OBJECTIVE: Doxorubicin is a recognized chemotherapeutic agent widely employed in human malignancies. The limiting factor of its use is a number of side effects. The aim of this work was to show, whether administration of doxorubicin could induce behavioral disturbances in rats, and whether angiotensin-converting enzyme inhibitor captopril or melatonin can modify these potential alterations. DESIGN AND METHODS: Four groups of 3-month-old Wistar rats (twelve per group) were treated for 4 weeks: control (placebo-treated), doxorubicin (DOX) (5mg/kg i.v. in a single intravenous dose), DOX rats treated with either melatonin (10mg/kg/24h) or captopril (100mg/kg/24h). Systolic blood pressure (SBP) and the level of oxidative stress were investigated and behavioral tests of anxiety-open field test (OF), elevated plus maze (EPM) and light-dark box (LDB) were accomplished. RESULTS: Doxorubicin increased significantly systolic blood pressure and parameters of oxidative stress. Moreover, doxorubicin enhanced the level of anxiety in the tests of OF, EPM, and LDB. Captopril and melatonin prevented the blood pressure rise and the enhancement of oxidative load. Importantly, both substances reduced the parameters of anxiety. CONCLUSION: Chronic administration of captopril or melatonin has shown anxiolytic effect in the model of doxorubicin-induced anxiety. It does not seem unreasonable to suppose that this protective effect of captopril or melatonin against anxiety development might have been related to the antioxidative effects of both substances.

• MeSH
• antagonismus léků MeSH
• antibiotika antitumorózní farmakologie   MeSH
• biologické markery metabolismus   MeSH
• chování zvířat účinky léků   MeSH
• doxorubicin farmakologie   MeSH
• kaptopril farmakologie   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• melatonin farmakologie   MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chronic kidney disease (CKD) represents a serious public health problem with increasing prevalence and novel approaches to renal protection are continuously under investigation. The aim of this study was to compare the effect of melatonin and angiotensin II type 2 receptor agonist compound 21 (C21) to angiotensin converting enzyme inhibitor captopril and angiotensin II type 1 receptor blocker olmesartan on animal model of doxorubicin nephrotoxicity. Six groups of 3-month-old male Wistar rats (12 per group) were treated for four weeks. The first group served as a control. The remaining groups were injected with a single dose of doxorubicin (5 mg/kg i.v.) at the same day as administration of either vehicle or captopril (100 mg/kg/day) or olmesartan (10 mg/kg/day) or melatonin (10 mg/kg/day) or C21 (0.3 mg/kg/day) was initiated. After four week treatment, the blood pressure and the level of oxidative stress were enhanced along with reduced glomerular density and increased glomerular size. Captopril, olmesartan and melatonin prevented the doxorubicin-induced increase in systolic blood pressure. All four substances significantly diminished the level of oxidative burden and prevented the reduction of glomerular density and modestly prevented the increase of glomerular size. We conclude that captopril, olmesartan, melatonin and C21 exerted a similar level of renoprotective effects in doxorubicin-induced nephrotoxicity.

• MeSH
• antioxidancia terapeutické užití   MeSH
• blokátory receptoru 1 pro angiotenzin II terapeutické užití   MeSH
• chronická renální insuficience chemicky indukované   farmakoterapie   patofyziologie   MeSH
• doxorubicin MeSH
• hodnoty glomerulární filtrace účinky léků   MeSH
• imidazoly terapeutické užití   MeSH
• inhibitory ACE terapeutické užití   MeSH
• kaptopril terapeutické užití   MeSH
• krysa rodu rattus MeSH
• ledvinné látky terapeutické užití   MeSH
• melatonin terapeutické užití   MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• receptor angiotensinu typ 2 agonisté   MeSH
• tetrazoly terapeutické užití   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NO-production L-arginine were able to reverse the protein rebuilding of the left ventricle. Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginine-regression (4 weeks L-NAME + 3 weeks arginine), control 7 (7 weeks placebo). L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic and contractile as well as soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison with the control group. The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone.

• MeSH
• antagonisté mineralokortikoidních receptorů farmakologie   terapeutické užití   MeSH
• arginin farmakologie   terapeutické užití   MeSH
• hypertenze chemicky indukované   komplikace   farmakoterapie   metabolismus   patofyziologie   MeSH
• hypertrofie levé komory srdeční farmakoterapie   etiologie   metabolismus   patofyziologie   MeSH
• kolagen metabolismus   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• myokard metabolismus   patologie   MeSH
• NG-nitroargininmethylester MeSH
• oxid dusnatý metabolismus   MeSH
• potkani Wistar MeSH
• remodelace komor účinky léků   MeSH
• spironolakton farmakologie   terapeutické užití   MeSH
• spontánní remise MeSH
• svalové proteiny metabolismus   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH