Renoprotective effect of trolox against ischaemia-reperfusion injury in rats.
1. Although alpha-tocopherol has been shown to improve renal function following ischaemia-reperfusion (I/R) injury, its clinical use is not common because alpha-tocopherol requires several days of pretreatment to exhibit anti-oxidative benefits. The advent of trolox, a water-soluble analogue of alpha-tocopherol, has raised the possibility that this compound may function more rapidly during acute oxidative stress than the conventional alpha-tocopherol. 2. The present study was undertaken to determine the effects of the short-term administration of trolox on renal excretory function following I/R in rats. 3. Male Wistar rats were subjected to 45 min unilateral renal artery occlusion followed by 120 min reperfusion. The control I/R group was subjected to I/R and received saline as an intravenous bolus (2 mL/kg) followed by a continuous infusion of 2 mL/kg per h starting 30 min before ischaemia, whereas the three trolox-treated I/R groups were given an i.v. bolus of trolox (2.5 mg/kg) followed by a continuous infusion (12 mg/kg per h) starting at 30 min before ischaemia, 5 min before reperfusion and 5 min after reperfusion, respectively. Renal function, malondialdehyde, glutathione and histopathology were evaluated. 4. Ischaemia-reperfusion produced a significant deterioration of renal function, which was accompanied by an elevated malondialdehyde and depleted glutathione content. Kidneys from control I/R rats demonstrated tubular cell transformation, brush border loss, vacuolation, cast formation and tubular obstruction. These changes were attenuated by trolox treatment, with the best improvement achieved when trolox was delivered 5 min before reperfusion. 5. The results demonstrate the renoprotective effects of the short-term administration of trolox on I/R injury. These findings indicate the ability of trolox to overcome a major drawback of using alpha-tocopherol and suggest that trolox may offer a therapeutic advantage over alpha-tocopherol in acute ischaemic renal failure settings.
Wongmekiat
Orawan
O
Department of Physiology, Faculty of Medicine, Chiang Mai University, Chang Mai, Thailand. wongmekiat_yahoo.co.uk
Thamprasert
Kamthorn
K
Lumlertgul
Dusit
D
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008026:Ligation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009318:Natriuresis / Q000187:drug effects; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000601:surgery; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D014554:Urination / Q000187:drug effects
D000975:Antioxidants; D002839:Chromans; D008315:Malondialdehyde; D005978:Glutathione; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid