TY - JOUR T1 - NLRP3 inflammasome involvement in the organ damage and impaired spermatogenesis induced by testicular ischemia and reperfusion in mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.115.226936 SP - jpet.115.226936 AU - Letteria Minutoli AU - Pietro Antonuccio AU - Natasha Irrera AU - Mariagrazia Rinaldi AU - Alessandra Bitto AU - Herbert Marini AU - Gabriele Pizzino AU - Carmelo Romeo AU - Antonina Pisani AU - Giuseppe Santoro AU - Domenico Puzzolo AU - Carlo Magno AU - Francesco Squadrito AU - Antonio Micali AU - Domenica Altavilla Y1 - 2015/01/01 UR - http://jpet.aspetjournals.org/content/early/2015/09/25/jpet.115.226936.abstract N2 - We investigated the role of NLRP3 inflammasome during testis ischemia and reperfusion injury (TI/R) in wild type (WT) and NLRP3 knock-out (KO) mice. WT and KO mice underwent 1 hour testicular-ischemia followed by 4 hours, 1 and 7 days of reperfusion or a sham TI/R. Furthermore, two groups of WT mice were treated, at the beginning of reperfusion and up to 7 days, with two inflammasome inhibitors, BAY 11-7082 (20 mg/kg i.p.), or Brilliant Blue G (BBG; 45.5 mg/kg i.p.) or vehicle. Animals were killed with a pentobarbital sodium overdose at 4 hours, 1 and 7 days and bilateral orchidectomies were performed. Biochemical and morphological studies were carried out in all groups. TI/R in WT mice significantly increased caspase-1 and IL-1β mRNA after 4 hours, and IL-18 mRNA at 1 day of reperfusion (p ≤ 0.05); there was also a significant increase in caspase-3 and in TUNEL-positive cells, a marked histological damage, and an altered spermatogenesis in WT mice in both testes after 1 and 7 days of reperfusion. KO TI/R mice, WT TI/R BAY 11-7082 and BBG treated mice showed a significant reduced IL-1β and IL-18 mRNA expression, blunted caspase-1 and -3 expression, minor histological damages, low TUNEL activity and preserved spermatogenesis. These data suggest that the activation of NLRP3 plays a key role in TI/R and its inhibition might represent a therapeutic target for the management of patients with unilateral testicular torsion. ER -