Time course and attenuation of ischaemia-reperfusion induced oxidative injury by propofol in human renal transplantation

Abstract

Ischaemia-reperfusion injury resulting from interruption and restoration of blood flow might be related to free radical mediated oxidative stress and inflammation, and subsequently to post-surgery related complications. We studied the impact of renal transplantation on oxidative stress and inflammation by measuring F₂-isoprostanes and prostaglandin F_2α, respectively, during transplantation and post-surgery. Additionally, due to earlier observations, two dissimilar anaesthetic agents (thiopentone and propofol) were compared to determine their antioxidative capacity rather than their anaesthetic properties. Blood samples were collected before, post-intubation, immediately, 30, 60,120, 240 min, and 12 and 24 h after reperfusion. Oxidative stress and inflammatory response were detected by measuring 8-iso-PGF_2α (a major F₂-isoprostane and a biomarker of oxidative stress) and 15-keto-dihydro-PGF_2α (a major metabolite of PGF_2α and a biomarker of COX-mediated inflammatory response), respectively. Reperfusion of the transplanted graft significantly increased plasma levels of 8-iso-PGF_2α. PGF_2α metabolite levels, although elevated, did not reach statistical significance. In addition, significantly lower levels of 8-iso-PGF_2a were observed in the propofol group compared to the thiopentone group. Together, these findings underline an augmented oxidative stress activity following an inflammatory response after human renal transplantation. Furthermore, propofol a well-known anaesthetic, counteracted oxidative stress by lowering the formation of a major F₂-isoprostane.