Host genetic influences on the anthelmintic efficacy of papaya-derived cysteine proteinases in mice.
Eight strains of mice, of contrasting genotypes, infected with Heligmosomoides bakeri were studied to determine whether the anthelmintic efficacy of papaya latex varied between inbred mouse strains and therefore whether there is an underlying genetic influence on the effectiveness of removing the intestinal nematode. Infected mice were treated with 330 nmol of crude papaya latex or with 240 nmol of papaya latex supernatant (PLS). Wide variation of response between different mouse strains was detected. Treatment was most effective in C3H (90·5-99·3% reduction in worm counts) and least effective in CD1 and BALB/c strains (36·0 and 40·5%, respectively). Cimetidine treatment did not improve anthelmintic efficacy of PLS in a poor drug responder mouse strain. Trypsin activity, pH and PLS activity did not differ significantly along the length of the gastro-intestinal (GI) tract between poor (BALB/c) and high (C3H) drug responder mouse strains. Our data indicate that there is a genetic component explaining between-mouse variation in the efficacy of a standard dose of PLS in removing worms, and therefore warrant some caution in developing this therapy for wider scale use in the livestock industry, and even in human medicine.
School of Life Sciences,University of Nottingham,University Park,Nottingham,NG7 2RD,UK.
Wenceslaus
W
Luoga
School of Life Sciences,University of Nottingham,University Park,Nottingham,NG7 2RD,UK.
Fadlul
F
Mansur
School of Life Sciences,University of Nottingham,University Park,Nottingham,NG7 2RD,UK.
Gillian
G
Stepek
School of Life Sciences,University of Nottingham,University Park,Nottingham,NG7 2RD,UK.
Ann
A
Lowe
School of Life Sciences,University of Nottingham,University Park,Nottingham,NG7 2RD,UK.
Ian R
IR
Duce
Department of Infection and Immunity,University of Sheffield Medical School,Beech Hill Road,Sheffield S10 2RX,UK.
David J
DJ
Buttle
School of Life Sciences,University of Nottingham,University Park,Nottingham,NG7 2RD,UK.
Jerzy M
JM
Behnke
D000818:Animals; D000871:Anthelmintics / Q000378:metabolism / Q000494:pharmacology*; D029441:Carica / Q000737:chemistry* / Q000201:enzymology; D002927:Cimetidine / Q000494:pharmacology; D057056:Cysteine Proteases / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000469:parasitology; D005838:Genotype; D058507:Host Specificity; D006863:Hydrogen-Ion Concentration; D007840:Latex / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017184:Nematospiroides / Q000187:drug effects / Q000502:physiology; D010940:Plant Proteins / Q000378:metabolism / Q000494:pharmacology*; D012376:Rodent Diseases / Q000188:drug therapy / Q000235:genetics* / Q000469:parasitology; D013045:Species Specificity; D017206:Strongylida Infections / Q000188:drug therapy / Q000235:genetics* / Q000469:parasitology
D000871:Anthelmintics; D007840:Latex; D010940:Plant Proteins; D002927:Cimetidine; D057056:Cysteine Proteases
Heligmosomoides bakeri; anthelmintics; cysteine proteinases; genetics; nematodes; papaya latex