title: Inhibitory activity of α-tocopherol on apoptosis in the rat bladder wall subjected to androgen deprivation.
abstract: Alpha-tocopherol (2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-chromon-8-ol) is used in many previous urological studies. Thus to add to this knowledge in this study we studied the potential inhibitory activity on oxidative stress and process apoptosis on bladder wall in male rats subjected to androgen deprivation. A causal relationship between lower testosterone levels and apoptosis, as a component of castration-induced muscle atrophy, has been shown. Male Wistar rats (250-300 g) were used in this experiment, divided into four groups: control (sham operation; n=10); castration (n=10); castration, with alpha-tocopherol supplementation over preceding four weeks (n=10); and castration, with alpha-tocopherol supplementation over preceding four weeks and subsequent eight weeks (n=10). Activated caspase-3 was detected using a previously described technique, with analysis using stereological methodology. Nonparametric methods were used to test statistical significance, taking a significance level of P<0.005. This study was approved by the ethics committee of the university where the project was developed. The serum testosterone concentrations before castration were less than 20 pg/ml. Analysis of 8-isoprostane showed statistical significance (P<0.0003). The volumetric density of caspase-3 showed significant differences between the groups. There was no statistical significance regarding caspase-3 between sham and alpha-tocopherol plus castration or between the groups that received alpha-tocopherol supplementation. The observations showed that there was greater apoptosis in the group with castration alone than in the groups with alpha-tocopherol supplementation. This finding, together with the induced androgen deprivation and higher 8-isoprostane levels, corroborates the hypothesis that alpha-tocopherol supplementation has an important protective effect under conditions of oxidative stress, thereby avoiding the apoptotic process, especially regarding aging.
authors.affiliation: Division of Geriatric Urology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Luana
authors.initials: L
authors.lastname: Ludwig
authors.forename: Deborah
authors.initials: D
authors.lastname: Seraphim
authors.forename: Fábio
authors.initials: F
authors.lastname: Lorenzetti
authors.forename: Ricardo Pimenta
authors.initials: RP
authors.lastname: Bertolla
authors.forename: Valdemar
authors.initials: V
authors.lastname: Ortiz
authors.forename: Miriam
authors.initials: M
authors.lastname: Dambros
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D009919:Orchiectomy; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; C075750:8-epi-prostaglandin F2alpha; D013739:Testosterone; D015237:Dinoprost; D053148:Caspase 3; D024502:alpha-Tocopherol