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Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
Feselol Ameliorates Acetaminophen-Induced Hepatotoxicity Through Multi-Pathway Modulation of Oxidative Stress,
Maryam Karimi-Dehkordi1, Firoozeh Saghaei1, Mohammad Saberian1
1Department of Veterinary, Shk.C., Islamic Azad University, Shahrekord, Iran.
Background And Aim:
Acetaminophen (APAP) overdose is a major cause of drug-related acute liver failure around the world. The limited treatment options beyond N-acetylcysteine (NAC) show a clear need for new liver-protective agents. Feselol, a natural compound known for its strong antioxidant effects, has become a potential candidate. This research aimed to evaluate feselol's anti-inflammatory, anti-apoptotic, and protective qualities against APAP-induced acute liver damage in a mouse model.
Material And Method:
The experiment included 42 mice divided into 7 groups, with some being administered a toxic dose of APAP only and others being given APAP in combination with 25 or 50 mg/kg of feselol. Serum levels of AST (serum aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), and GGT (gamma-glutamyl transferase) were examined. SOD (superoxide dismutase), CAT (catalase), GPx (glutathione peroxidase) activities and MDA (malondialdehyde) levels were measured by colorimetric method. The liver tissue was analyzed through H&E staining. The expression of IL-1β, TNF-α, Bax, Caspase 3, and Bcl-2 genes was also examined by Real-time PCR.
Results:
The results showed that treatment of feselol at different doses with APAP led to a decrease in MDA levels to 23.25 nmol/mg (p < 0.05). Also, the activities of SOD, CAT and GPx enzymes in the group treated with a dose of 50 mg/kg of feselol with APAP were 33.09, 109.86, and 109.80, respectively, which was significant compared to the APAP group (p < 0.05). The results showed that simultaneous treatment with feselol and APAP resulted in a decrease in IL-1β and TNF-α gene expression by 1.67 and 1.015 fold, respectively (p < 0.05). Also, the expression of Bax (3.22-fold) and Caspase 3 (1.26-fold) genes decreased in the feselol-treated group and the expression of Bcl-2 (0.59-fold) gene increased. In the group that received APAP and feselol, the liver tissue was close to that of the control group. Feselol (50 mg/kg) coadministered with APAP significantly reduced ALT, AST, ALP, and GGP enzyme activity compared to the APAP-treated group (p < 0.05).
Conclusion:
This study is notable for the discovery of feselol's pharmacological effects as a preventive drug against oxidative stress-associated hepatic impairment.
Insights
Feselol demonstrates significant liver-protective effects against acetaminophen-induced liver injury by reducing oxidative stress and inflammation. This natural compound offers a promising therapeutic strategy for acute liver damage.
Area of Science:
- Pharmacology
- Hepatology
- Natural Products Chemistry
Background:
- Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure globally.
- Existing treatments for APAP overdose are limited, highlighting the need for novel hepatoprotective agents.
- Feselol, a natural compound with potent antioxidant properties, is investigated as a potential therapeutic candidate.
Purpose of the Study:
- To evaluate the anti-inflammatory, anti-apoptotic, and protective effects of feselol against APAP-induced acute liver injury in a mouse model.
- To assess feselol's impact on key biomarkers of liver damage and oxidative stress.
- To examine the molecular mechanisms underlying feselol's hepatoprotective actions.
Main Methods:
- A mouse model of APAP-induced acute liver injury was established.
- Mice were treated with varying doses of feselol (25 or 50 mg/kg) in combination with APAP.
- Serum liver enzymes (AST, ALT, ALP, GGT), oxidative stress markers (SOD, CAT, GPx, MDA), and gene expression (IL-1β, TNF-α, Bax, Caspase 3, Bcl-2) were analyzed.
- Liver tissue histology was assessed using H&E staining.
Main Results:
- Feselol treatment significantly reduced malondialdehyde (MDA) levels and increased antioxidant enzyme activities (SOD, CAT, GPx).
- Feselol administration suppressed the expression of pro-inflammatory genes (IL-1β, TNF-α) and apoptosis-related genes (Bax, Caspase 3), while upregulating anti-apoptotic gene (Bcl-2).
- Histopathological examination revealed that feselol mitigated APAP-induced liver damage, preserving liver tissue integrity.
Conclusions:
- Feselol exhibits significant anti-inflammatory and anti-apoptotic properties.
- Feselol demonstrates potent hepatoprotective effects against APAP-induced liver injury.
- Feselol represents a promising therapeutic agent for preventing and treating oxidative stress-related hepatic impairment.
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