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Subject: Veterinary Pathology × Author: ARUNDHATHI, S × Start date: 2008 × Thesis Type: M.V.Sc. ×
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    ThesisItemOpen Access
    PATHOLOGICAL STUDIES OF EXPERIMENTALLY INDUCED COMBINED (ISN + RIF) DRUGS TOXICITY IN RATS AND PROTECTIVE EFFECTS OF VITAMIN-E AND WITHANIA SOMNIFERA
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2008-10) ARUNDHATHI, S; ANAND KUMAR, A(MAJOR); ANJ ANEYULU, Y; GOPALA REDDY, A
    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.