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AB0162 Protective Effects of Caffeic Acid Phenethyl Ester (CAPE) on Cyclophosphamide Induced Hemorrhagic Cystitis in Rats

Background Cyclophosphamide (CP) is commonly used chemotherapeutic agent in malignancies and rheumatic diseases. Hemorrhagic cystitis (HC) is a serious complication of CP treatment. CAPE, antioxidant and anti-inflammatory molecule, is a major component of honeybee propolis and structurally similar to flavonoids. Objectives We investigated the protective effect of Caffeic asit phenyl ester (CAPE) on cyclophosphamide (CP) induced hemorrhagic cystitis (HC) in rats in comparison with mesna Methods Forty male Wistar rat ages between 8-12 weeks were divided into four groups by random sampling method. HC induction was performed using an urotoxic dose of 100 mg/kg CP. Group 1 (Control) animals were injected with the same amount of saline and served as controls. Group 2 (CP) received only CP, group 3 (CP+mesna) received 100 mg/kg CP and mesna in dosage of 21,5 mg/kg which was given 20 minutes before, 4 and 8 hours after CP injection. Group 4 (CP+CAPE) received 100mg/kg CP and pretreated with CAPE (10 μmol/kg/day) at 48 and 24 hours and also 20 minutes before CP injection. All drugs were administered intraperitoneally. The bladder tissues were cut into two equal pieces from top to the bottom. One half was stored at -80°C for determination of SOD and CAT activities with MDA and NO concentration and the other half was fixed for 24 hr in 10% buffered formaldehyde for histological evaluation. Results Control animals had histologically normal bladders. CP caused severe microscopic mucosal injury in the bladder. Mesna exhibited significant histological protection against bladder damage of CP. CAPE had minimal protective effect on histological damage. CP injection which caused HC increased MDA levels indicating oxidative stres while CAPE and mesna ameliorated MDA levels in the bladder (p>0.05). SOD and CAT activities were decreased in the tissue samples of CP+mesna and CP+CAPE group. However, only CAT activities were decreased significantly in both groups (CP+mesna and CP+CAPE p<0.05). Pretreatment with CAPE (p<0.01) resulted in significant decrease in NO level when compared with CP group. Conclusions When we consider the studies which show the critical importance of increased NO levels in the pathogenesis of cyclophosphamide induced hemorrhagical cystitis, we suggest that it would be more benefical to use mesna with CAPE to prevent histological damage. References Korkmaz A, Oter S, Deveci S, Ozgurtas T, Topal T, Sadir S, Bilgic H. Involvement of nitric oxide and hyperbaric oxygen in the pathogenesis of cyclophosphamide induced hemorrhagic cystitis in rats. J Urol 2003;170:2498– 2502 Natarajan K, Singh S, Burke TR, Grunberger D, Aggrawal BB. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci U S A 1996:20;93(17): 9090–9095. Disclosure of Interest None declared