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RENOPROTECTIVE EFFECT OF TROLOX AGAINST ISCHAEMIA–REPERFUSION INJURY IN RATS
Author(s) -
Wongmekiat Orawan,
Thamprasert Kamthorn,
Lumlertgul Dusit
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04651.x
Subject(s) - trolox , malondialdehyde , bolus (digestion) , ischemia , oxidative stress , medicine , renal function , reperfusion injury , anesthesia , pharmacology , chemistry , urology , endocrinology , antioxidant capacity
SUMMARY1 Although α‐tocopherol has been shown to improve renal function following ischaemia–reperfusion (I/R) injury, its clinical use is not common because α‐tocopherol requires several days of pretreatment to exhibit anti‐oxidative benefits. The advent of trolox, a water‐soluble analogue of α‐tocopherol, has raised the possibility that this compound may function more rapidly during acute oxidative stress than the conventional α‐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 α‐tocopherol and suggest that trolox may offer a therapeutic advantage over α‐tocopherol in acute ischaemic renal failure settings.