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Research
(Published
online: 16-07-2014)
9. Subacute toxicopathological studies of
methotrexate in Wistar rats - N. N. Patel, D. J.
Ghodasara, Sunanda Pandey, Priya D. Ghodasara, J. H. Khorajiya, B.
P. Joshi and C. J. Dave
Veterinary World, 7(7): 489-495
doi:
10.14202/vetworld.2014.489-495
N. N.
Patel:
Department of Veterinary Pathology, College of Veterinary Science
and Animal Husbandry, Anand Agricultural University, Anand,
Gujarat - 388001, India; nupur1989@gmail.com
D. J.
Ghodasara:
Department of Veterinary Pathology, College of Veterinary Science
and Animal Husbandry, Anand Agricultural University, Anand,
Gujarat - 388001, India; dinghodasara@gmail.com
Sunanda
Pandey:
Department of Veterinary Pathology, College of Veterinary Science
and Animal Husbandry, Anand Agricultural University, Anand,
Gujarat - 388001, India; drsunandapandey@gmail.com
Priya D. Ghodasara:
Department of Veterinary Pathology, College of Veterinary Science
and Animal Husbandry, Anand Agricultural University, Anand,
Gujarat - 388001, India; priyaghodasara@yahoo.com
J. H. Khorajiya:
Department of Veterinary Pathology, College of Veterinary Science
and Animal Husbandry, Anand Agricultural University, Anand,
Gujarat - 388001, India; jainudeen_1990@rediffmail.com
B. P. Joshi:
Department of Veterinary Pathology, College of Veterinary Science
and Animal Husbandry, Anand Agricultural University, Anand,
Gujarat - 388001, India; b4bpjoshi@gmail.com
C. J. Dave:
Department of Veterinary Pathology, College of Veterinary Science
and Animal Husbandry, Anand Agricultural University, Anand,
Gujarat - 388001, India; c4cjdave@gmail.com
Received: 11-04-2014, Revised: 07-06-2014, Accepted: 11-06-2014,
Published online: 16-07-2014
Corresponding author: D. J. Ghodasara, email:
dinghodasara@gmail.com
Abstract
Aim: A toxico-pathological
study was undertaken to assess the effects of Methotrexate
administration in Wistar rats by performing the hematology, serum
biochemical analysis and associated histopathological changes in
visceral organs.
Materials and Methods: Rats in 4 treatment groups with 6
male and 6 female rats each were administered methotrexate (Group
II to IV) at the dose rate of 0.062, 0.125 and 0.250 mg/kg body
weight respectively and distilled water (Group I) as vehicle
control for 28 days. Hematological parameters viz., total
erythrocyte count, haemoglobin, packed cell volume, MCV, MCH and
MCHC, total leukocyte count and differential leukocyte count and
serum biochemical parameters viz., aspartate aminotransferase,
alanine aminotransferase, alkaline phosphatase, serum creatinine,
blood urea nitrogen, total protein, albumin, globulin (Calculated)
were estimated after 28 days. Necropsy examination was performed
in all sacrificed animals and gross lesions were recorded. Tissue
samples (lung, liver, kidney, intestine, testes and heart) were
collected in 10% formalin solution for histo-pathological
examination.
Results: The dose dependent reduction in body weight, feed
consumption, RBCs count, packed cell volume, haemoglobin, total
leucocyte count, neutrophil count, total protein and albumin was
observed in animals of group II, III and IV along with significant
increase in lymphocyte count, AST, ALT, AKP, creatinine and BUN in
animals of methotrexate treated group IV followed by group III. No
significant change in monocyte, eosinophil and basophil counts
were observed in any treatment groups. All the rats exposed to
methotrexate at three different dose levels revealed dose
dependent pathological changes characterized by degeneration,
necrosis, congestion, haemorrhage and vascular changes. The main
target organs affected were liver, kidney, lungs and testes.
Conclusion: It can be concluded from this study that
sub-acute exposure to methotrexate produced no appreciable changes
at recommended 0.062 mg/kg body weight dose level. The findings
observed at 0.250 mg/kg body weight methotrexate dose level are of
public health significance and regulatory importance due to its
hepatotoxic and nephrotoxic character.
Keywords: biochemical parameters, histopathology,
methotrexate, Wistar rats.
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