Effect of Fructose in Acetaminophen Induced Liver Injury in Rats

Objective: Low dose fructose was used in hepatotoxic rats to assess its hepatoprotective role. The objective of this studywas to assess the effect o f fructose on liver function using enzyme assays and morphologic changes. Study Design: Quasi-Experimental studyPlace and Duration of Study: Departments of Biochemistry, Pharmacology and Pathology, Army Medical College andNational Institute ofHealth from Jan 2007-Jan 2008. Methodology: One hundred and twenty healthy male Sprague-Dawley rats were injected Acetaminophen (APAP) (650mg/kg) to induce acute hepatotoxicity, fructose (1g/kg) and N-acetyl cysteine (NAC) (1200 mg/kg) intraperitoneally.Blood samples ware taken after ten hours and serum was separated and centrifuged. Serum alanine aminotranferase(ALT), aspartate aminotransferase (AST), alkaline phosphatase , albumin and total bilirubin were measured using kitmethod. Liver biopsy was taken to observe the necrotic changes. Results: APAP had 200% elevation of serum ALT and AST (p 0.05). Fructose and APAP co-administration (group III)had insignificant effect on serum ALT (p= 0.6) and AST (p= 0.9) as compared to APAP group (p>0.05). NAC (groupIV) significantly decreased serum transaminases compared to groups II and III (p<0.01). Fructose did not reducecentrilobular necrosis produced by APAP, while NAC had significant cytoprotection in this animal model. Conclusion: Low dose fructose (1g/kg) has no hepatoprotective role in acute APAP hepatotoxicity in vivo and NACconferred hepatoprotection. Additional studies are needed to understand the combined interaction of fructose and APAP,as fructose is being extensively consumed by general population in form o f commercial beverages.

[1]  G. Livesey Fructose ingestion: dose-dependent responses in health research. , 2009, The Journal of nutrition.

[2]  E. Schaefer,et al.  Dietary fructose and glucose differentially affect lipid and glucose homeostasis. , 2009, The Journal of nutrition.

[3]  R. Hoffman,et al.  Acetaminophen Overdose with Altered Acetaminophen Pharmacokinetics and Hepatotoxicity Associated with Premature Cessation of Intravenous N-Acetylcysteine Therapy , 2008, The Annals of pharmacotherapy.

[4]  M. H. Najmi,et al.  Pharmacological basis for use of Pistacia integerrima leaves in hyperuricemia and gout. , 2008, Journal of ethnopharmacology.

[5]  A. Koc,et al.  The protective effect of N‐acetylcysteine against cyclosporine A‐induced hepatotoxicity in rats , 2008, Journal of applied toxicology : JAT.

[6]  I. Zavodnik,et al.  Protective effects of N‐acetyl‐L‐cysteine against acute carbon tetrachloride hepatotoxicity in rats , 2008, Cell biochemistry and function.

[7]  M. Trauner,et al.  Clinical hepatotoxicity. Regulation and treatment with inducers of transport and cofactors. , 2007, Molecular pharmaceutics.

[8]  Y. Takei,et al.  Role of apoptosis in acetaminophen hepatotoxicity , 2007, Journal of gastroenterology and hepatology.

[9]  A. Wendel,et al.  ATP-Depleting Carbohydrates Prevent Tumor Necrosis Factor Receptor 1-Dependent Apoptotic and Necrotic Liver Injury in Mice , 2007, Journal of Pharmacology and Experimental Therapeutics.

[10]  M. Yüksel,et al.  Simvastatin attenuates cisplatin-induced kidney and liver damage in rats. , 2007, Toxicology.

[11]  M. Valentovic,et al.  Comparison of S-Adenosyl-l-methionine and N-Acetylcysteine Protective Effects on Acetaminophen Hepatic Toxicity , 2007, Journal of Pharmacology and Experimental Therapeutics.

[12]  A. Ogata,et al.  ATP-generating glycolytic substrates prevent N-nitrosofenfluramine-induced cytotoxicity in isolated rat hepatocytes. , 2006, Chemico-biological interactions.

[13]  M. Kirk,et al.  Updates on acetaminophen toxicity. , 2005, The Medical clinics of North America.

[14]  A. Gilani,et al.  Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents. , 2004, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[15]  Kumar Ganesan,et al.  Hepatoprotective activity of Trianthema portulacastrum L. against paracetamol and thioacetamide intoxication in albino rats. , 2004, Journal of ethnopharmacology.

[16]  J. Jordan,et al.  Fructose-Fed Rats Are Protected against Ischemia/Reperfusion Injury , 2003, Journal of Pharmacology and Experimental Therapeutics.

[17]  Laura P James,et al.  Acetaminophen-induced hepatotoxicity. , 2003, Drug metabolism and disposition: the biological fate of chemicals.

[18]  K. Eschrich,et al.  Fructose inhibits apoptosis induced by reoxygenation in rat hepatocytes by decreasing reactive oxygen species via stabilization of the glutathione pool. , 2002, Biochimica et biophysica acta.

[19]  Marcel Leist,et al.  Metabolic Depletion of Atp by Fructose Inversely Controls Cd95- and Tumor Necrosis Factor Receptor 1–Mediated Hepatic Apoptosis , 2000, The Journal of experimental medicine.

[20]  N. Lago,et al.  Cholestasis as a liver protective factor in paracetamol acute overdose. , 1995, General pharmacology.

[21]  J. N. Davidson,et al.  Fructose metabolism in the intact animal. , 1936, The Biochemical journal.

[22]  J. Sajedianfard,et al.  Therapeutic effects of cimetidine on acetaminophen-induced hepatotoxicity in rats , 2006, Comparative Clinical Pathology.