Melatonin ameliorates bladder damage induced by cyclophosphamide in rats

Area of Science:

• Pharmacology
• Toxicology
• Biochemistry

Background:

• Cyclophosphamide (CP) is an antineoplastic agent known to cause urotoxicity, specifically hemorrhagic cystitis (HC).
• The pathogenesis of HC involves inflammation, cytokine production, inducible nitric oxide synthase (iNOS) induction, and reactive oxygen species (ROS) overproduction.
• Oxidative stress resulting from ROS contributes to cellular injury and apoptosis in the bladder.

Purpose of the Study:

• To investigate the protective effects of melatonin against CP-induced urinary bladder damage.
• To evaluate melatonin's role as an antioxidant, iNOS inhibitor, and peroxynitrite scavenger.

Main Methods:

• Thirty male Sprague-Dawley rats were divided into four groups: control, CP-only, and two groups receiving CP with different doses of melatonin.
• CP was administered intraperitoneally (100 mg/kg). Melatonin (5 or 10 mg/kg/day) was given before and after CP administration.
• Measurements included iNOS induction, malonyldialdehyde (MDA) levels, and urinary nitrite-nitrate excretion.

Main Results:

• CP administration led to increased iNOS induction, elevated bladder MDA levels, and higher urinary nitrite-nitrate excretion, indicating severe cystitis.
• Melatonin treatment significantly protected against CP-induced cystitis.
• Melatonin diminished bladder oxidative stress and inhibited iNOS and peroxynitrite production.

Conclusions:

• Oxidants play a significant role in the pathogenesis of CP-induced cystitis.
• Inducible nitric oxide synthase (iNOS) is a key mediator in producing peroxynitrite, contributing to bladder damage.
• Melatonin effectively ameliorates CP-induced urinary bladder damage, highlighting its therapeutic potential.