, Volume 18, Issue 2, pp 87–94 | Cite as

Hepatoprotective effects of the nitric oxide donor isosorbide-5-mononitrate alone and in combination with the natural hepatoprotectant, silymarin, on carbon tetrachloride-induced hepatic injury in rats

  • Omar Mohamed E. Abdel Salam
  • Amany A. Sleem
  • Nermeen Shafee
Research Article


The aim of this study was to investigate the effect of the nitric oxide donor isosorbide-5-mononitrate (5-ISMN) alone or in combination with the natural hepatoprotectant with anti-oxidant activity silymarin on the carbon tetrachloride (CCl4)-induced hepatic injury in rats. 5-ISMN (1.8, 3.6 or 7.2 mg/kg), silymarin (25 mg/kg) or 5-ISMN (1.8, 3.6 or 7.2 mg/kg) combined with silymarin was given once daily orally simultaneously with CCl4 and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. 5-ISMN given at the above doses conferred significant protection against the hepatotoxic actions of CCl4 in rats, reducing serum alanine aminotransferase (ALT) levels by 31.2, 39.3 and 61.6%, respectively, when compared with controls. Serum aspartate aminotransferase (AST) levels decreased by 19.8, 22.7 and 59.4%, respectively, while alkaline phosphatase (ALP) decreased by 26.1 and 32.6% by the drug at 3.6 and 7.2 mg/kg, respectively. When silymarin was added to 5-ISMN (1.8, 3.6 or 7.2 mg/kg), ALT decreased by 32.8, 59.6, 70.2% and AST by 28.7, 50.3, 60%, when compared with CCl4 control group levels. Silymarin in combination with 3.6 or 7.2 mg/kg 5-ISMN resulted in 37.5 and 39.2% reductions in ALP when compared with CCl4 control group. Meanwhile, silymarin alone reduced ALT, AST and ALP levels by 65.9, 52 and 62.3%, respectively. Blood levels of reduced glutathione were markedly decreased in CCl4-treated rats. Reduced glutathione levels were increased by the administration of 5-ISMN and restored to near normal values by silymarin treatment. Histopathological alterations by CCl4 were markedly reduced after treatment with 5-ISMN alone or in combination with silymarin. Histopathologic examination of the livers of CCl4-treated rats administered 5-ISMN at 7.2 mg/kg showed marked restoration of the normal architecture of the liver tissue and minimal fibrosis. Silymarin co-administered with 5-ISMN resulted in further improvement of the histologic picture. These results indicates that treatment with 5-ISMN protects against hepatocellular necrosis induced by CCl4. The study suggests a potential therapeutic use for 5-ISMN in combination with silymarin in liver injury.


Isosorbide-5-mononitrate Silymarin Acute hepatic injury Carbon tetrachloride Rat 


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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2010

Authors and Affiliations

  • Omar Mohamed E. Abdel Salam
    • 1
  • Amany A. Sleem
    • 1
  • Nermeen Shafee
    • 2
  1. 1.Department of PharmacologyNational Research CentreCairoEgypt
  2. 2.Department of PathologyNational Research CentreCairoEgypt

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