Phospholipase C-mediated intestinal mucosal damage is ameliorated by quinacrine.
Phospholipase C from Clostridium perfringens, when injected into a closed loop of the rat small intestine in vivo, caused an increase in the activity of intraluminal N-acetyl-beta-glucosaminidase and mucosal permeability to sodium fluorescein, indicating damage to the mucosa. Phospholipase C also caused an influx of granulocytes (neutrophils) into the mucosa, as shown by the myeloperoxidase activity--a granulocyte neutrophil marker, and increased localized lipid peroxidation. Pretreatment of animals with quinacrine, a known inhibitor of phospholipase A2, prevented the increases in the luminal N-acetyl-beta-glucosaminidase activity, mucosal permeability, malondialdehyde and myeloperoxidase activity after deposition of phospholipase C in the gut lumen. It is concluded that phospholipase C might impair the function of the mucosal barrier and increase the permeability of the gut to undesirable molecules and pathogens. Part of its action may be mediated via phospholipase A2 activation since pretreatment with quinacrine afforded protection.
Otamiri
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Clinical Research Center, University Hospital, Linköping, Sweden.
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D008054:Lipid Peroxides / Q000096:biosynthesis; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D008054:Lipid Peroxides; D009195:Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D011796:Quinacrine