In situ detection of lipid peroxidation by-products as markers of renal ischemia injuries in rat kidneys.
OBJECTIVE
Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes. In renal transplantation, this mechanism is triggered by ischemia/reperfusion and may be of relevance in graft failure.


METHODS
Using specific antibodies directed against malondialdehyde (MDA) and 4-hydroxynonenal (HNE) adducts, major aldehydic metabolites of lipid peroxidation, we investigated, in situ, by means of an immunohistochemical procedure, the occurrence of lipid peroxidation during different warm ischemic periods of 0, 15, 30, 45 and 60 minutes in rat kidneys prior to reperfusion. The same experiments included followup of the rats after nephrectomy and reperfusion for 10 days.


RESULTS
We observed superficial and deep cortex immunostaining with both antibodies against MDA and HNE after 30 minutes of warm ischemia. This immunostaining was observed in the absence of any histological lesions, as assessed by routine staining. After 45 and 60 minutes of warm ischemia, lipid peroxidation byproducts were detected both in the cortex and in the medulla, which is associated with 33% and 66% of rat deaths respectively.


CONCLUSIONS
This study confirms the involvement of the lipid peroxidation process in kidney damage during anoxia before reperfusion, and its extension to the whole organ. Lipid peroxidation byproducts were detectable in warm ischemic kidney, and the presence of medulla immunostaining was associated with the animals' death. Lipid peroxidation immunostaining might thus be useful as a sensitive tool to detect ischemic damage after warm ischemia prior to reperfusion, as well as in the decision to carry out kidney transplantation in humans.
Laboratoire de Chirurgie Expérimentale, Faculté de Médecine Paris-Sud, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
P
P
Eschwège
V
V
Paradis
M
M
Conti
A
A
Holstege
F
F
Richet
J
J
Detève
P
P
Ménager
A
A
Legrand
A
A
Jardin
P
P
Bedossa
G
G
Benoit
D000447:Aldehydes / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000447:Aldehydes; D015415:Biomarkers; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal