Pathomorphological, Biochemical and Molecular Evaluation of Methotrexate Induced Hepato-Toxicity and its Amelioration by Tinospora Cordifolia
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Date
2014-09-29
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Karnataka Veterinary, Animal and Fisheries Sciences University, Bidar
Abstract
The present study was taken up to evaluate the pathomorphological, biochemical
and molecular changes in methotrexate induced hepatotoxicity and it’s amelioration by
Tinospora cordifolia in rats for 45 days. The various groups in this study included normal
control (Group-I), methotrexate control (Group-II), rats treated with Tinospora cordifolia
concurrently with administration of methotrexate (Group-III), rats treated with
Tinospora cordifolia ten days prior to and following administration of methotrexate
(Group-IV), Tinospora cordifolia control (Group-V) respectively. Hepatotoxicity was
induced in rats by administration of methotrexate at the dose of 5mg/kg body weight for
three consecutive days and the aqueous extract of Tinospora cordifolia was used at a dose
rate of 200mg /kg body weight. Pathomorphological, biochemical and molecular
changes following methotrexate administration and Tinospora cordifolia treatment in
different groups were assessed by the measurement of various hematological parameters,
biochemical enzymes, antioxidants and lipid peroxidation assay, histopathology,
Annexin-V and Sytox green staining for detection of apoptotic cells, DNA fragmentation
assay, Immunohistochemical evaluation of p53 expression in liver and by relative
quantification of P53 expression in liver by realtime PCR. Methotrexate induced
hepatotoxicity was characterized by both necrosis and apoptosis. The concurrent and
pretreatment with Tinospora cordifolia alleviated the methotrexate induced hepatotoxic
effects. The pretreatment of Tinospora cordifolia showed a prophylactic effect. In
addition the study also showed that Tinospora cordifolia has antiapoptotic effect and
alleviated methotrexate induced apoptosis.
Description
Ph.D. Thesis