title: Ionic imbalance and lack of effect of adjuvant treatment with methylene blue in the hamster model of leptospirosis.
abstract: Leptospirosis in humans usually involves hypokalaemia and hypomagnesaemia and the putative mechanism underlying such ionic imbalances may be related to nitric oxide (NO) production. We previously demonstrated the correlation between serum levels of NO and the severity of renal disease in patients with severe leptospirosis. Methylene blue inhibits soluble guanylyl cyclase (downstream of the action of any NO synthase isoforms) and was recently reported to have beneficial effects on clinical and experimental sepsis. We investigated the occurrence of serum ionic changes in experimental leptospirosis at various time points (4, 8, 16 and 28 days) in a hamster model. We also determined the effect of methylene blue treatment when administered as an adjuvant therapy, combined with late initiation of standard antibiotic (ampicillin) treatment. Hypokalaemia was not reproduced in this model: all of the groups developed increased levels of serum potassium (K). Furthermore, hypermagnesaemia, rather than magnesium (Mg) depletion, was observed in this hamster model of acute infection. These findings may be associated with an accelerated progression to acute renal failure. Adjuvant treatment with methylene blue had no effect on survival or serum Mg and K levels during acute-phase leptospirosis in hamsters.
authors.affiliation: Centro de Pesquisa Gonçalo Moniz-Fiocruz, Salvador, BA, Brasil.
authors.forename: Cleiton Silva
authors.initials: CS
authors.lastname: Santos
authors.forename: Everton Cruz de
authors.initials: EC
authors.lastname: Azevedo
authors.forename: Luciane Marieta
authors.initials: LM
authors.lastname: Soares
authors.forename: Magda Oliveira Seixas
authors.initials: MO
authors.lastname: Carvalho
authors.forename: Andréia Carvalho
authors.initials: AC
authors.lastname: dos Santos
authors.forename: Adenizar Delgado
authors.initials: AD
authors.lastname: das Chagas
authors.forename: Caroline Luane Rabelo
authors.initials: CL
authors.lastname: da Silva
authors.forename: Ursula Maira Russo
authors.initials: UM
authors.lastname: Chagas
authors.forename: Mitermayer Galvão
authors.initials: MG
authors.lastname: dos Reis
authors.forename: Daniel Abensur
authors.initials: DA
authors.lastname: Athanazio
mesh_terms: D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D006162:Guanylate Cyclase / Q000187:drug effects; D007473:Ion Channels / Q000097:blood*; D007922:Leptospirosis / Q000097:blood / Q000188:drug therapy*; D008274:Magnesium / Q000097:blood; D008751:Methylene Blue / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000097:blood; D011188:Potassium / Q000097:blood; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D012964:Sodium / Q000097:blood; D000071756:Soluble Guanylyl Cyclase
chemical_list: D007473:Ion Channels; D009589:Nitrogen Oxides; D018160:Receptors, Cytoplasmic and Nuclear; D012964:Sodium; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D008274:Magnesium; D011188:Potassium; D008751:Methylene Blue