Effect of a new inhibitor of lipid peroxidation on kidney function after ischaemia-reperfusion. A study on rat and rabbit kidneys.
Lipid peroxidation of mitochondrial and cell membrane structures is the final step in the oxygen radical-induced damage observed at reperfusion of kidneys after ischaemia. We compared the ability of an indeno-indol compound (code name H290/51) with that of alpha-tocopherol to inhibit lipid peroxidation in reoxygenated isolated rat renal tissue in vitro measured as production of TBARS (thiobarbituric acid reactive substances). H290/51 was 100 times more efficient than alpha-tocopherol. Treatment of rats in vivo with H290/51 in a dosage giving a plasma concentration of 500 nmol L-1 inhibited TBARS production measured in vitro by 80%. Treatment of rabbits with H290/51 almost completely inhibited radical production at reperfusion after 60 min of ischaemia measured with spin trap technique using OXANOH (2-ethyl-3-hydroxy-2,4,4-trimethyloxazolidine) as a spin trap. Furthermore, such pretreatment significantly improved kidney function and survival of rabbits subjected to 60 min of ischaemia to the left kidney and contralateral nephrectomy. These studies stress the importance of inhibiting lipid peroxidation to prevent the ischaemia-reperfusion damage and furthermore suggest a role for treatment with antioxidants like H290/51 in clinical practice, e.g. at reconstructive renal surgery and transplantation.
Sørensen
V
V
Department of Urology, Sablgrenska sjukhuset, University of Göteborg, Sweden.
Nilsson
U
U
Pettersson
S
S
Scherstén
T
T
Sjöqvist
P O
PO
Svensson
L
L
Jonsson
O
O
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D004234:Diuretics, Osmotic / Q000494:pharmacology; D005260:Female; D005609:Free Radicals; D066298:In Vitro Techniques; D007211:Indoles / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects*; D008353:Mannitol / Q000494:pharmacology; D009392:Nephrectomy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D004234:Diuretics, Osmotic; D005609:Free Radicals; C088233:H290-51; D007211:Indoles; D017392:Thiobarbituric Acid Reactive Substances; D008353:Mannitol