We investigated the role of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome during testis ischemia and reperfusion injury (TI/R) inwild-type (WT) and NLRP3 knock-out (KO) mice. WT and KO mice underwent 1 hour testicular ischemia followed by 4 hours and 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 (45.5 mg/kg i.p.), or vehicle. Animals were killed with a pentobarbital sodium overdose at 4 hours and 1 and 7 days, and bilateral orchidectomies were performed. Biochemical andmorphologic studies were carried out in all groups. TI/R in WT mice significantly increased caspase-1 and interleukin (IL)-1b 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 terminal deoxynucleotidyl transferase–mediated digoxigenin-deoxyuridine nick-end labeling–positive cells, marked histologic damage, and 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 Brilliant Blue G treated mice showed a significant reduced IL-1b and IL-18 mRNA expression, blunted caspase-1 and -3 expression, minor histologic damages, low terminal deoxynucleotidyl transferase–mediated digoxigenindeoxyuridine nick-end labeling 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.

NLRP3 Inflammasome Involvement in the Organ Damage and Impaired Spermatogenesis Induced by Testicular Ischemia and Reperfusion in Mice

MINUTOLI, Letteria
Primo
;
ANTONUCCIO, Pietro;IRRERA, NATASHA;BITTO, ALESSANDRA;MARINI, Herbert Ryan;PIZZINO, CARMELO GABRIELE;ROMEO, Carmelo;PISANI, Antonina Maria;SANTORO, Giuseppe;PUZZOLO, Domenico;MAGNO, Carlo;SQUADRITO, Francesco
;
MICALI, Antonio Girolamo;ALTAVILLA, Domenica
Ultimo
2015-01-01

Abstract

We investigated the role of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome during testis ischemia and reperfusion injury (TI/R) inwild-type (WT) and NLRP3 knock-out (KO) mice. WT and KO mice underwent 1 hour testicular ischemia followed by 4 hours and 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 (45.5 mg/kg i.p.), or vehicle. Animals were killed with a pentobarbital sodium overdose at 4 hours and 1 and 7 days, and bilateral orchidectomies were performed. Biochemical andmorphologic studies were carried out in all groups. TI/R in WT mice significantly increased caspase-1 and interleukin (IL)-1b 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 terminal deoxynucleotidyl transferase–mediated digoxigenin-deoxyuridine nick-end labeling–positive cells, marked histologic damage, and 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 Brilliant Blue G treated mice showed a significant reduced IL-1b and IL-18 mRNA expression, blunted caspase-1 and -3 expression, minor histologic damages, low terminal deoxynucleotidyl transferase–mediated digoxigenindeoxyuridine nick-end labeling 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.
2015
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3065696
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