Efficacy of oryzalin and associated histological changes in Cryptosporidium-infected neonatal rats.
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.
Armson
A
A
Centre for Biomolecular Control of Disease, Western Australian Biomedical Research Institute, Murdoch University, Perth. armson@numbat.murdoch.edu.au
Menon
K
K
O'Hara
A
A
MacDonald
L M
LM
Read
C M
CM
Sargent
K
K
Thompson
R C A
RC
Reynoldson
J A
JA
D000818:Animals; D000831:Animals, Newborn; D002851:Chromatography, High Pressure Liquid; D003049:Coccidiostats / Q000494:pharmacology / Q000627:therapeutic use*; D003457:Cryptosporidiosis / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology*; D016785:Cryptosporidium parvum / Q000187:drug effects / Q000502:physiology*; D004136:Dinitrobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007422:Intestines / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D033661:Oocysts / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013424:Sulfanilamides; D013997:Time Factors
D003049:Coccidiostats; D004136:Dinitrobenzenes; D013424:Sulfanilamides; C012465:oryzalin