Objective—To determine essential fatty acid concentrations
in plasma and tissue before and after supplementation
with n-3 fatty acids in dogs with atopic dermatitis.
Animals—30 dogs with atopic dermatitis.
Procedure—Dogs received supplemental flaxseed oil
(200 mg/kg/d), eicosapentaenoic acid (EPA;
50 mg/kg/d)-docosahexaenoic acid (DHA;
35 mg/kg/d), or mineral oil as a placebo in a doubleblind,
placebo-controlled, randomized trial. Clinical
scores and plasma and cutaneous concentrations of
linoleic acid, arachidonic acid, α-linolenic acid (α-LLA),
EPA, DHA, prostaglandin E2, and leukotriene B4 were
Results—Total plasma concentrations of α-LLA and
EPA increased and those of arachidonic acid
decreased significantly with administration of EPADHA,
and concentrations of α-LLA increased with
flaxseed oil supplementation; nevertheless, there
was no significant change in the concentrations of
these fatty acids or eicosanoids in the skin. There was
no correlation between clinical scores and plasma or
cutaneous concentrations for any of the measured
fatty acids or eicosanoids.
Conclusion and Clinical Relevance—Results indicated
that at the dose used, neither the concentrations
of fatty acids in skin or plasma nor a decrease in
the production of inflammatory eicosanoids was a
major factor involved in the mechanism of action in
dogs with atopy that responded to fatty acid supplementation.
(Am J Vet Res 2005;66:868–873)
Objective—To identify matrix metalloproteinases
(MMP) 2 and 9 in canine tumor tissue and to compare
the amount of activity to that in unaffected stromal
Animals—30 dogs with spontaneously developing,
Procedure—Tumor and nearby stromal tissue (muscle)
were obtained at the time of surgery. Specimens were
homogenized, and supernatants were assayed, using
gelatin zymography. Human derived standards were
run concurrently. Densitometry was done to obtain a
semiquantitative arbitrary unit value for each specimen.
The amount of activity in tumor tissue was compared
with the amount in stromal tissue.
Results—Gelatinolytic bands were observed from
the analysis of all tumor tissues and in most stromal
tissues. These bands migrated in the same molecular
weight area as the human MMP 2 and 9 standards.
Gelatinolytic activity could be quenched by the addition
of 50 mM EDTA and 1 µg of synthetic tissue
inhibitor of metalloproteinase (TIMP) 2 per 100 ml.
There was significantly more gelatinolytic activity in
tumor tissue than in stromal tissue.
Conclusions and Clinical Relevance—MMP 2 and 9
are detectable in canine neoplastic tissue. matrix metalloproteinases
activity in tumor tissue is higher than in
unaffected stromal tissue, indicating that canine MMP
may be involved in the pathogenesis of tumor growth
and metastasis. (Am J Vet Res 2000;61:111–114)
Objective—To determine the effect of dietary n-3 fatty acids on the pharmacokinetics of doxorubicin in dogs with lymphoma.
Animals—23 dogs with lymphoma in stages IIIa, IVa, and Va.
Procedure—Dogs receiving doxorubicin chemotherapy were randomly allocated to receive food with a high (test group) or low (control group) content of n-3 fatty acids. Serum doxorubicin and doxorubicinol concentrations were measured via high-performance liquid chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node concentrations of doxorubicin were assessed 6 hours after the initial treatment. Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry scans.
Results—No significant differences in doxorubicin pharmacokinetics were detected between treatment groups. Significant differences existed between the first and second sampling times among all dogs for area under the curve, maximum serum concentration, and clearance. Differences in body composition did not affect measured pharmacokinetic variables. The terminal elimination half-life was longer in dogs in which a long-term remission was achieved than in dogs that did not have remission.
Conclusions and Clinical Relevance—Dietary supplementation of n-3 fatty acids is common in veterinary patients with neoplasia, but supplementation did not affect doxorubicin pharmacokinetics in this population of dogs. Explanations for the beneficial effects of n-3 fatty acids other than alterations in the pharmacokinetics of chemotherapy drugs should be investigated. Dogs may metabolize drugs differently prior to remission of lymphoma than when in remission. The pharmacokinetics of doxorubicin at the time of the first administration may predict response to treatment.