engleski

In vivo determination of test concentration for tested compound based on „Up and down„ method

Pharmacology testing of new compound implies determination of toxicity and genotoxicity following potential antimicrobial, antitumor or some other healing effects. Pharmacology evaluation usually needs results of in vivo testing on different animal models. The most used animal model is mouse model because of strong physiological resemblance with humans. Design of animal model must be conceived on the way that necessary answers about desirable and undesirable characteristics of the test compound gain on the smallest possible number of animals1. Toxic evaluation requires determination of non-lethal test concentration for investigating compound. One of recommended methods for toxicity studies is “Up and down” procedure2. In this work a highly inbreed strain of male mice (n=12) on mixed genetic background from strains C57BL/6J and 129S1/SvImJ. Was used. We tested two new monomethine cyanine derivatives (MCD 4, 8) in concentration range from 3.5 ; 7.0 ; 15.0, and 30.0 mg/kg (MCD 4) and 3.5 as wee as 7.0 mg/kg (MCD 8) diluted in saline (0.9% NaCl). Mouse survival 24 h after intra peritoneal (i.p.) application was monitored. Test mouse are further subdued to the time and concentration tolerance test for the period of 40 days. On the thirteenth and twenty six day test animals received 2nd and 3rd application of test concentration. Every day they are monitored for their behaviour and weighted. During test period mouse treated with MCD 4 at the concentration of 15 and 30 mg/kg died followed by average loss of body weight by 18.55% and 32.26% respectively. Mice treated with smaller test concentrations of MCDs survive 40 days test period. According to obtained results concentration of 7.0 mg/kg is selected as concentration for further acute and chronic toxicology study.

animal model; test concentration;

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