Toxicological evaluation of azumolene after repeated intraperitoneal administration in rats.
We investigated the toxicity of azumolene (Az), a more water-soluble compound than dantrolene, after 14 days of intraperitoneal (i.p.) administration in rats at doses of 1, 2.5 or 10 mg/kg/day. No animals died or presented signs of toxicity. No significant differences in water and food consumption or weight gain were noted among the groups. Blood analysis revealed no significant alteration by Az treatment in the number of blood cells. However, Az treatment induced a perivascular inflammatory reaction in the liver and non-diffuse necrosis of skeletal muscle, both of which occurred only at the highest dose of Az and were completely reversed 14 days after cessation of treatment. Congestion and inflammation in the kidneys were only partially reversed. Caffeine-induced contracture of skeletal muscle was not altered during 7 days of i.p. injection of Az (2.5 mg/kg/day). In conclusion, Az is a safe compound for long-term administration, but does cause a mild, reversible reaction in skeletal muscle and kidney.
do Carmo
Paula Lima
PL
Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av Carlos Chagas 373, Sala 14, Bloco J, Centro de Ciências da Saúde, Cidade Universitária, Rio de Janeiro, Brazil.
Zapata-Sudo
Gisele
G
Trachez
Margarete Manhães
MM
das Graças Fernandes Sales
Maria
M
Sudo
Roberto Takashi
RT
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000737:chemistry / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009465:Neuromuscular Agents / Q000737:chemistry / Q000633:toxicity*; D010080:Oxazoles / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D036401:Toxicity Tests, Chronic
D007093:Imidazoles; D009465:Neuromuscular Agents; D010080:Oxazoles; D002110:Caffeine; C061387:azumolene