Catechins prevents substance P-induced hyperactive bladder in rats via the downregulation of ICAM and ROS.
We previously reported substance P (SP) via neurokinin type 1 receptor facilitates bladder afferent signaling and reactive oxygen species (ROS) formation in bladder connected with neurogenic inflammation [Am. J. Physiol. Renal Physiol. 284 (2003) F840]. Increased intercellular adhesion molecule expression and subsequent leukocyte adhesion in the inflamed bladder contribute to SP-induced oxidative injury. Here we investigate the effect of green tea extract (catechins) on SP-induced bladder hyperactivity. We evaluated isovolumetric cystometrogram, adhesion molecular expression, and ROS activity in anesthetized rat bladder with SP stimulation. Our results showed that SP increased the amount of leukocyte ROS production in vitro in a dose-dependent manner and the enhanced ROS can be inhibited by catechins treatment. Exogenous SP increased ROS in vivo in the bladder via increased intercellular adhesion molecule expression and subsequent leukocyte adhesion, a primary source of ROS in the inflamed bladder. Two weeks of catechins pretreatment reduced SP-induced bladder intercellular adhesion molecule expression and ROS amount and ameliorated the hyperactive bladder response. These results indicate that catechins pretreatment can ameliorate SP-induced neurogenic inflammation via the action of antioxidant, anti-adhesion, and anti-inflammatory activity.
Department of Infectious Disease Control and Clinical Immunology, Nihon University School of Medicine, Tokyo, Japan.
Wang-Chuan
WC
Chen
Satoshi
S
Hayakawa
Kazufumi
K
Shimizu
Chiang-Ting
CT
Chien
Ming-Kuen
MK
Lai
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D002392:Catechin / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013373:Substance P; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000517:prevention & control*; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D015815:Cell Adhesion Molecules; D017382:Reactive Oxygen Species; D013373:Substance P; D002392:Catechin