Please use this identifier to cite or link to this item: http://krishikosh.egranth.ac.in/handle/1/5810086691
Authors: SHWETHA REDDY R. V
Advisor: Dr. A. GOPALA REDDY
Title: HEPATOPROTECTIVE POTENTIAL OF COSTUS PICTUS AGAINST EXPERIMENTAL HEPATOTOXICITY WITH SPECIAL REFERENCE TO CYP3A4 FUNCTIONING IN RATS
Publisher: PVNR TVU
Language: en
Type: Thesis
Pages: 142
Agrotags: null
Abstract: The safety pharmacology of Costus pictus was studied (shade dried leaf aqueous extract) by using different doses (250, 500, 750 and 1000 mg/kg b. wt. once daily orally) in rats. A total of 30 adult Sprague dawley rats were divided into 5 groups (viz., 1, 2, 3, 4 and 5) of 6 rats in each (one control group and the remaining 4 groups were treated with Costus pictus aqueous extract with the above doses for 14 days). Lipid profile (total cholesterol, HDL cholesterol and triglycerides) was done with the plasma samples, rats were euthanized on day 15 after blood collection, liver heart and kidney tissues were collected for histopathology and homogenized for the assay of TBARS and GSH. BUN, creatinine and glucose were significantly altered and histopathological studies revealed no changes in heart, mild tubular inflammation and tubular degeneration in groups 2, 3, 4 and 5 of kidney, and mild infiltration of inflammatory cells in group 4 and 5 of liver in safety pharmacology. In hepatoprotective study, the therapeutic efficacy and antioxidant potential of N-Acetyl cysteine and Costus pictus (aqueous extract of dried leaves) were studied against acetaminophen (APAP) @ 500 mg/kg BW-induced hepatotoxicity. A total of 24 male Sprague dawley rats of 3 months age were randomly divided into four groups, consisting of 6 in each group. Acetaminophen @ 500 mg/kg BW was administered orally to all the groups from day 1 to 3. Group 1 was maintained as normal control. Group 2 was subsequently administered with distilled water (p/o) from day 4 to 17 and was considered as toxic control. Groups 3 and 4 were administered (p/o) with N-Acetyl cysteine @ 300 mg/kg BW and Costus pictus extract @ 500 mg/kg BW, respectively from day 4 to 17. In hepatoprotective study biomarker of hepatotoxicity (ALT) was estimated on day 4 (confirmation of toxicity) and 18 (at the end of treatment). Antioxidant profiles (TBARS, GSH, SOD, GPx and catalase) and enzymes like ATPases were assessed at the end of experiment. Liver tissues were subjected to histopathology and transmission electron microscopy (TEM) after sacrifice on day 18. The antioxidant profile, ATPases and serobiochemical parameters were significantly altered and histopathological studies revealed necrosis of hepatocytes around central vein, sinusoidal dilation, vacuolar degeneration and infiltration were noticed in liver of toxic control group 2. These changes were reversed in groups 3 and 4 that were administered with N-Acetyl cysteine and Costus pictus extract, respectively. In order to evaluate the functioning of CYP3A4, 20 Sprague dawley rats of 3 months age were divided into 4 groups, comprising of 5 rats in each for pharmacokinetics of atorvastatin, specific substrate for CYP3A4 and these groups were maintained as per the above schedule mentioned under hepatoprotective study. Atorvastatin was administered on day 18 as single oral dose in all the groups and blood samples were drawn at specified intervals for pharmacokinetic analysis. Atorvastatin metabolism was altered in APAP treated toxic group, which was reflected in increase in Cmax, AUC0-t, AUMC0-t, AUC0-∞ and AUMC0-∞ that eventually resulted in prolonged t1/2β, MRT and decrease in clearance. Among the treated groups, group 3 (NAC) revealed better metabolic profile of CYP3A4 as compared to group 4 (Costus pictus extract). In conclusion, the results of the safety pharmacology proved the safety of Costus pictus apart from its hypoglycemic property and mild renal toxicity. The results of the present hepatoprotective investigation enunciated that Costus pictus has potent hepatoprotective activity, though the N-acetyl-L-cysteine was found superior based on pharmacodynamics and pharmacokinetic parameters in this study. The overall beneficial effects of Costus pictus extract are attributed to the antioxidant potential as evident from oxidant-antioxidant markers in this study coupled to hepatoprotective property.
Subject: Veterinary Pharmacology and Toxicology
Theme: VPT
These Type: M.V.Sc.
Issue Date: 2017-12-01
Appears in Collections:Thesis

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