - a neutrophil granulocyte marker was also determined. In the absence of inhibitor, ischaemia and revascularisation caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa and increased myeloperoxidase activity in the mucosa. All these effects were inhibited by the phospholipase A2 inhibitors, quinacrine and nordihydroguaiaretic acid (NDGA), while the lipoxygenase inhibitor, BW755C, had no influence and the cyclooxygenase inhibitor, indomethacin, potentiated the increases in mucosal permeability and N-acetyl-glucosaminidase release. BN 52021, a specific platelet activating factor antagonist, did not influence the myeloperoxidase activity, but it decreased the formation of malondialdehyde and the increases in mucosal permeability and N-acetyl-beta-glucosaminidase release, although not to the same extent as quinacrine and NDGA. These findings indicate that phospholipase A2 inhibition prevents mucosal damage associated with small intestinal ischaemia and suggest that at least part of the ischaemic damage is mediated by products of phospholipase A2 activity that are not arachidonic acid metabolites.
Otamiri
T
T
Clinical Research Centre, Linköping, Sweden.
Lindahl
M
M
Tagesson
C
C
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000098:blood supply*; D007421:Intestine, Small / Q000098:blood supply* / Q000378:metabolism; D007511:Ischemia / Q000201:enzymology*; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010740:Phospholipases / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology*; D054467:Phospholipases A2; D051381:Rats
D008315:Malondialdehyde; D009195:Peroxidase; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D000118:Acetylglucosaminidase