Evaluation of Nephro, Hepato and Gastro toxic potential of aqueous ...
Evaluation of Nephro, Hepato and Gastro toxic potential of aqueous ...
Evaluation of Nephro, Hepato and Gastro toxic potential of aqueous ...
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International Journal <strong>of</strong> Research in Pharmaceutical <strong>and</strong> Biomedical Sciences ISSN: 2229-3701____________________________________________Research Paper<strong>Evaluation</strong> <strong>of</strong> <strong>Nephro</strong>, <strong>Hepato</strong> <strong>and</strong> <strong>Gastro</strong> <strong>toxic</strong> <strong>potential</strong> <strong>of</strong><strong>aqueous</strong> extract <strong>of</strong> DashamulaDawane JS 1* , Borole KD 1 , P<strong>and</strong>it VA 1 , Dhrubajyoti Dey 1 , Sahane SS 1 <strong>and</strong> Kar<strong>and</strong>ikar MN 21Department <strong>of</strong> Pharmacology, Bharati Vidyapeeth Deemed University Medical College,Pune, Maharashtra, India.2Department <strong>of</strong> Pathology, Bharati Vidyapeeth Deemed University Medical College, Pune,Maharashtra, India._____________________________________________________________________________________ABSTRACTAqueous extract <strong>of</strong> Dushamula, a polyherbal preparation, made up <strong>of</strong> ten roots, is used routinely to treat pain,swelling & fever by Vaidyas. The main objective is to study the effect <strong>of</strong> Aqueous Extract <strong>of</strong> Dashamula on kidney,liver <strong>and</strong> stomach <strong>and</strong> to compare it with Dicl<strong>of</strong>enac sodium. For this study, 18 albino rats were divided into threegroups; Gr. I vehicle(Water), Gr. II Aqueous Extract <strong>of</strong> Dashamula (2.90 ml/200gms) <strong>and</strong> Gr.III St<strong>and</strong>ard drugDicl<strong>of</strong>enac sodium (2.90 mg/200gms) orally for 14 days. On day-15 blood samples were collected for liver & kidneyfunction tests. All animals were then sacrificed & kidney, liver <strong>and</strong> stomach were removed for histopathology.Liver function test (AST & ALT, Bilirubin) values were significantly (P< 0.001) increased in Dicl<strong>of</strong>enac treated groupas compared to control & Dashamula group. Compared to the control group, total bilirubin was significantly (P
International Journal <strong>of</strong> Research in Pharmaceutical <strong>and</strong> Biomedical Sciences ISSN: 2229-3701sinusoids <strong>and</strong> endothelium. This enzyme reaches theliver mainly from the bone. It is excreted into thebile; therefore its elevation in serum occurs inhepatobiliary diseases. 25 Though there was slightincrease in ALP levels in Dashamula <strong>and</strong> Dicl<strong>of</strong>enacsodium group, it was not significant <strong>and</strong> these valueswere comparable in all the groups.The reduction in the total protein is attributed to theinitial damage produced <strong>and</strong> localized in theendoplasmic reticulum which results in the loss <strong>of</strong>cytochrome P-450 enzymes leading to its functionalfailure with a decrease in protein synthesis <strong>and</strong>accumulation <strong>of</strong> triglycerides leading to fatty liver . [26]In our results (Table-2) though there was decrease inthe Total Protein levels in both the drug treatedgroups, decrease in Dicl<strong>of</strong>enac group was significant.Serum Albumin is the major plasma proteinsynthesized in human liver <strong>and</strong> is the importantmarker <strong>of</strong> hepatic synthetic function. Albumin levelswere highly significantly reduced in Dicl<strong>of</strong>enacgroup.Total Bilirubin concentration indicates the functionaltransport capacity as well as conjugating ability <strong>of</strong>liver. Total Bilirubin in Dicl<strong>of</strong>enac treated group wassignificantly high. The values <strong>of</strong> Direct Bilirubinwere comparable in all the groups suggesting nochange in the conjugating ability <strong>of</strong> liver.In Dashamula treated group, the values obtained forliver function parameters showed that the conjugating<strong>and</strong> the synthetic abilities <strong>of</strong> the liver were notcompromised from the total <strong>and</strong> conjugating bilirubinlevels <strong>and</strong> also from Albumin <strong>and</strong> Total Proteinlevels [Table-2]. There was no hepatocellular damageas revealed by the ALT <strong>and</strong> AST values.Dicl<strong>of</strong>enac TreatedDicl<strong>of</strong>enac TreatedTubular epithelial damage with intensegranular denegeration.Glomerularcongestion,inflammatiory cells,necrosis<strong>and</strong> tubular castsFig. 1: Effect <strong>of</strong> <strong>aqueous</strong> extract <strong>of</strong> Dashamula<strong>and</strong> Dicl<strong>of</strong>enac on Kidney histopathologyControlDashamula TreatedControlDicl<strong>of</strong>enac TreatedDashamula TreatedFig. 2: Effect <strong>of</strong> <strong>aqueous</strong> extract <strong>of</strong> Dashamula<strong>and</strong> Dicl<strong>of</strong>enac on liver histopathologyVol. 3 (1) Jan – Mar 2012 www.ijrpbsonline.com 16
International Journal <strong>of</strong> Research in Pharmaceutical <strong>and</strong> Biomedical Sciences ISSN: 2229-3701These findings were supported by histopathologyresults. <strong>Hepato</strong>cyte necrosis, mild fibrous tissueproliferation <strong>and</strong> interstitial <strong>and</strong> periportalinflammation indicate acute hepatitis. These findingssuggest that Dicl<strong>of</strong>enac sodium causes irreversiblecell death as well as cell damage, fibrousproliferation <strong>and</strong> acute hepatitis. Dilatation <strong>of</strong> thecentral vein, sinusoidal dilatation around the centralvein, bile duct proliferation was prominent inDicl<strong>of</strong>enac group. Enlargement <strong>of</strong> some portal areas<strong>and</strong> cloudy swelling with parenchymal cell necrosiswas also noticed. These changes were absent inDashamula treated <strong>and</strong> Control group.Dicl<strong>of</strong>enac causes gastirc irritation because <strong>of</strong>inhibition <strong>of</strong> cyclooxygenase enzyme <strong>and</strong> in turnProstagl<strong>and</strong>in synthesis consequently reduces mucusproduction. Thus ultemately the protective effect <strong>of</strong>Prostagl<strong>and</strong>ins on gastric mucosa is lost. Long termuse <strong>of</strong> NSAIDs is associated with severe gastropathythat may arise from induction <strong>of</strong> gastric mucosal cell[28]apoptosis. Sum <strong>of</strong> total <strong>of</strong> ulcer Indices <strong>of</strong>Dicl<strong>of</strong>enac group was statistically significantlyhigher than control <strong>and</strong> Dashamula treated groups.These findings confirm that Dashamula is less irritantto gastric mucosa than Dicl<strong>of</strong>enac.Thus, Dashamula a polyherbal preparation appears tohave definitely low adverse effect pr<strong>of</strong>ile in terms <strong>of</strong><strong>Nephro</strong>, <strong>Hepato</strong> <strong>and</strong> Gastric <strong>toxic</strong>ity when comparedwith the st<strong>and</strong>ard anti-inflammatory, analgesic drugDicl<strong>of</strong>enac sodium.Table 1: Effect <strong>of</strong> <strong>aqueous</strong> extract <strong>of</strong> Dashamula <strong>and</strong>Dicl<strong>of</strong>enac on Renal Function TestsParameters Group I- Control Group II-Dashamula Group III-Dicl<strong>of</strong>enacUrea 34.8 ± 3.12 29.8 ± 2.81 46.02 ± 5.53** ¥Creatinine 0.86 ± 0.03 0.79 ± 0.02 0.94 ± 0.09n= 6,The observations are mean±SEM,*P
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