UNASSIGNED: Necroptosis is a nonapoptotic cell death pathway. We aim to study the effect of @entity19536 (a specific necroptosis inhibitor) in @entity900 -induced injury. We analyzed the effect of the combined use of inhibitors of apoptosis (z-vad) and necroptosis ( @entity19536 ) in @entity810 by @entity900 in @entity1 proximal tubule cells. Our results showed moderate effectiveness in cytoprotection after treatment with z-vad. But the concomitant use of inhibitors (z-vad and @entity19536 ) presented synergistic and additive protection. The present study analyzed the @entity522 activity and we observed a significant decrease in the group treated with z-vad and @entity900 . However we did not observe changes in the group treated with both inhibitors (z-vad and @entity19536 ) and @entity900 . Thus, demonstrating that necroptosis is a caspase-independent mechanism. We also analyzed the effect of @entity19536 in vivo model. C57BL/6 @entity19 were treated with @entity900 and/or inhibitors. The concomitant use of inhibitors (z-vad and @entity19536 ) recovered renal function and decreased levels of urinary Ngal. Additionally, we analyzed the expression of @entity5398 , a specific marker for necroptosis. In animals treated with @entity900 and z-VAD levels of @entity5398 were higher. This result reinforces that necroptosis occurs only in conditions where apoptosis was blocked. However, the use of both inhibitors (z-vad and @entity19536 ) provided additional protection. In conclusion, our study has a significant potential to show in vitro and in vivo protection obtained by @entity19536 . Therefore, our results suggest that necroptosis may be an important mechanism of cell death after @entity8 .

Synergistic effect of apoptosis and necroptosis inhibitors in XXXX -induced nephrotoxicity.

@entity1 :: ('9606', 'Species') :: ['human'] @entity19536 :: ('MESH:C507699', 'Chemical') :: ['necrostatin-1'] @entity8 :: ('MESH:D007674', 'Disease') :: ['kidney injury'] @entity522 :: ('836', 'Gene') :: ['caspase-3'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity810 :: ('MESH:D058186', 'Disease') :: ['acute kidney injury'] @entity5398 :: ('8737', 'Gene') :: ['RIP-1']
@entity900 :: (MESH:D002945,Chemical) :: ['cisplatin']
