title: In vivo assessment of safety and mechanisms underlying in vitro relaxation induced by Mikania laevigata Schultz Bip. ex Baker in the rat trachea.
abstract: Mikania laevigata, popularly known in Brazil as "guaco", is largely used in folk medicine against respiratory diseases. However, neither the assessment of the toxicity of "guaco" syrup (GS, used by humans) nor its efficacy or mechanisms of action has been properly investigated. Using in vitro procedures, we showed that the hydroalcoholic extract (HE) from Mikania laevigata induces a concentration-dependent relaxation of rat trachea which does not depend on epithelium-derived substances but involves changes in the cellular mobilization of calcium, perhaps due to a direct effect on membrane potassium channels. In addition, we assessed both oral and intraperitoneal acute toxicity, as well as the oral subchronic and chronic toxicity of GS containing controlled amounts of coumarin, the main biological marker of Mikania laevigata preparations used in humans. The calculated LD(50) of GS after intraperitoneal administration was 0.904 g/kg in mice (both sexes) and 0.967 and 0.548 g/kg in male and female rats, respectively. However, the LD(50) values of GS by the oral route were calculated to be up to 10 g/kg, in both male and female mice and rats. Repeated dose 28- or 90-day oral treatment with GS (75, 150 and 300 mg/kg) did not produce any disturbances in the hematological or biochemical parameters of either male or female rats, nor did it provide evidence of toxicity in the hepatic, renal or pancreatic systems. Besides the mechanistic findings, our results provide evidence of the safety of Mikania laevigata in rodents, even after subchronic and chronic administration, at least in relation to the evaluated parameters.
authors.affiliation: Department of Pharmacy, Universidade Federal do Pará, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Graça
authors.forename: Cristiane Hatsuko
authors.initials: CH
authors.lastname: Baggio
authors.forename: Cristina Setim
authors.initials: CS
authors.lastname: Freitas
authors.forename: Yanna Dantas
authors.initials: YD
authors.lastname: Rattmann
authors.forename: Lauro Mera
authors.initials: LM
authors.lastname: de Souza
authors.forename: Thales Ricardo
authors.initials: TR
authors.lastname: Cipriani
authors.forename: Guilherme Lanzi
authors.initials: GL
authors.lastname: Sassaki
authors.forename: Lia
authors.initials: L
authors.lastname: Rieck
authors.forename: Roberto
authors.initials: R
authors.lastname: Pontarolo
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: da Silva-Santos
authors.forename: Maria Consuelo Andrade
authors.initials: MC
authors.lastname: Marques
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001938:Brazil; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D035742:Mikania / Q000737:chemistry*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D023382:Toxicity Tests, Acute / Q000379:methods; D036401:Toxicity Tests, Chronic / Q000379:methods; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D003374:Coumarins; D010069:Oxadiazoles; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D019789:Tetraethylammonium; C030123:coumarin; D015761:4-Aminopyridine; D000109:Acetylcholine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester