Carvedilol alleviates the detrimental effects of azathioprine on hepatic tissues in experimental rats: Focusing on redox system, inflammatory and apoptosis pathways.
Hum Exp Toxicol
; 43: 9603271241269003, 2024.
Article
in En
| MEDLINE
| ID: mdl-39080824
ABSTRACT
PURPOSE:
Drug-induced liver injury is becoming an increasingly important topic in drug research and clinical practice. Due to a lack of experimental animal models, predicting drug-induced liver injury in humans is challenging. Azathioprine (AZA) is a classical immunosuppressant with hepatotoxic adverse effects. The present study aimed to address the hepatoprotective effect of carvedilol (CAR) against AZA-induced hepatocellular injury via assessing redox-sensitive signals.METHOD:
To achieve this purpose, rats were allocated into four groups control, CAR only, AZA only, and CAR plus AZA groups. The induction of hepatic injury was induced by a single intraperitoneal injection of AZA at a dose of 50 mg/kg on the 6th day of the experiment. Each experimental protocol was approved and supervised by the Ethics Committee for Animal Experiments.RESULTS:
The results of the present study revealed that CAR administration significantly diminished AZA-induced hepatic dysfunction, as evidenced by relief of hepatic function biomarkers and histopathological aberration induced by AZA injection. Besides, CAR restored oxidant/antioxidant balance as well as NRF2 expression. In addition, CAR suppressed inflammatory response induced by AZA challenge as evidenced by downregulation of TLR4, TNF-α, MPO, and eNOS/iNOS levels in hepatic tissue. Moreover, CAR recovered apoptotic/anti-apoptotic status by modulation of caspase-3/Bcl2 expression.CONCLUSION:
Taken together, CAR protects against AZA-induced hepatic injury via antioxidant, anti-inflammatory, and anti-apoptotic activities. These findings revealed that CAR could be a good candidate for hepatic injury protection and can be added to AZA therapeutic regimen to reduce their adverse effect.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxidation-Reduction
/
Azathioprine
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Apoptosis
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Chemical and Drug Induced Liver Injury
/
Carvedilol
/
Liver
Limits:
Animals
Language:
En
Journal:
Hum Exp Toxicol
Year:
2024
Document type:
Article