Anisodamine exerts significant protective effect on
ischemia/reperfusion (I/R) injury in various organs. However, little is known about the mechanisms of
anisodamine in renal I/R injury. Activation of extracellular regulated
protein kinases (ERK) pathway promotes the repair of renal epithelial cells following
oxidant injury. The present study investigated whether the renoprotective role of
anisodamine against renal I/R injury in rats was associated with the activation of ERK signaling pathway. Male Sprague-Dawley (SD) rats were separated into the following groups:
Sham-operated group, I/R group,
anisodamine-treated group,
PD98059 (
MEK-1/ERK inhibitor)-treated group and
anisodamine plus PD98059-treated group. A rat model of renal I/R was established by excising the right kidney and then clamping the left renal pedicle for 45 min followed by reperfusion for 24 h. Serum and renal tissue samples were obtained for assays of the associated morphological, molecular and biochemical parameters. Treatment with
anisodamine ameliorated renal I/R injury, as evidenced by improvements of renal histology and kidney function, a decrease in paller's score and apoptosis index.
Anisodamine also upregulated the phosphorylation levels of ERK1/2 and its downstream targets, including 90 ribosomal
S6 kinase (p90rsk) and Bad, as well as the expression of antiapoptotic Bcl-2
protein, downregulated the expression levels of proapoptotic
proteins Bax and cleaved-caspase-3, whereas these effects were greatly abolished by administration of
PD98059. In conclusion, the results suggest that
anisodamine prevents renal I/R injury in rats as a result of an activation of the ERK signaling pathway and anti-apoptotic properties.