title: In vivo participation of nitric oxide in hyperproliferative epidermal phenomena in mice.
abstract: A significant involvement of nitric oxide (NO) in the process of keratinocyte proliferation is reported with many divergences. To determine the involvement of NO in the hyperproliferative process of epidermis in vivo, non-selective inhibitor (N(G)-nitro-L-arginine-methyl ester.HCl: L-NAME) and selective inhibitors for inducible NO synthase (iNOS) and neuronal NO synthase (nNOS) (Aminoguanidine: AG and 7-Nitroindazole: 7-NI, respectively) and a NO-donor (Sodium nitroprusside: SNP) were topically applied twice a day in mice ear treated with multiple applications of croton oil. L-NAME and 7-NI treatments decreased and SNP increased ear edema formation. However, ear weight was reduced in groups that received L-NAME and 7-NI, while the AG and SNP groups presented an increment. The histological evaluation of epidermis thickness showed that all NOS inhibitors were able to prevent the increase in epidermis width caused by croton oil, while SNP contributed to enlargement. The same results were observed in the PCNA staining, where treatments with NOS inhibitors caused a reduction in the number of cells in the epidermis, while SNP caused an enhancement. 7-NI treatment reduced polymorphonuclear and mononuclear leukocytes migration when compared to the control group. The AG application increased the migration of polymorphonuclear and mononuclear cells, while the SNP enhanced only the polymorphonuclear cells. Therefore, in the skin NO produced by nNOS is involved in the control of keratinocyte hyperproliferation, with the contribution of iNOS. In the animal model of cutaneous chronic inflammation by croton oil, NO is involved in the exudation and leukocyte migration, with participation of all three enzymes.
authors.affiliation: Department of Pharmacology, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Daniel Augusto Gasparin Bueno
authors.initials: DA
authors.lastname: Mendes
authors.forename: Cintia Delai da Silva
authors.initials: CD
authors.lastname: Horinouchi
authors.forename: Arthur da Silveira
authors.initials: Ada S
authors.lastname: Prudente
authors.forename: Bruna da Silva
authors.initials: Bda S
authors.lastname: Soley
authors.forename: Jamil
authors.initials: J
authors.lastname: Assreuy
authors.forename: Michel Fleith
authors.initials: MF
authors.lastname: Otuki
authors.forename: Daniela Almeida
authors.initials: DA
authors.lastname: Cabrini
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003436:Croton Oil; D003877:Dermatitis, Contact / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006146:Guanidines / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D003907:Dexamethasone; D003436:Croton Oil; D009195:Peroxidase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D000118:Acetylglucosaminidase; C004479:pimagedine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester