[Long-term toxicity test of arginine esterase from Agkistrodon halys ussuriensis venom].
To study the long-term toxicity of arginine esterase from Agkistrodon halys ussuriensis venom for the clinical application of arginine esterase in the future. Beagle dogs were used as experimental animals and were divided into control group, arginine esterase low dose group (0.06 u/kg), the middle dose group (0.18 u/kg) and high dose group (0.36 u/kg). Every group consisted of four dogs. The arginine esterase was given intravenously once a day for 180 days. Then three dogs in each group were sacrificed and the fourth one was fed without injecting arginine esterase for 15 days. The toxic reactions during treatment and recovery period were determined by evaluating and comparing the general criteria ( including locomotor activity, growth rate, appetite and death rate), clinical criteria (including blood test and urine test), pathological dissection and viscera coefficient of the treated animals and the control animals. There were no significant differences in general criteria. The clinical criteria of the treated animals were the same as those of the control animals except liver function. There were no significant differences in pathological dissection and viscera coefficient between the treated animals and the control animals except livers. The livers in high dose arginine esterase treated animals were swollen and vacuolated and there was significant difference in liver coefficient between them (P<0.05). The toxic symptom of liver disappeared after withdrawal of treatment. From these results, the non-toxic dose of arginine esterase for dogs was estimated to be 0.18 u/kg under the present study conditions and is about 15 times the clinical dosage for using the drug "Qingshuanmei" of which the main component is arginine esterase. The long-term toxicity test result indicates that the toxicity of pure arginine esterase is lower than that of "Qingshuanmei", suggesting that clinical use of the arginine esterase is safe.
Wei
Chuanbao
C
College of Life Science, Zhejiang University, Hangzhou 310027.
Chen
Fei
F
D000818:Animals; D000925:Anticoagulants / Q000633:toxicity*; D002265:Carboxylic Ester Hydrolases / Q000633:toxicity*; D003435:Crotalid Venoms / Q000201:enzymology* / Q000633:toxicity; D004285:Dogs; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male
C031442:Agkistrodon venoms; D000925:Anticoagulants; D003435:Crotalid Venoms; C019724:arginine esterase; D002265:Carboxylic Ester Hydrolases