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Abstract :
[en] Background: Experimental aristolochic Acid nephropathy (AAN) is a pertinent model of tubulo-interstitial nephritis characterized by an early phase of acute kidney injury (AKI) leading to progressive fibrosis and chronic kidney disease (CKD). Here, the present model was used to determine the role of AMPK in renal outcome and its involvement in the AKI-to-CKD transition. Methods: C57BL/6J male mice were randomly subjected to i.p. injection of either sterile saline solution, AA, AA+AICAR (the specific AMPK activator) for 4 days. Mice were then euthanized either at day 5 or day 20. Results: AA-treated mice displayed loss of renal function, as reflected by significant increases in plasma creatinine level and proteinuria at days 5 and 20. In addition, impairment of tubular cells was also observed by the significant increase in urinary excretion of lysosomal enzyme N-acetyl-ß-D-glucosaminidase in AA-treated mice. These changes were
prevented by AICAR treatment. To further determine the role of AMPK in AA-induced oxidative stress, Nox1, 2 and 4 were investigated at the mRNA levels. No changes were observed for Nox1 and 4. However, Nox2 was significantly increased in AA-treated mice while this rise was prevented by AICAR treatment at day 5 but not at day 20. Moreover, the urinary hydrogen peroxide level, a stable product of ROS production, was significantly higher after AA intoxication and reduced with AICAR. Regarding inflammation, AA mice exhibited a significant increase in MCP-1 mRNA level. This rise was only prevented by AICAR at day 5. Finally, at day 5, there was no significant macrophage infiltration with AICAR while at day 20, this significant increase was not prevented by AICAR. Conclusions: These findings show a beneficial effect of AMPK in AA-induced AKI. In view of these data, we suggest that chronic AICAR treatment is necessary for complete nephroprotection and recovery. The activation of AMPK represents a potential strategy to prevent the transition from AKI-to-CKD.
