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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Minutoli, Letteria Antonuccio, Pietro Irrera, Natasha Rinaldi, Mariagrazia Bitto, Alessandra Marini, Herbert Pizzino, Gabriele Romeo, Carmelo Pisani, Antonina Santoro, Giuseppe Puzzolo, Domenico Magno, Carlo Squadrito, Francesco Micali, Antonio Altavilla, Domenica
Description	Author Affiliation: Minutoli L ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Antonuccio P ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Irrera N ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Rinaldi M ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Bitto A ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Marini H ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Pizzino G ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Romeo C ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Pisani A ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Santoro G ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Puzzolo D ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Magno C ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Squadrito F ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Micali A ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.)); Altavilla D ( Department of Clinical and Experimental Medicine, University of Messina, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy (L.M., N.I., M.R., A.B., H.M., G.P., F.S.))
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) in wild-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 and morphologic studies were carried out in all groups. TI/R in WT mice significantly increased caspase-1 and interleukin (IL)-1ß 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-1ß and IL-18 mRNA expression, blunted caspase-1 and -3 expression, minor histologic damages, low terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine 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.
File Format	HTM / HTML
ISSN	00223565
Issue Number	3
Volume Number	355
e-ISSN	15210103
Journal	Journal of Pharmacology and Experimental Therapeutics
Language	English
Publisher	American Society for Pharmacology and Experimental Therapeutics
Publisher Date	2015-12-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Testis Research Support, Non-u.s. Gov't Spermatogenesis Male Biosynthesis Discipline Pharmacology Rosaniline Dyes Journal Article Caspase 3 Genetics Nitriles Caspase 1 Interleukin-18 Sulfones Carrier Proteins Inflammasomes Reperfusion Injury Mice, Inbred C57bl Interleukin-1beta Pharmacology Metabolism Drug Effects Mice, Knockout Orchiectomy Pathology Animals Testicular Diseases Discipline Therapeutics Mice Apoptosis
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Pharmacology

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