title: Evidence for a role of mitogen-activated protein kinase 3/mitogen-activated protein kinase in the development of testicular ischemia-reperfusion injury.
abstract: Mitogen-activated protein kinase (MAPK) 3/MAPK1 (also known as ERK1/ERK2) plays an important role in the signal transduction pathways. To our knowledge, however, its role in the development of testicular ischemia-reperfusion injury has not yet been investigated. Therefore, we studied the pattern of MAPK3/MAPK1 activation in a experimental model of testicular ischemia-reperfusion injury. We also investigated MAPK8 to understand whether an association exists between these two MAPKs. Adult male Sprague-Dawley rats were subjected to 1 h of testicular ischemia followed by 24 h of reperfusion or to a sham testicular ischemia-reperfusion. Animals were randomized to receive PD98059, which is an inhibitor of MAPK3/MAPK1 (10 mg/kg i.p. administered immediately after detorsion), or its vehicle. The time course of MAPK3/MAPK1, MAPK8, and tumor necrosis factor (TNF; also known as TNF alpha) expression and a histological examination in both the ischemic-reperfused testis and the contralateral one were performed. In both testes, MAPK3/MAPK1 and MAPK8 expression appeared following 10 min of reperfusion and reached their highest activation after 30 min. The MAPK levels slowly decreased, and no significant expression of either kinase was observed following 2 h of reperfusion. Expression of TNF was evident after 1 h of reperfusion and reached its maximum increase after 3 h. PD98059 blunted MAPK3/MAPK1 and MAPK8, reduced TNF expression, and improved the testicular damage caused by ischemia-reperfusion injury in both testes. These data emphasize that MAPK3/MAPK1 has a role in testicular damage and that its blockade might have a future therapeutic role for the management of patients with unilateral testicular torsion.
authors.affiliation: Department of Experimental and Clinical Medicine and Pharmacology, University of Messina, Italy. leaminutoli@libero.it
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Pietro
authors.initials: P
authors.lastname: Antonuccio
authors.forename: Carmelo
authors.initials: C
authors.lastname: Romeo
authors.forename: Piero Antonio
authors.initials: PA
authors.lastname: Nicòtina
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Salvatore
authors.initials: S
authors.lastname: Arena
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Nunzio
authors.initials: N
authors.lastname: Turiaco
authors.forename: Antonio
authors.initials: A
authors.lastname: Cutrupi
authors.forename: Biagio
authors.initials: B
authors.lastname: Zuccarello
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004487:Edema / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D013733:Testicular Diseases / Q000188:drug therapy / Q000378:metabolism*; D013737:Testis / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one