TITLE:
The gene expression of adenosine receptors in the processes of contrast induced nephropathy in mouse kidney
AUTHORS:
Luyu Yao, Cynthia Zhao, Xin Gu, Gopi K. Kolluru, Christopher G. Kevil, Wayne W. Zhang
KEYWORDS:
Contrast Induced Nephropathy; Adenosine Receptor; Iodixanol
JOURNAL NAME:
World Journal of Cardiovascular Diseases,
Vol.3 No.9,
December
23,
2013
ABSTRACT:
Objective: Contrast induced nephropathy (CIN) is the
third leading cause of hospital acquired renal failure. The mechanism of CIN is
not fully understood. The objectives of this study were to investigate the
expression changes of the four subtypes of adenosine receptors (A1AR,
A2AAR, A2BAR, and A3AR) following
administration of contrast media in mice. Methods: C57BL/6J mice were
randomized into treatment and control groups. Iodixanol (IDX) was administered
to two treatment groups through retroorbital injection at two different
dosages, 0.75 gI/kg and 2.75 gI/kg. Phosphate buffered saline (PBS) was given
to the control group. Mice kidneys were harvested at day 3 and day 7 after Iodixanol
administration. Kidney injuries and function were evaluated according to
Hematoxylin and eosin stain, Ki67 protein expression, and TUNEL assay of
paraffin embedded kidney sections, and plasma creatinine assay. RNA and protein
were extracted from the kidney specimens. A1AR, A2AAR, A2BAR,
and A3AR RNA and protein level of the samples were assessed using
qRT-PCR and Western blotting, with GAPDH as an endogenous control. Results:
H&E staining showed no significant histopathology injuries after Iodixanol
administration. No evidence of kidney injury and functional impairment was
found. However, there was an increased number of A1AR, A2AAR,
A2BAR, and A3AR RNA transcripts detected in the kidney 3
days after Iodixanol injection. The RNA levels in all the four subtypes of
adenosine receptors were increased 2-3 fold in the day 3 specimens and back to
normal at day 7. Western blot demonstrated that A1AR, A2AAR,
and A3AR expression increased 1.5 to 2 fold at day 3 and day 7
following Iodixanol injection. A2BAR baseline expression was low in
normal physiological conditions and no significant change was detected by
Western blot. Conclusions: Iodixanol significantly increases adenosine
receptors gene expression in mice. This suggests that adenosine receptors may
play a role in the development of CIN.