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Efficacy of oryzalin and associated histological changes in Cryptosporidium-infected neonatal rats

Published online by Cambridge University Press:  16 January 2003

A. ARMSON ,
K. MENON ,
A. O'HARA ,
L. M. MACDONALD ,
C. M. READ ,
K. SARGENT ,
R. C. A. THOMPSON  and
J. A. REYNOLDSON
A. ARMSON
Affiliation:
Centre for Biomolecular Control of Disease, Western Australian Biomedical Research Institute and Division of Veterinary and Biomedical Sciences, Murdoch University, Perth 6150, Australia
K. MENON
Affiliation:
Centre for Biomolecular Control of Disease, Western Australian Biomedical Research Institute and Division of Veterinary and Biomedical Sciences, Murdoch University, Perth 6150, Australia
A. O'HARA
Affiliation:
Centre for Biomolecular Control of Disease, Western Australian Biomedical Research Institute and Division of Veterinary and Biomedical Sciences, Murdoch University, Perth 6150, Australia
L. M. MACDONALD
Affiliation:
Centre for Biomolecular Control of Disease, Western Australian Biomedical Research Institute and Division of Veterinary and Biomedical Sciences, Murdoch University, Perth 6150, Australia
C. M. READ
Affiliation:
Centre for Biomolecular Control of Disease, Western Australian Biomedical Research Institute and Division of Veterinary and Biomedical Sciences, Murdoch University, Perth 6150, Australia
K. SARGENT
Affiliation:
Centre for Biomolecular Control of Disease, Western Australian Biomedical Research Institute and Division of Veterinary and Biomedical Sciences, Murdoch University, Perth 6150, Australia
R. C. A. THOMPSON
Affiliation:
Centre for Biomolecular Control of Disease, Western Australian Biomedical Research Institute and Division of Veterinary and Biomedical Sciences, Murdoch University, Perth 6150, Australia
J. A. REYNOLDSON
Affiliation:
Centre for Biomolecular Control of Disease, Western Australian Biomedical Research Institute and Division of Veterinary and Biomedical Sciences, Murdoch University, Perth 6150, Australia
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Abstract

This paper reports the anti-cryptosporidial effects of, and concomitant amelioration of the histological changes in the gut of neonatal rats with intestinal cryptosporidiosis treated with the dinitroaniline, oryzalin. The ED50 was determined to be 7 mg/kg using twice daily doses administered for 3 consecutive days. A maximum inhibition of 85.5% was achieved at 25 mg/kg and this inhibition remained constant despite increasing the oryzalin dose to 200 mg/kg. Cryptosporidiosis significantly decreased the intestinal villus/crypt (VC) ratio by approximately 50% (duodenum = 2.3, jejunum = 2.5 and ileum = 1.7) when compared to uninfected untreated controls (duodenum = 4.3, jejunum = 5.9 and ileum = 4.5). Treatment with oryzalin doubled the VC ratio in the duodenum, jejunum and ileum following doses of 5 mg, 50 mg and 200 mg/kg respectively. Oryzalin concentrations in the small intestine contents and plasma were determined, using HPLC, at 0.5, 1 and 2 h after dosing. The much greater dose required to return VC ratios to normal in the ileum (200 mg/kg) compared to the duodenum (6.25 mg/kg) appeared to reflect the decreased concentration of the drug in the distal small intestine. Concentrations of oryzalin equivalent to the in vitro IC50 were maintained for 2 h in the first half of the small intestine following a single dose of 100 mg/kg.

Keywords

Cryptosporidiumvillus/cryptdinitroanilineoryzalincoccidiosis
Type
Original Article
Information
Parasitology , Volume 125 , Issue 2 , August 2002 , pp. 113 - 117
Copyright
2002 Cambridge University Press

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