Luyu Yao1, Gopi K. Kolluru2, Kevil G. Christopher2, Wayne W. Zhang1
1Louisiana State University Health Sciences Center, Surgery Department, Shreveport, LA; 2Louisiana State University Health Sciences Center, Pathology Department, Shreveport, LA.
OBJECTIVES: Contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal failure, which is a common complication following endovascular surgery procedures. The mechanism of CIN is not fully understood. Adenosine receptors (AR) regulate various physiological activities in kidney. We hypothesized that adenosine and its receptors may play a role in development of CIN. 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 agent in mice.
METHODS: C57B1/6J mice were randomized to treatment and control groups. Iodixanol, a commonly used contrast agent, was administered to treatment groups through retro-orbital injection at two different dosages, 0.75gI/kg and 2.75gI/kg. PBS was given to the mice in control group. Mice kidneys were harvested at day 3 and day 7 following iodixanol administration. RNA and protein were then extracted. qRT -PCR and Western blot were used to quantify A1AR, A2AAR, A2BAR and A3AR RNA and protein expression respectively, with GAPDH as endogenous control.
RESULTS: qRT-PCR showed that iodixanol induced AR transcription, specifically in the group treated with 2.75gI/kg at day 3 after injection. The RNA levels in all the four subtypes of ARs were increased 2-3 folds at day 3, but returned to normal at day 7 in iodixanol groups compared to PBS controls. The Western blot results showed that A1AR, A2AAR and A3AR expressions were increased 1.5-2 folds in iodixanol group at day 3 compared to PBS control. A2BAR expression was very low in normal physiological condition, and no significant changes were detected by western blot.
CONCLUSIONS: Our results indicate that iodixanol induces adenosine receptor gene expression in mice. Adenosine receptors may play a role in the development of CIN. Further investigation on the correlation between adenosine receptor gene expression and severity of CIN will be performed.
AUTHOR DISCLOSURES: K. G. Christopher: Nothing to disclose; G. K. Kolluru: Nothing to disclose; L. Yao: Nothing to disclose; W. W. Zhang: Nothing to disclose.
Posted April 2013