Dimethylnitrosamine-induced hepatotoxicosis in dogs as a model of progressive canine hepatic disease

D. M. Boothe From the Departments of Veterinary Physiology and Pharmacology (D. M. Boothe, Weise), Veterinary Pathology (Green), Small Animal Medicine and Surgery (H. W. Boothe), The Texas Veterinary Medical Center, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466; Office of the Dean Jenkins), School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803; USDA, ARS, VTERL (Corrier), College Station, TX 77843; and Department of Microbiology, Pathology and Parasitology (Cullen), College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

Search for other papers by D. M. Boothe in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
W. L. Jenkins From the Departments of Veterinary Physiology and Pharmacology (D. M. Boothe, Weise), Veterinary Pathology (Green), Small Animal Medicine and Surgery (H. W. Boothe), The Texas Veterinary Medical Center, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466; Office of the Dean Jenkins), School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803; USDA, ARS, VTERL (Corrier), College Station, TX 77843; and Department of Microbiology, Pathology and Parasitology (Cullen), College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

Search for other papers by W. L. Jenkins in
Current site
Google Scholar
PubMed
Close
 BVSc, MMedVet, PhD
,
R. A. Green From the Departments of Veterinary Physiology and Pharmacology (D. M. Boothe, Weise), Veterinary Pathology (Green), Small Animal Medicine and Surgery (H. W. Boothe), The Texas Veterinary Medical Center, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466; Office of the Dean Jenkins), School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803; USDA, ARS, VTERL (Corrier), College Station, TX 77843; and Department of Microbiology, Pathology and Parasitology (Cullen), College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

Search for other papers by R. A. Green in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
D. E. Corrier From the Departments of Veterinary Physiology and Pharmacology (D. M. Boothe, Weise), Veterinary Pathology (Green), Small Animal Medicine and Surgery (H. W. Boothe), The Texas Veterinary Medical Center, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466; Office of the Dean Jenkins), School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803; USDA, ARS, VTERL (Corrier), College Station, TX 77843; and Department of Microbiology, Pathology and Parasitology (Cullen), College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

Search for other papers by D. E. Corrier in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
J. M. Cullen From the Departments of Veterinary Physiology and Pharmacology (D. M. Boothe, Weise), Veterinary Pathology (Green), Small Animal Medicine and Surgery (H. W. Boothe), The Texas Veterinary Medical Center, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466; Office of the Dean Jenkins), School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803; USDA, ARS, VTERL (Corrier), College Station, TX 77843; and Department of Microbiology, Pathology and Parasitology (Cullen), College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

Search for other papers by J. M. Cullen in
Current site
Google Scholar
PubMed
Close
 VMD, PhD
,
H. W. Boothe From the Departments of Veterinary Physiology and Pharmacology (D. M. Boothe, Weise), Veterinary Pathology (Green), Small Animal Medicine and Surgery (H. W. Boothe), The Texas Veterinary Medical Center, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466; Office of the Dean Jenkins), School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803; USDA, ARS, VTERL (Corrier), College Station, TX 77843; and Department of Microbiology, Pathology and Parasitology (Cullen), College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

Search for other papers by H. W. Boothe in
Current site
Google Scholar
PubMed
Close
 DVM, MS
, and
D. Weise From the Departments of Veterinary Physiology and Pharmacology (D. M. Boothe, Weise), Veterinary Pathology (Green), Small Animal Medicine and Surgery (H. W. Boothe), The Texas Veterinary Medical Center, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466; Office of the Dean Jenkins), School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803; USDA, ARS, VTERL (Corrier), College Station, TX 77843; and Department of Microbiology, Pathology and Parasitology (Cullen), College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

Search for other papers by D. Weise in
Current site
Google Scholar
PubMed
Close
 BS

Click on author name to view affiliation information

Summary

A model of toxin-induced progressive hepatitis is described in Beagles. The toxin, dimethylnitrosamine, was administered orally to 18 Beagles; 6 dogs comprised a control group. Clinical signs and laboratory test results were monitored as disease progressed and were used to determine the end point of disease. Following euthanasia, histologic lesions were scored and used to derive a total severity score for each dog. Severity scores were then used to allot the 18 dogs to 3 groups of hepatic disease, defined as mild, moderate, or severe. Changes in clinical laboratory test results, including tests of hepatic function, and clinical signs indicative of liver disease were described chronologically for all dogs. Group means of clinical laboratory test results and quantifiable clinical signs (eg, weight loss and ascitic fluid accumulation) were compared. This model offers several advantages, compared with other experimental models of canine hepatic disease. These include hepatospecificity, similarity to natural disease (eg, the development of multiple extrahepatic portosystemic shunts), and the ability to titrate the disease to a desired end point. The major disadvantages of this model were the toxic nature of the drug to human beings and the variation in individual animal response to the toxin, which precludes preassignment of animals into groups.

Summary

A model of toxin-induced progressive hepatitis is described in Beagles. The toxin, dimethylnitrosamine, was administered orally to 18 Beagles; 6 dogs comprised a control group. Clinical signs and laboratory test results were monitored as disease progressed and were used to determine the end point of disease. Following euthanasia, histologic lesions were scored and used to derive a total severity score for each dog. Severity scores were then used to allot the 18 dogs to 3 groups of hepatic disease, defined as mild, moderate, or severe. Changes in clinical laboratory test results, including tests of hepatic function, and clinical signs indicative of liver disease were described chronologically for all dogs. Group means of clinical laboratory test results and quantifiable clinical signs (eg, weight loss and ascitic fluid accumulation) were compared. This model offers several advantages, compared with other experimental models of canine hepatic disease. These include hepatospecificity, similarity to natural disease (eg, the development of multiple extrahepatic portosystemic shunts), and the ability to titrate the disease to a desired end point. The major disadvantages of this model were the toxic nature of the drug to human beings and the variation in individual animal response to the toxin, which precludes preassignment of animals into groups.

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 58 58 23
PDF Downloads 26 26 7
Advertisement