Role of reactive oxygen species in the chemoprophylactic action of methyl [5-[[4-(2-pyridinyl)-1-piperazinyl]-carbonyl]-1H-benzimidazol-2 yl] carbamate in hamster against Ancylostoma ceylanicum.
To delineate mechanisms involved in the prophylactic action of methyl [5-[[4-(2-pyridinyl)-1-piperazinyl]-carbonyl]-1H-benzimidazol-2 yl] carbamate (compound 81/470) in hamster against Ancylostoma ceylanicum infection, plasma level of the compound and status of reactive oxygen metabolites in jejunum at different periods of the drug treatment were examined. The compound was found to enhance the generation of both O2- and H2O2 by the jejunum possibly by activating xanthine oxidase. This stimulation was found to be both time and dose dependent. At 100 mg/kg dose the increase in O2- production could be recorded at least upto 50 days, whereas at 25 mg/kg the stimulation remained effective upto 20 days only, and at 5 mg/kg there was no change in the activity. This correlated well with the reported prophylactic pattern of the compound i.e. upto 45 and 7 days by 100 and 25 mg/kg doses, respectively. Plasma level of the compound also exhibited dose dependent variation. The compound given at 100 mg/kg dose could be detected in significant concentration upto at least 42 days while that given in 25 and 5 mg/kg doses was present in equivalent concentration upto 14 days and 1 day, respectively. It is concluded that the activation of respiratory burst in the jejunum induced by the persistent presence of compound 81/470 may represent one of the important mechanisms for the chemoprophylactic activity of this anthelmintic.
Division of Biochemistry, Central Drug Research Institute, Lucknow, India.
S P
SP
Singh
J K
JK
Srivastava
J C
JC
Katiyar
V M
VM
Srivastava
D000722:Ancylostoma / Q000187:drug effects*; D000724:Ancylostomiasis / Q000517:prevention & control; D000818:Animals; D000923:Anticestodal Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002219:Carbamates / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D007583:Jejunum / Q000201:enzymology / Q000469:parasitology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D000923:Anticestodal Agents; D001562:Benzimidazoles; D002219:Carbamates; D017382:Reactive Oxygen Species; D013481:Superoxides; C043589:CDRI 81-470; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase