Endogenously elevated bilirubin modulates kidney function and protects from circulating oxidative stress in a rat model of adenine-induced kidney failure.
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.
Heart Foundation Research Centre, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
Ai-Ching
AC
Boon
School of Medicine and Cancer Molecular Pathology, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.|Pathology Queensland, Gold Coast University Hospital, Gold Coast, Australia.
Alfred K
AK
Lam
School of Medicine and Cancer Molecular Pathology, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
Vinod
V
Gopalan
Department of Health Technology &Informatics, The Hong Kong Polytechnic University, Hong Kong.
Iris F
IF
Benzie
School of Human Movement and Nutrition Sciences, University of Queensland, St Lucia, Australia.
David
D
Briskey
School of Human Movement and Nutrition Sciences, University of Queensland, St Lucia, Australia.
Jeff S
JS
Coombes
School of Human Movement and Nutrition Sciences, University of Queensland, St Lucia, Australia.
Robert G
RG
Fassett
Heart Foundation Research Centre, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
Andrew C
AC
Bulmer
D000225:Adenine / Q000009:adverse effects*; D000818:Animals; D001663:Bilirubin / Q000097:blood*; D007677:Kidney Function Tests; D018384:Oxidative Stress; D051381:Rats; D011911:Rats, Gunn; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000209:etiology* / Q000378:metabolism
D000225:Adenine; D001663:Bilirubin