Hepatic disposition of neurotoxins and pesticides.
The hepatic disposition of pesticides and neurotoxins may influence susceptibility to Parkinson's disease. Therefore we examined the behaviour of paraquat, dichlorodiphenyltrichloroethane (DDT), malathion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in perfused rat liver using the multiple indicator-dilution technique. The values for the recovery of paraquat, DDT, malathion and MPTP were 1.05+/-0.12, 0.32+/-0.01, 0.11+/-0.02 and 0.02+/-0.01, respectively. The volumes of distribution were 0.28+/-0.13, 0.69+/-0.12, 3.30+/-0.58 and 5.10+/-6.00 ml/g, respectively. The permeability-surface area products suggest that transport of DDT and MPTP across cell membranes is by simple diffusion. However, there may be a specific influx mechanism for malathion and a specific efflux mechanism for paraquat. There is considerable variability in the hepatic disposition of putative neurotoxins such as MPTP and pesticides. Factors that influence the hepatic disposition of neurotoxins may alter susceptibility to neurotoxic diseases however the effects will be diverse.
Yang
M C
MC
Canberra Clinical School of the University of Sydney, The Canberra Hospital, Garran, ACT, Australia. Maria.Yang@anu.edu.au
McLean
A J
AJ
Rivory
L P
LP
Le Couteur
D G
DG
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003634:DDT / Q000493:pharmacokinetics; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008294:Malathion / Q000493:pharmacokinetics; D008297:Male; D009498:Neurotoxins / Q000493:pharmacokinetics*; D010269:Paraquat / Q000493:pharmacokinetics; D010300:Parkinson Disease / Q000378:metabolism; D010477:Perfusion; D010575:Pesticides / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D009498:Neurotoxins; D010575:Pesticides; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003634:DDT; D010269:Paraquat; D008294:Malathion