Khurrum Shahzad, Fabian Bock, Moh'd Mohanad Al-Dabet, Ihsan Gadi, Shrey Kohli, Sumra Nazir, Sanchita Ghosh, Satish Ranjan, Hongjie Wang, Thati Madhusudhan, Peter P Nawroth, Berend Isermann
Glomerular apoptosis may contribute to diabetic nephropathy (dNP), but the pathophysiologic relevance of this process remains obscure. Here, we administered two partially disjunct polycaspase inhibitors in 8-week-old diabetic (db/db) mice: M-920 (inhibiting caspase-1, -3, -4, -5, -6, -7, and -8) and CIX (inhibiting caspase-3, -6, -7, -8, and -10). Notably, despite reduction in glomerular cell death and caspase-3 activity by both inhibitors, only M-920 ameliorated dNP. Nephroprotection by M-920 was associated with reduced renal caspase-1 and inflammasome activity...
August 2016: Journal of the American Society of Nephrology: JASN