Effect of melatonin on chronic bladder-ischaemia-associated changes in rat bladder function.
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: There are many studies showing melatonin's potent endogenous free radical scavenging and antioxidative properties, which protect against oxidative insult, but there is no information about the effect of chronic treatment with melatonin on oxidative-stress-related bladder dysfunction caused by chronic ischaemia. The model used in this study shows that functional and morphological changes caused by chronic bladder ischaemia and oxidative stress were protected by chronic treatment with melatonin, resulting in improvement of bladder hyperactivity.


OBJECTIVE
To investigate the potential therapeutic benefit of melatonin for chronic ischaemia-related bladder dysfunction.


METHODS
Adult male Sprague-Dawley rats were divided into control, arterial injury (AI), AI with low-dose melatonin treatment (AI-ML) and AI with high-dose melatonin treatment (AI-MH) groups. The AI, AI-ML and AI-MH groups underwent a procedure to induce endothelial injury of the iliac arteries and received a 2% cholesterol diet after AI. The rats in the AI-ML and AI-MH groups were treated with melatonin 2.5 or 20 mg/kg/day orally for 8 weeks after AI. The control group received a regular diet. After 8 weeks, urodynamic investigations were performed. Bladder tissues and iliac arteries were processed for pharmacological studies, and for immunohistochemical and histological examination.


RESULTS
Iliac arteries from AI, AI-ML and AI-MH rats displayed neo-intimal formation and luminal occlusion. In the AI group, the micturition interval was significantly shorter, and bladder capacity and voided volume were lower than in the controls. Contractile responses of bladder strips to KCl, electrical field stimulation and carbachol were significantly lower after AI than in the controls. The AI bladders were found to have a significantly increased collagen ratio, oxidative stress and inducible nitric oxide synthase (NOS) expression, and decreased constitutive NOS expression compared with the controls. In the AI-ML and AI-MH groups, neo-intimal formation was not prevented, but there were beneficial effects on bladder function and morphology. In the AI-ML group, the beneficial effects failed to reach statistical significance. In the AI-MH group, melatonin significantly improved oxidative stress and NOS expression, and there were significant improvements in all the functional and morphological variables compared with the AI group.


CONCLUSIONS
Arterial occlusive disease may lead to chronic bladder ischaemia and bladder hyperactivity associated with oxidative stress. In the model used, chronic treatment with melatonin protected bladder function and morphology, probably through its free radical scavenging and antioxidative properties. Melatonin may prevent oxidative damage and improve ischaemia-related bladder dysfunction.
Department of Urology, Fukushima Medical University School of Medicine, Fukushima City, Japan. mnomiya44@gmail.com
Masanori
M
Nomiya
David Mark
DM
Burmeister
Norifumi
N
Sawada
Lysanne
L
Campeau
Mona
M
Zarifpour
Osamu
O
Yamaguchi
Karl-Erik
KE
Andersson
D000818:Animals; D002908:Chronic Disease; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
D008550:Melatonin