Ability of cyclohexenonic long-chain fatty alcohol to reverse diabetes-induced cystopathy in the rat.
OBJECTIVE
We investigated the ability of 3-(15 hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen 1-one (N-hexacosanol), a neurotrophic substance, to reverse diabetes-induced cystopathy in the rat.


METHODS
Eight-week-old male Sprague-Dawley rats were divided randomly into four age-matched groups. In three of these groups, diabetes was induced by streptozotocin (STZ; 50mg/kg intraperitoneal [IP]). Four weeks after the induction of diabetes, the three groups received another 4 weeks of treatment by vehicle or N-hexacosanol (2 or 8 mg/kg IP every day). The serum glucose and serum insulin levels were determined, and the bladder functions were estimated by voiding behavior studies, cystometric studies, and functional studies using carbachol and KCl. The participation levels of M(2) and M(3) receptors were investigated by real-time polymerase chain reaction and immunohistochemical staining. Typical hematoxylin-eosin staining was also performed.


RESULTS
Treatment with N-hexacosanol did not alter the rats' diabetic status, but did significantly improve the diabetes-induced dysfunction of the detrusor in a dose-dependent manner. Furthermore, N-hexacosanol significantly reversed the upregulation of muscarinic M(2) and M(3) receptor messenger RNAs (mRNAs) in STZ-diabetic rats. Muscarinic M(2) and M(3) receptors were localized in detrusor and urothelium, and there was no difference between any of the groups in the distribution of muscarinic M(2) and M(3) receptors.


CONCLUSIONS
These results indicate that N-hexacosanol has a beneficial effect on hyperreactivity in the diabetic detrusor by ameliorating overexpression of muscarinic M(2) and M(3) receptor mRNAs.
Saito
Motoaki
M
Department of Pathophysiological and Therapeutic Science, Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Yonago, Japan. saitomo@grape.med.tottori-u.ac.jp <saitomo@grape.med.tottori-u.ac.jp>
Kinoshita
Yukako
Y
Satoh
Itaru
I
Shinbori
Chiko
C
Suzuki
Hiroto
H
Yamada
Masashi
M
Watanabe
Takeshi
T
Satoh
Keisuke
K
D000818:Animals; D003512:Cyclohexanones / Q000627:therapeutic use*; D048909:Diabetes Complications / Q000188:drug therapy*; D005233:Fatty Alcohols / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D001745:Urinary Bladder Diseases / Q000188:drug therapy*
C420963:3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen-1-one; D003512:Cyclohexanones; D005233:Fatty Alcohols