Melatonin mitigated methotrexate-induced hepatotoxicity through interrelated biological processes.
Mol Biol Rep
; 51(1): 833, 2024 Jul 22.
Article
en En
| MEDLINE
| ID: mdl-39039363
ABSTRACT
BACKGROUND:
Hepatotoxicity associated with methotrexate (MTX) is mainly due to disruption of redox balance and development of oxidative injury to hepatocytes. Melatonin (MLT) is a potent antioxidant and regulates wide range of biological functions, processes and utilized as adjuvant for number of medical applications. The current study investigated the mitigating effect of MLT on the MTX-induced hepatotoxicity. METHODS ANDRESULTS:
Adult male rats received MLT (25 mg/kg, orally) for seven days flowed by single injection of MTX (20 mg/kg, ip) then treat with MLT continued for additional 7 days. The present result showed MLT treatment mitigated histopathological changes in the liver that associated with normalization of ALT and AST activity as well as bilirubin, albumin and alfa-fetoprotein levels in serum of MLT + MTX-treated rat to comparable control level. MLT treatment significantly reduced MDA content and myeloperoxidase activity while enhanced the activity of superoxide dismutase, catalase and glutathione content in the liver indicating the empowerment of the antioxidant status. Amelioration of MLT-induced oxidative stress resulted in a reduction in the inflammatory response due to antioxidant restoration and inhibited apoptosis indicated by downregulation of caspase-3 expression. The replenishment of antioxidant content powers the defense system of the hepatocytes. As a result, apoptosis is reduced which might be due to the ability of MLT protect DNA integrity thus maintaining hepatocyte functions and structure. Consequently, liver histology was protected.CONCLUSIONS:
In summary, MLT modulates liver function and structure by orchestrating linked processes, including redox balance, inflammatory response, suppression of caspase-3, and DNA damage.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Metotrexato
/
Apoptosis
/
Estrés Oxidativo
/
Hepatocitos
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Enfermedad Hepática Inducida por Sustancias y Drogas
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Hígado
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Melatonina
/
Antioxidantes
Límite:
Animals
Idioma:
En
Revista:
Mol Biol Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Egipto