Melatonin protects against methotrexate hepatotoxicity in young rats: Impact of PI3K/Akt/mTOR signaling

Area of Science:

• Pediatric Oncology
• Hepatology
• Pharmacology

Background:

• Improved survival rates in childhood acute lymphoblastic leukemia (ALL) are linked to treatments like methotrexate (MTX).
• Intrathecal MTX is crucial for leukemia patients, but hepatotoxicity is a known side effect of MTX therapy.
• Understanding MTX's hepatic effects, especially via the intrathecal route, is vital for patient safety.

Purpose of the Study:

• To investigate the pathogenesis of methotrexate-induced hepatotoxicity in young rats.
• To evaluate the protective potential of melatonin against MTX-induced liver injury.
• To explore melatonin as a therapeutic agent for mitigating MTX hepatotoxicity.

Main Methods:

• Induction of hepatotoxicity using intrathecal methotrexate in a young rat model.
• Administration of melatonin to assess its protective effects.
• Histopathological and biochemical analyses to evaluate liver damage and protection.

Main Results:

• Intrathecal methotrexate administration led to significant hepatic damage in young rats.
• Melatonin treatment demonstrated a protective effect against MTX-induced hepatotoxicity.
• Biochemical markers indicated reduced liver injury in rats treated with melatonin.

Conclusions:

• Melatonin can effectively protect against liver damage induced by intrathecal methotrexate.
• Melatonin represents a promising therapeutic strategy for managing MTX-related hepatotoxicity in pediatric leukemia treatment.
• Further research is warranted to translate these findings into clinical practice for children undergoing leukemia therapy.