Ischemia/reperfusion (I/R) is one of the main causes of acute renal failure, leading to generation of reactive oxygen species (ROS) and ensuing oxidative stress, which results in unfolded/misfolded protein accumulation and its dependent response pathways,generally known as unfolded protein response (UPR), in the endoplasmic reticulum (ER). We studied the effects of renal I/R on the expression of ER-stress genes, as well as concomitant effects of oral pretreatment with pomegranate (Punica granatum L.) pith and carpellary membrane (PPCM). An in vivo model of rat kidney I/R followed by conventional and real-time RT-PCR was used to evaluate the modulation of GRP78 and XBP1 as central UPR and ER-stress markers. Ischemia followed by reperfusion (60 and 150 min, respectively) resulted in decreased antioxidant properties of plasma (lowered ferric reducing ability of plasma [FRAP] value) and GRP78 transcript levels. Oral administration of PPCM aqueous extract for 10 days with or without ischemia (PPCM and PPCM/Isc groups, respectively) was able to further decrease the GRP78 expression, while it increased the FRAP value. PPCM pretreatment also reduced the XBP1 splicing in the PPCM/Isc group compared to the Isc group. These results suggest that UPR is activated during oxidative insults induced by I/R, while PPCM can reduce I/R-induced ER stress in rat kidneys via antioxidant defense mechanisms.

Keywords