RESUMO
BACKGROUND: The aim of this study was to establish the protective effect of caffeic acid phenethyl ester (CAPE) against the ifosfamide (IFOS)-induced central neurotoxicity in rats and to determine the changes in oxidant-antioxidant status of brain tissue. METHOD: A total of 35 Wistar rats (aged 7-12 days) were used in the experiments. The study comprised of five groups. Control untreated rats (n = 7) belonged to group 1; group 2 was given intraperitoneal (IP) injection of CAPE alone (10 µmol/kg; n = 7); group 3 was treated with single IP injection of IFOS (500 mg/kg; n = 7); group 4 was treated for 2 days with IP administration of CAPE (10 µmol/kg) beginning from one day before single IP injection of IFOS (n = 7); and group 5 was treated with saline and 10% ethanol. At the 24th hour of IFOS treatment, brain tissues were removed for analysis. RESULTS: The brain catalase activity was lower in IFOS group than the other groups (p < 0.05). The levels of malondialdehyde (MDA) and protein carbonyl content in brain tissue were higher in IFOS group than the control, CAPE, ethanol, and IFOS + CAPE groups (p < 0.05). There was no significant difference between MDA and protein carbonyl content of control, CAPE, ethanol, and IFOS + CAPE groups. Immunohistochemistry showed marked activation of caspase 3 in the IFOS group at 24 h after treatment. CONCLUSION: This study revealed that pretreatment with CAPE might protect brain tissue against IFOS-induced central neurotoxicity. CAPE could be an effective course of therapy to enhance therapeutic efficacy and to lessen IFOS toxicity in clinical chemotherapy.
Assuntos
Ácidos Cafeicos/farmacologia , Ifosfamida/toxicidade , Síndromes Neurotóxicas/tratamento farmacológico , Álcool Feniletílico/análogos & derivados , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/metabolismo , Imuno-Histoquímica , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/farmacologia , Carbonilação Proteica , Ratos , Ratos WistarRESUMO
OBJECTIVE: The aim of the present study is to investigate the efficiency of colchicine in the experimental rat ovarian torsion model in the light of histological and biochemical data. STUDY DESIGN: A total of 35 Wistar albino female rats were randomly divided into 5 groups, group 1: (control-sham operated, n = 7); group 2: (torsion/detorsion, n = 7) 2 hours of ischemia and 2 hours of reperfusion; group 3: (torsion/detorsion, n = 7), 2 hours of ischemia and 5 days of reperfusion; group 4: (torsion/detorsion, n = 7) 2 hours of ischemia and 2 hours of reperfusion and a signal dose of oral 1 mL/kg colchicine; and group 5: (torsion/detorsion, n = 7), 2 hours of ischemia and 5 days of reperfusion and 5 days of oral 1 mg/kg colchicine. Histopathologic evaluation was performed by a scoring that assesses congestion, bleeding, edema, and cellular degeneration in the ovarian tissue. Catalase, tissue malondialdehyde (MDA), and protein carbonyl levels were calculated. RESULTS: The histopathologic scores, MDA, and protein carbonyl levels in the control and colchicine groups were significantly lower than groups 2 and 3 (P < .001). Catalase activities were significantly higher in the control and colchicine groups than in groups 2 and 3 (P < .001). The results of the histopathologic parameters and biochemical markers showed that protective effects of colchicine treatment persisted up to 5 days. CONCLUSION: Our study results revealed that colchicine reduced ovarian ischemia-reperfusion injury in experimental rat ovarian torsion model. As the ovarian detorsion is the first choice of the treatment modality in the early phase, antioxidant and anti-inflammatory treatment modalities like colchicine might be used to reduce ovarian ischemia-reperfusion injury.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Colchicina/farmacologia , Doenças Ovarianas/tratamento farmacológico , Ovário/efeitos dos fármacos , Traumatismo por Reperfusão/terapia , Anormalidade Torcional/tratamento farmacológico , Animais , Catalase/metabolismo , Citoproteção , Modelos Animais de Doenças , Feminino , Malondialdeído/metabolismo , Doenças Ovarianas/complicações , Doenças Ovarianas/metabolismo , Doenças Ovarianas/patologia , Ovário/irrigação sanguínea , Ovário/metabolismo , Ovário/patologia , Carbonilação Proteica , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fatores de Tempo , Anormalidade Torcional/complicações , Anormalidade Torcional/metabolismo , Anormalidade Torcional/patologiaRESUMO
AIM: The aim of the study was to investigate the effectiveness of zofenopril in an experimental model of ovarian torsion in rats with histologic and biochemical assessments. MATERIAL AND METHODS: Experimental procedures were performed on 35 female rats (Wistar albino). Rats were randomly divided into five groups as: sham (sham operated, n = 7); vehicle group 1 (torsion-detorsion, n = 7) with 2 h ischemia and 2 h reperfusion; vehicle group 2 (torsion-detorsion, n = 7) with 2 h ischemia and 5 days' reperfusion; zofenopril group 1 (torsion-detorsion, n = 7) with 2 h ischemia, 2 h reperfusion and a signal dose of oral 15 mg/kg zofenopril; and zofenopril group 2 (torsion-detorsion, n = 7) with 2 h ischemia, 5 days' reperfusion and 5 days' oral 15 mg/kg zofenopril. A scoring of histopathologic evaluation was performed on the ovaries according to congestion, bleeding, edema, and cellular degeneration. Biochemical assessments included catalase, tissue malondialdehyde and protein carbonyl. RESULTS: Compared with the vehicle groups, histopathologic scores, tissue malondialdehyde and protein carbonyl levels, which reflect oxidative stress markers, were significantly lower in the zofenopril groups. Furthermore, catalase levels were significantly increased in the zofenopril group. CONCLUSION: Our study results revealed that zofenopril attenuates injury induced by ischemia-reperfusion on rat ovary.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antioxidantes/uso terapêutico , Captopril/análogos & derivados , Doenças Ovarianas/prevenção & controle , Ovário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Biomarcadores/metabolismo , Captopril/administração & dosagem , Captopril/uso terapêutico , Catalase/antagonistas & inibidores , Catalase/metabolismo , Relação Dose-Resposta a Droga , Feminino , Malondialdeído/antagonistas & inibidores , Malondialdeído/metabolismo , Doenças Ovarianas/etiologia , Doenças Ovarianas/metabolismo , Doenças Ovarianas/patologia , Ovário/irrigação sanguínea , Ovário/metabolismo , Ovário/patologia , Carbonilação Proteica/efeitos dos fármacos , Distribuição Aleatória , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Torção MecânicaRESUMO
Ifosfamide (IFOS) which is a cytotoxic alkylating agent may cause central nervous system toxicity. Alpha-lipoic acid (ALA) has a strong antioxidant effects. We hypothesized that ALA could attenuate on ifosfamide-induced central neurotoxicity in rats. Rats were divided into Control, IFOS, ALA and IFOS+ALA groups. The toxic effects of IFOS were analyzed by oxidative parameters and caspase 3 immunohistochemical examinations of brain tissue. The catalase activity of IFOS group significantly reduced in comparison with control groups (p < 0.05). The malondialdehyde (MDA) level and protein carbonyl (PC) content in brain tissue were significantly higher in IFOS group than in the other groups (p < 0.05). ALA treatments significantly prevented the increase in MDA level (p < 0.001) and PC content (p < 0.05) in brain tissue. IFOS group showed profound activation of caspase 3. The control, ALA and IFOS+ALA groups did not show caspase 3 activation. It was concluded that ALA treatments may have beneficial effects protecting neurons from central neurotoxicity caused by IFOS.