RESUMO
BACKGROUND AND OBJECTIVES: The therapeutic and protective effects of montelukast against amikacin-induced acute renal damage were investigated. MATERIAL AND METHODS: 35 Wistar albino female rats were divided into 5 groups as follows: Group I: Control; Group II: Control+montelukast; Group III: Amikacin; Group IV: Amikacin+montelukast; Group V: Montelukast+amikacin. At the end of the experiment, the kidney tissues and the blood of rats were collected. Malondialdehyde (MDA), myeloperoxidase (MPO), and reduced glutathione (GSH) levels were determined from kidney tissues. Blood urea nitrogen (BUN), creatinine (Cr), TNF-alpha, and IL-1beta levels were assessed in the serum. In addition the kidney tissues were examined histologically. RESULTS AND DISCUSSION: The MDA, MPO, BUN, and Cr levels of group III significantly increased when compared to groups I and II. These parameters of group IV decreased when compared to group III. In addition, GSH levels significantly increased when compared to the first three groups. MDA, BUN and Cr levels of group V did not reach significant level in comparison with the control group. The most significant histological damage was observed in the group III followed by the groups IV and V. Immunohistochemically, group III showed a significantly increased apoptotic staining. In group IV, it was observed that montelukast treatment reduced the expression of apoptotic cells. CONCLUSIONS: Montelukast treatment after amikacin injection could reduce the amikacin-induced kidney damage.
Assuntos
Acetatos/farmacologia , Amicacina , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Quinolinas/farmacologia , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Ciclopropanos , Citoproteção , Modelos Animais de Doenças , Feminino , Glutationa/metabolismo , Imuno-Histoquímica , Interleucina-1beta/sangue , Rim/metabolismo , Rim/patologia , Nefropatias/sangue , Nefropatias/induzido quimicamente , Nefropatias/patologia , Malondialdeído/metabolismo , Peroxidase/metabolismo , Ratos , Ratos Wistar , Sulfetos , Fator de Necrose Tumoral alfa/sangueRESUMO
Cyclophosphamide (CYC) and doxorubicin (DOX) are among the most effective and widely used anticancer chemotherapeutic drugs. Potential chemopreventive and chemotherapeutic functions have recently been attributed to flavonoids. We hypothesized that Quercetin (QR) would protect against the toxic effects of chemotherapeutic agents applied prior to pregnancy. Rats were treated with the chemotherapeutic drugs CYC (27 mg/kg) and DOX (1.8 mg/kg) applied in a single intraperitoneal dose once every 3 weeks for 10 weeks. QR was administered at a dose of 10 mg/kg/day by oral gavage. 48 h following the experimental chemotherapy exposure, female rats were transferred to cages containing male rat for mating. Fetal brain tissues were removed from fetuses extracted by cesarean section on the 20th day of gestation for evaluation of antioxidant parameters. A significant increase in superoxide dismutase and malondialdehyde activity was observed in CYC and DOX treatment groups relative to the control group (p < 0.05). Similarly, carnitine acylcarnitine translocase and Glutathione activity was significantly reduced in the CYC and DOX groups relative to the control group (p < 0.05). Our results indicate that the use of chemotherapeutic drugs before pregnancy can result in oxidative damage to fetal brain tissue. Therefore, women who have been exposed to chemotherapy and may become pregnant should be treated with antioxidant compounds such as QR to reduce the risk of damage to fetal brain tissues.