Allopurinol inhibits lipid peroxidation in warm ischaemic and reperfused rabbit kidneys.
Rabbit kidneys were subjected to 120 min of warm ischaemia or to 120 min of warm ischaemia followed by 60 min reperfusion with blood in vivo before being removed, homogenised and incubated at 37 degrees C for 90 min. Lipid extracts were obtained and monitored for Schiff base (fluorescence emission 400-450 nm, excited at 360 nm), thiobarbituric acid (TBA)-reactive material (emission 553 nm, excited at 515 nm) and diene conjugates (absorbance at 237 nm). Samples removed before incubation were assayed for reduced glutathione (GSH) and oxidised glutathione (GSSG) to provide an index of glutathione redox activity (GSH:GSSG). Allopurinol injected systemically i.v. (a) 15 mins before kidneys were clamped, (b) 15 mins before they were reperfused or (c) as two injections (before clamping and before reperfusion) significantly inhibited these biochemical markers of lipid peroxidation. Administration before reperfusion had a markedly more pronounced effect than when allopurinol was given before warm ischaemia only. It is concluded that allopurinol is probably effective because of its ability to inhibit xanthine oxidase and consequently lipid peroxidation during reperfusion rather than by preventing loss of purine nucleotides from hypoxic cells during ischaemia.
Green
C J
CJ
Section of Surgical Research, MRC Clinical Research Centre, Harrow, U.K.
Healing
G
G
Simpkin
S
S
Gower
J
J
Fuller
B J
BJ
D000493:Allopurinol / Q000633:toxicity*; D000818:Animals; D001831:Body Temperature; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D006358:Hot Temperature; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D010084:Oxidation-Reduction; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism*
D005609:Free Radicals; D000493:Allopurinol; D005978:Glutathione