In vivo assessment of safety and mechanisms underlying in vitro relaxation induced by Mikania laevigata Schultz Bip. ex Baker in the rat trachea.
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.
Graça
Carlos
C
Department of Pharmacy, Universidade Federal do Pará, Brazil.
Baggio
Cristiane Hatsuko
CH
Freitas
Cristina Setim
CS
Rattmann
Yanna Dantas
YD
de Souza
Lauro Mera
LM
Cipriani
Thales Ricardo
TR
Sassaki
Guilherme Lanzi
GL
Rieck
Lia
L
Pontarolo
Roberto
R
da Silva-Santos
José Eduardo
JE
Marques
Maria Consuelo Andrade
MC
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
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