Melatonin mitigated methotrexate-induced hepatotoxicity through interrelated biological processes

Area of Science:

• Biochemistry
• Toxicology
• Pharmacology

Background:

• Methotrexate (MTX) causes liver damage primarily through oxidative stress.
• Melatonin (MLT) is a potent antioxidant with diverse biological functions.
• This study explores MLT's protective effects against MTX-induced hepatotoxicity.

Purpose of the Study:

• To investigate the mitigating effects of melatonin on methotrexate-induced liver injury.
• To evaluate the impact of melatonin on oxidative stress markers and liver function enzymes.
• To assess melatonin's role in modulating inflammatory and apoptotic pathways in the liver.

Main Methods:

• Adult male rats were administered melatonin orally for seven days.
• A single intraperitoneal injection of methotrexate was given, followed by continued melatonin treatment.
• Histopathological changes, liver enzymes (ALT, AST), serum proteins, oxidative stress markers (MDA, SOD, catalase, glutathione), and apoptosis markers (caspase-3) were analyzed.

Main Results:

• Melatonin treatment significantly reduced liver damage and normalized liver enzyme and protein levels.
• MLT administration enhanced antioxidant capacity by increasing SOD, catalase, and glutathione, while decreasing MDA.
• Melatonin suppressed inflammatory responses and inhibited apoptosis by downregulating caspase-3 expression, preserving liver structure and function.

Conclusions:

• Melatonin effectively mitigates methotrexate-induced hepatotoxicity.
• MLT protects liver function and structure by improving redox balance and reducing inflammation and apoptosis.
• Melatonin demonstrates potential as an adjuvant therapy for managing MTX-related liver injury.