Toxicological evaluation of azumolene after repeated intraperitoneal administration in rats |
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Authors: | Paula Lima Do Carmo Gisele Zapata‐Sudo Margarete Manhães Trachez Maria Das Graças Fernandes Sales Roberto Takashi Sudo |
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Affiliation: | 1. 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;2. Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil;3. Faculdade de Medicina, Funda??o Técnico Educacional Souza Marques, Ave. Ernani Cardoso 335, Cascadura, Rio de Janeiro, Brazil |
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Abstract: | 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. |
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Keywords: | azumolene dantrolene malignant hyperthermia ryanodine receptor skeletal muscle toxicology |
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