PATHOLOGICAL STUDIES OF EXPERIMENTALLY INDUCED COMBINED (ISN + RIF) DRUGS TOXICITY IN RATS AND PROTECTIVE EFFECTS OF VITAMIN-E AND WITHANIA SOMNIFERA
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Date
2008-10
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SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA
Abstract
ABSTRACT:
A total of 24 healthy male Wistar rats (age 60-100 days, weighing 175-260mg)
procured for the present experimental study and the experiment was carried out according
to the guidelines and prior approval of Institutional Animal Ethics Committee. Animals
were divided into four groups consisting of 6 in each group. The experimental study was
designed as follows:- Group I-Control, Group 11-ISN@SOmg/kg body wt +
RIF@lOOmg/kg body wt once daily orally for 21 days, Group 111-ISN@SOm&g body
wt + FUF@lOOrng/kg body wt once daily orally for 21 days + Withania
sornnifira@lOOOmgkg feed daily for 21 days, Group N-ISN@SOm&g body wt +
RIF@lOOmgkg body wt once daily orally for 21 days + vitamin E@300mg/kg feed daily
for 21 days. Whole blood and serum was collected 4 times at weekly intervals (0, 7, 14
and 21 days) for estimation of various haematological and biochemical parameters and
analyzed statistically. Haematological studies revealed that overall means of PCV, Hb
and TEC were significantly (P<0.05) reduced and TLC was increased significantly
(Pc0.05) in group I1 in comparison to other groups. The biochemical assays showed a
significant (Pc0.05) reduction in total protein, HDL cholesterol, while significant
(Pc0.05) increase in AST, ALT. GGT, total cholesterol and triglycerides in group 11. The -
tissue enzyme assays revealed a significant (P<0.05) increase in TBARS and significant
(P<0.05) decrease of GSH values in group 11. The ameliorative groups 111 and IV showed
significant improvement in all parameters in comparison to group 11.
The gross pathological changes in the group I1 animals included mild
hepatomegaly. rounded borders, congestion and in heart petechiae and ecchymotic
haemomhages with focal haemorrhages on kidney. The histopathological changes in
group I1 revealed enlarged portal tracts with infiltration of lymphocytes, severe sinusoidal
congestion and fatty change in perigortal areas. Hepatocytes revealed degeneration and
moderate to severe necrosis. Heart revealed disruption and separation of muscle fibres,
endocardid haemorrhages, moderate infiltration of lymphocytes and degeneration of
muscle fibres, necrosis and fragmentation. In kidney glomeruli revealed reduction in
glomerular space, vacuolation in few glomeruli and degeneration with extensive
haemorrhages in interstitial tubular spaces, tubular epithelial cells showed fatty change
with disrupted tubules and focal areas of tubular atrophy. Brain revealed congestion,
haemorrhage and infiltration of mononuclear cells in meningeal vessels surrounding areas
fatty change and increased cellularity in granular cell layer of cerebellum. Group 111 and
IV animals revealed mild infiltration of mononuclear cells in and around portal areas with
mild sinusoidal congestion. Structural details were intact and mild fatty changes were
evident. Heart revealed mild range of degeneration and disruption of muscle bundles.
Kidney showed mild haemorrhages in interstitial spaces and normal glomerular space.
Brain revealed decreased cellularity and mild congestion in and around the meningeal
areas.
The present study concluded as follows:
I. The changes resulted by the antitubercular drugs in the haernatology can be attributed
to the hepatic damage.
2. The biochemical changes might be attributed to the toxic metabolites of the isoniazid
and rifampicin.
3. The gross and the histological changes in the study might be due to the toxic reactive
metabolites of the drugs which binds to cellular macromolecules and release or form
toxic free radicals inturn caused the tissue damage.
4. Supplementation of Withania somnifera (1%) resulted in significant improvement in
the haematological and biochemical parameters might be due to the
antioxidant, antistress, liver tonic and anti-inflammatory properties.
5. Supplementation of vitamin E (0.3%) resulted in significant improvement in
the haematological and biochemical parameters which can be attributed to the
antioxidant and anticholesterimic effects.
6. Elevation of tissue TBARS and reduction of GSH in the study might be because of
increased lipid peroxidation due to toxic reactive metabolites of the drugs.
The present study indicated that Withania somnifera @ 1OOOmgkg feed and
vitamin E @300mg/kg feed were effective in counteracting the toxic effects of the
antitubercular drugs but not up to the required levels. Keeping this in view, Wer
studies can be advocated using different dose rates and different routes of administration
to overcome the affects of antitubercular drugs which would be beneficial for
conservation of rare species on the earth.
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