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2015 ; 5
(ä): 15482
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Endogenously elevated bilirubin modulates kidney function and protects from
circulating oxidative stress in a rat model of adenine-induced kidney failure
#MMPMID26498893
Boon AC
; Lam AK
; Gopalan V
; Benzie IF
; Briskey D
; Coombes JS
; Fassett RG
; Bulmer AC
Sci Rep
2015[Oct]; 5
(ä): 15482
PMID26498893
show ga
Mildly elevated bilirubin is associated with a reduction in the presence and
progression of chronic kidney disease and related mortality, which may be
attributed to bilirubin's antioxidant properties. This study investigated whether
endogenously elevated bilirubin would protect against adenine-induced kidney
damage in male hyperbilirubinaemic Gunn rats and littermate controls. Animals
were orally administered adenine or methylcellulose solvent (vehicle) daily for
10 days and were then monitored for 28 days. Serum and urine were assessed
throughout the protocol for parameters of kidney function and
antioxidant/oxidative stress status and kidneys were harvested for histological
examination upon completion of the study. Adenine-treated animals experienced
weight-loss, polyuria and polydipsia; however, these effects were significantly
attenuated in adenine-treated Gunn rats. No difference in the presence of
dihydroadenine crystals, lymphocytic infiltration and fibrosis were noted in Gunn
rat kidneys versus controls. However, plasma protein carbonyl and F2-isoprostane
concentrations were significantly decreased in Gunn rats versus controls, with no
change in urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine or kidney tissue
F2-isoprostane concentrations. These data indicated that endogenously elevated
bilirubin specifically protects from systemic oxidative stress in the vascular
compartment. These data may help to clarify the protective relationship between
bilirubin, kidney function and cardiovascular mortality in clinical
investigations.