Hepatoprotective activity of the combination of Mesalazine and Metformin in a paracetamol-induced animal model in rats
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Author:
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AALIYA LIYAKATH ALI ROSHANARA, GAURAV MAHESH DOSHI
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Abstract:
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The most common cause of liver injury is drug-induced liver toxicity. The combination of Mesalazine and Metformin has been evaluated for their hepatoprotective effect against drug-induced liver injury caused by Acetaminophen (APAP) toxicity. The study was conducted using APAP (2000 mg/kg) induced hepatoxicity model for 28 days. The combination doses of Mesalazine 100mg/kg+Metformin 200mg/kg and Mesalazine 50mg/kg+Metformin 100mg/kg were studied. Furthermore, pharmacodynamic evaluation parameters such as liver Index, serum enzyme levels of ALP, SGPT, SGOT, LDH, total protein, GSH, MDA, TNF a, and 1ß levels were checked. Moreover, a histopathological examination of the liver was done to assess the effects of drugs. It was observed that liver index values were significant (##P<0.01) in comparison to the normal control group. The serum enzyme biomarker levels (ALP, SGPT, SGOT, LDH) were significantly decreased (## #P<0.001 when compared against the normal control group and ***p<0.001 when compared against disease control). Total protein levels were significantly increased in treated groups. The levels of GSH and MDA were significantly decreased and increased respectively (###p<0.001 when compared against normal control, ***p<0.001 when compared against disease control). Furthermore, significantly lower levels of TNF-a and IL-1ß levels were observed in Mesalazine and metformin-treated groups. Histology of the liver showed that severe hepatic lesions induced by APAP were effectively decreased by a combination of metformin and mesalamine. Thus, the selected combination of metformin and mesalamine protects rats against APAP hepatotoxicity and proves its potential as a hepatoprotective agent.
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Keyword:
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Acetaminophen, Hepatotoxicity, Glutathione, Malondialdehyde, Lactate Dehydrogenase, Serum glutamic oxaloacetic transaminase, Serum glutamic pyruvic transaminase, Tumor Necrosis Factor- a.
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EOI:
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-
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DOI:
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https://doi.org/10.31838/ijpr/2023.15.02.007
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