Intestinal ischemic preconditioning: less xanthine accumulation relates with less apoptosis.
Ischemic preconditioning has shown to reduce apoptosis in the intestinal mucosa during ischemia/reperfusion. This study evaluated if the decrease of apoptotic events found during preconditioning could be related with a reduction of the substrate (i.e., xanthine/hypoxanthine) available for xanthine oxidase (XO). Animals were randomly assigned to the following study groups: C, control; I/R, ischemia/reperfusion; P+I/R, ischemic preconditioning; P+I/R+H/X, ischemic preconditioning plus hypoxanthine/xanthine, and P+I/R+H/X+Allo, ischemic preconditioning plus hypoxanthine/xanthine plus allopurinol. Caspase-3 activity, DNA fragmentation and TUNEL staining increased in the I/R group compared to control. Ischemic preconditioning (P+I/R group) was able to reverse these apoptotic variables to a level similar to that of control rats. The addition of hypoxanthine/xanthine to rats subjected to ischemic preconditioning (P+I/R+H/X group) showed the highest apoptotic activity; however, further addition of allopurinol (P+I/R+H/X+Allo group) decreased significantly apoptotic activity and events. In conclusion, intestinal ischemic preconditioning is able to reduce apoptosis during the following sustained ischemia/reperfusion event because of a reduced accumulation of xanthine/hypoxanthine nucleotide.
Sola
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A
Department of Experimental Pathology, Instituto de Investigaciones Biomédicas, IIBB-CSIC, IDIBAPS, Barcelona, Spain.
Alfaro
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V
Hotter
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G
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007042:Hypoxanthines / Q000378:metabolism; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D007421:Intestine, Small / Q000502:physiology*; D019194:Ischemic Preconditioning; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology; D019820:Xanthine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007042:Hypoxanthines; D019820:Xanthine; D008315:Malondialdehyde; D000493:Allopurinol; D014969:Xanthine Oxidase; D020169:Caspases