RESUMO
Oxygen-derived free radicals [OFR] involvement in ischaemia-reperfusion [IR] injury was investigated in a rat isolated kidney model, using 20 minutes ischaemia followed by 15 or 60 minutes reperfusion. Two antioxidants, the xanthine oxidase inhibitor altopurinol and the hydroxyl radical scavenger dimethylthiourea [DMTU], were used to try and prevent OFR-related damage. Renal function was estimated from the inulin clearance, fractional sodium excretion and renal vascular resistance. iocation and extent of tubular damage, and type of cell death [apoptosis vs necrosis] were used as morphological parameters of IR-induced change Cell damage was most extensive in the nephron segments of the outer zone of the outer medulla [straight proximal tubule and thick ascending limb [TAL]]. Pre-treatment with allopurinol or DMTU did not improve renal function. Less structural damage was observed in the TAL of allopuriol - or DMTU - treated kidneys compared with IR alone. In allopurinol - treated kidneys, luminal debris was less extensive than that seen in IR kidneys. Most cell death was necrotic in type and morphological features of apoptosis were seen infrequently. The beneficial effects of allopurinol and DMTU on structural change did not correlate with functional improvement during the reperfusion period This may require longer reperfusion or multiple treatments. The results suggest that OFR - injury is of limited significance in this model of renal IR injury. Targeting OFR injury may only be useful after very brief periods of ischacmia where necrosis is minimal and the potential for recovery is greater. The results confirm the different susceptibilites of individual nephron segments to injury within the intact kidney. Understanding the molecular response to injury in each segment should facilitate development of methods to accelerate repair after IR injury