ABSTRACT
Background: The vosoactive effects of proteins isolated from leech saliva and leech homogenate have been the focus of many recent studies because of its therapeutic potential. Possible nonlethal and lethal toxic effects have to be determined before any therapeutic effects could be tested. The general objective is to take the first step in drug design by performing an acute toxicity studyMethods: In this randomized, double-blind trial, Swiss mice were administered subcutaneously with varying doses of leech Hirudinaria manillensis (Lesson) homogenate and observed for possible acute toxicity. Toxidromes appearing within the two-week period after the administration of the substance were noted. Necropsy was performed on all the mice subjects. The LD(50) was computed using the log dose-response probit analysis. The doses (in g/kg body weight) were 3.54, 5.0 and 7.06Results: The LD(50) at Day 2 of Hirudinaria manillensis extract was 4.6124 g/kg body weight. The LD(50) at Day 14 was not obtained, because the test animals incurred mortalities beyond Day 2, which could be explained by a delayed toxicity of the test substance. Mice injected with 7.06 g/kg showed the most number of observable toxidromes, involving several organ systems, which generally had an early onset and persisted until the time of death of the mice. Mice treated with 3.54 g/kg showed toxidromes with early onset time, but they were not as consistent as the highest dose and the effects were generally not long-lasting. Motor activity was the most affected among the toxidromes. Gross pathologic findings revealed that the intestine, liver, heart, stomach, lungs and kidney are the commonly affected organs, which had marked changes in all dose groupsConclusions: The crude H. manillensis leech extract caused toxicity in mice, with toxidromes involving mainly the nervous system, specifically the somatosensory and neuromuscular systems. The LD(50) could not be determined in this study. However, using the data at Day 2, LD(50) was 4.6124 g/kg body weight. The LOAEL could be less than or equal to 3.54 g/kg body weight. No observable adverse effect level could not be determined. (Author)