Evaluation of selected parameters of rat liver injury following repeated administration of oseltamivir for different periods
Main Article Content
Abstract
The effects of oseltamivir administration, an anti influenza viruses A and B, on some functional parameters of rat liver were investigated, to evaluate the possible hepatotoxic effect. Eighteen (18) wister male albino rats with body weight ranged 150-190 gm were divided into three groups, the first group(T1) was treated orally with 1mg/kg.BW as therapeutic dose of Oseltamivir for 7consuctive days. The second group (T2) was treated with the same dose for six weeks, while the control group dosed distill water.The results revealed, there was a significant increase in the onset of barbiturate sleeping time and a significant p ≤ 0.05 decrease of the duration of barbiturate sleeping time of the T2 rats . The liver enzymes activity revealed a significant decrease in ALT in T1 rats and significant increased p<0.05 in the T2 rats, while the AST activity showed only significant increased p<0.05 in the T2 treated rats. The activity of ALP was p<0.05 significantly increased in the rats of treated groups. The blood sugar was significantly decreased p<0.05 only in the T2rats. Cholesterol level was significantly p<0.05 increased in T2 treated rats, while the serum of both treated groups showed a significantly increase p<0.05 in the triacylglycerol concentration.The HDL level was significantly decreased p<0.05 only in theT1 rats. The treated T2 rats showed a significant decrease p<0.05 in the LDL, while the VLDL level revealed a significant increase p<0.05.The total serum protein level was significantly increased p<0.05 in the rats of T2. Liver histopathological lesions of the T1rats revealed large amount of suppurative exudates, severe dilation and congestion of central veins and sinusoids with activation of kupffer cells. The liver of T2 rat showed multiple areas of focal necrosis, fibrous thickening of Glisson capsule with vacuolar degeneration of hepatic parenchyma. In:conclusion, Oseltamivir has hepatotoxic effect in rats treated with therapeutic dose 1mg/ kg.BW. orally in different periods.
Downloads
Article Details
How to Cite
References
-McNicholl, IR.andMcNicholl, JJ.(2001). Neuraminidase inhibitors: zanamivir and oseltamivir. Ann.Pharmacother., 35: 57-70.
-Bardsley-Elliot, A. and Noble, S.(1999).Oseltamivir.Drugs, 58:851–860.
-Shi, D.; Yang, J.; Yang, D.;LeCluyse, EL.; Black, C.; You, L.;Akhlaghi, F. and Yan, B.(2006).Anti-influenza prodrugoseltamivir is activated by carboxylesterase human carboxylesterase 1 and the activation is inhibited by antiplatelet agent clopidogrel. J.Pharmacol. Exp.Ther.,319:1477–1484.
-He, G.(1999).Clinical pharmacokinetics of the prodrugoseltamivirand its active metabolite Ro 64-0802.Clin.Pharmacokinet.
: 471-484.
-Roche Laboratories Inc. Tamiflu (oseltamivir phosphate): capsules and oral suspension prescribing information for the US.www.rocheusa.com.
-Wood,ND.; Aitken, M.; Sharp, S. andEvison, H.(1997).Tolerability and pharmacokinetics of the influenza neuraminidase inhibitor Ro-64-0802 (GS4071) following oral administration of the prodrug Ro-64-0796 (GS4104) to health male volunteers. 37th ICAAC., (Toronto,1997) .
- Roche Pharmaceuticals Laboratories. Tamiflu package insert (Oct27, 1999).
-Jones,AL. (1999).Anatomy of the normal liver .In: Hepatology , a text book of liver disease .Zakin D,Boyer TD , Eds,3rded , Pheladeliphia , WB Saunders,Pp: 3-32.
-Ostapowicz, G.; Fontana, PJ.andSchiodt, Fr. (2002).Results of a prospective study of acute liver failure at 17 tertiary cure Centers in the United States.Ann. Intern.Med., 137: 947-954.
- Zimmerman, HJ. (1999).Drug –induced liver disease In: The adverse effects of drugs and other chemicals on the Liver Zimmerman HJ ed.Hepatotoxicity:.2nded.Philadelphia, PA Lippincott William and Wilkins,Pp:427-456.
-Hafez, ES.(1970).Reproduction and breeding techniques for laboratory animals.Lea and Febiger, Philadelphia.
- Ferrini,R.;Miragoli, G.and Taccardi, B. (1974).Neuropharmacological studies on SB 5833 a new psychotherapeutic agent of the benzodiazepine class.Arzneim-Forsch, 24: 2029.
-Luna, LG. (1968).Manual of histology staining methods of Armed forces Institute of Pathology,3rded McGraw Hill Book Co New York,Pp:7-9.
-Trinder,P ,Ann.Clin.Biochem,16 24 (1969).
-Ricmond .Clin.Chem, 19 1350 (1973) .
- Fasce, CF.Clin.Chem, 18 901 (1982).
-TIETZ, NW. (1999).Text book of clinical chemistry 3rded. CA Burtis E R Ashwood W B Saunders, Pp:809 – 857 .
-Burstein, M. (1970). Lipid Res 11 583 Study group EuropeanAtheroseclerosis Society.Eur. heart J.,1988 .
- ARCOL ISB . (1989).15 , 121 – 124).
-Young, DS.(2000). Effect of drugs on clinical laboratory tests. 5thed P:46.Youra A Teel R W Stoner M (2007).Ellagic acid action against bacteria infection of H pyloriand antibacterial mechanism.Med. J.,30:329-336.
-Joda, M.(2008) .The progressive statistical analysis by using SPSS 1st editChurhilllivingstone Edinburgh, Pp:109-112.
-Parkinson,A. (2001).Biotransformation of xenobioticsIn:Casarett and DoullsToxicology. The Basic Science of poisoning (Klassen .CDed ) McGraw Componies New York,Pp:139-162 .
-Jian,Y.;Deshi,S.; Dong fang, Y.;Xiulong, S. and Binfang, Y. (2007).Interleukin-6 alters the cellular responsiveness toclopidgorelIrinotencan and oseltamivir by suppressing the expression of carsboxylesteraes HCE1 and HCE2.Mol. Pharm.,
(3):686-694.
-Musa,TY.;Lawal, SB.: Mansur, L. and Musban, AA.(2003).Evaluation of selected parameters of rat liver and kidney function following repeated administration of yohimbine. Biochm., 15 (2): 50-56.
-Thapa, BR. and Walia, O.(2007).Liver function tests and their interpretation.Indian J.pediatr.,74(7):663-671.
-Friedman,SF., Martin, P. and Manoz, JS.(2003). Laboratory evaluation of the patient with liver disease.In:Histopathologya text book of liver disease. Philadelphia,Sounders Publication.1, Pp: 661-709.
-Rosalk, SB. and Mcintyre, N.(1999).Biochemical investigations in the management of liver disease Oxford text book of clinical hepatology2nded. New York, Oxford University press.Pp: 503-521.
-Sherry, FQ. (2005). Systemic and CNS toxicities of antimicrobial agents In: The principals of Neurologic infectious diseases. Kuren,L. Roos. McGraw Hill, Pp: 497-508.
-Wael,ME.andMohemed, A.(2011). Potential adverse effects of oseltamivirin rats male are more vulnerable than females. Can. J. Physiol.Pharmacol., 23 (218):611-687.
-Shin- Hung,T.; Yen-Yuelin, C.;WangHsu,C.;Shang, C. and Der-Ming, C. (2011).Hypoglycemia revisited in the acute care setting.Yonsei Med. J., 52 (6): 898-908.
-Emma, L. (2009).CholestrolLipidomics Gateway.Doi., 10:1038.
-Jhon, S.;Sorokin, AV. and Thompson, D.(2007).Phytosterol and vascular diseases.Curr.Opin. Lipidol.,18(1): 35-40.
-Mead, JR.; Irvine,SA.andRamji, DP.(2002). Lipoprotein lipase structure function, regulation and role in disease. J. Mol. Med.,
(12): 753-69.
-Farrely,J. (2001). Pharmacologists' Review In: Center for drug evaluation and research. Application Number, 21-246.Pp:1-18.
-Daniel,SP.and Marshal, MK.(1999).Evaluation of the liver: Laboratory tests .Schiff's diseases of the liver 8thedUSA JB Lippincott publication :20-239.
-Daniel, SP.and Marshal, MK.(2007). Laboratory tests In: Schiff’s diseases of the liver 10thedVol 1 Eugene RS Michal FS Willis CM . Lippincott Wilkins 19-24.
-Larry, D. (2000).Drug- induced liver diseases. J.Hepatol., 32: 77-88.
-Michael, PH. and Cynthia, JA.(2006).Mechanism of drug-induced liver injury.The AAPs. J.8(1): 48- 54.
-Balazka, ME.; Wilmer, JL.; Holiday,SD.; Wilson ,RE.and Luster,ML.(1995).Role of proinflammatory Cytokines in acetaminophen hepatotoxicity Toxicol App 1 Pharmacol. , 133; 43-52.
-Balazka, ME., Elwell, MR., Holiday, SD., Wilson ,RE.and Luster, ML. (1996). Histology of acetaminophen induced liver changes: role of interleukin 1 alpha andtumor necrosis factor alpha.Toxicol.pathol., 24:181-189.
-Ishida, Y.;Konda, T.;Oshina, T.;Fujiwara, H.;Iwakura, Y. andMukaida, N. (2002).A pivotal involvement of IFN-gamma in the pathogenesis of acetaminophen –induced acute liver injury.FASEB.J.16: 1227-1236