Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats

The frequent use of nonsteroidal anti-inflammatory drugs (NSAID) in combination with gentamicin poses the additional risk of nephrotoxic renal failure. Cyclooxygenase-1 (COX-1) is the main enzyme responsible for the synthesis of renal vasodilator prostaglandins, while COX-2 participates predominantly in the inflammatory process. Both are inhibited by non-selective NSAID such as indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer renal side effects than non-selective inhibitors. The objective of the present study was to determine whether the combined use of rofecoxib and gentamicin can prevent the increased renal injury caused by gentamicin and indomethacin. Male Wistar rats (250-300 g) were treated with gentamicin (100 mg/kg body weight, ip, N = 7), indomethacin (5 mg/kg, orally, N = 7), rofecoxib (1.4 mg/kg, orally, N = 7), gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively) or gentamicin + indomethacin (100 and 5 mg/kg, respectively, N = 8) for 5 days. Creatinine clearance and alpha-glutathione-S-transferase concentrations were used as markers of renal injury. Animals were anesthetized with ether and sacrificed for blood collection. The use of gentamicin plus indomethacin led to worsened renal function (0.199 ± 0.019 ml/min), as opposed to the absence of a nephrotoxic effect of rofecoxib when gentamicin plus rofexicob was used (0.242 ± 0.011 ml/min). These results indicate that COX-2-selective inhibitors can be used as an alternative treatment to conventional NSAID, especially in situations in which risk factors for nephrotoxicity are present.Universidade de São Paulo Escola de Enfermagem Laboratório ExperimentalUniversidade de São Paulo Faculdade de Medicina Laboratório de Investigação MédicaUniversidade Federal de São Paulo (UNIFESP) Departamento de Clínica Médica Divisão de NefrologiaUNIFESP, Depto. de Clínica Médica Divisão de NefrologiaSciEL

O uso de fitoterápicos orientais nas lesões renais: revisão integrativa

RESUMO As disfunções renais constituem um problema de saúde global com alta prevalência e custos com internações hospitalares. A fitoterapia chinesa possui tradição milenar na prevenção e tratamento dessas disfunções e conta com o incentivo da OMS às práticas integrativas e complementares; o número de pesquisas experimentais cresceu substancialmente. Esta revisão tem como objetivo levantar os estudos que relacionem o tratamento das disfunções renais com fórmulas fitoterápicas pertencentes à medicina tradicional chinesa; identificar os modelos de lesão renal adotados, as ervas e as doses empregadas, bem como a eficácia do tratamento. Os artigos foram selecionados nas bases Pubmed e Lilacs com os seguintes termos: medicina tradicional chinesa, rim, e erva, em modelos animais no período de 10 anos. Foram selecionados 12 estudos sendo que em 11 o fitoterápico conseguiu prevenir ou melhorar a lesão renal; em 6 estudos foram utilizadas fórmulas contendo associação de plantas; e em outros 6, o medicamento alopático foi o controle. Os modelos de lesão mais utilizados foram de nefrectomia e nefrotoxicidade enquanto a administração foi a via gavagem. A fitoterapia pode atuar como terapia complementar no tratamento das lesões renais, possui baixo custo e pode ser associado a intervenções alopáticas. Porém, é preciso conhecer profundamente os riscos, as possíveis interações, a toxicidade, e os mecanismos de ação, além dos possíveis efeitos adversos do uso dessas ervas

Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats

The frequent use of nonsteroidal anti-inflammatory drugs (NSAID) in combination with gentamicin poses the additional risk of nephrotoxic renal failure. Cyclooxygenase-1 (COX-1) is the main enzyme responsible for the synthesis of renal vasodilator prostaglandins, while COX-2 participates predominantly in the inflammatory process. Both are inhibited by non-selective NSAID such as indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer renal side effects than non-selective inhibitors. The objective of the present study was to determine whether the combined use of rofecoxib and gentamicin can prevent the increased renal injury caused by gentamicin and indomethacin. Male Wistar rats (250-300 g) were treated with gentamicin (100 mg/kg body weight, ip, N = 7), indomethacin (5 mg/kg, orally, N = 7), rofecoxib (1.4 mg/kg, orally, N = 7), gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively) or gentamicin + indomethacin (100 and 5 mg/kg, respectively, N = 8) for 5 days. Creatinine clearance and alpha-glutathione-S-transferase concentrations were used as markers of renal injury. Animals were anesthetized with ether and sacrificed for blood collection. The use of gentamicin plus indomethacin led to worsened renal function (0.199 ± 0.019 ml/min), as opposed to the absence of a nephrotoxic effect of rofecoxib when gentamicin plus rofexicob was used (0.242 ± 0.011 ml/min). These results indicate that COX-2-selective inhibitors can be used as an alternative treatment to conventional NSAID, especially in situations in which risk factors for nephrotoxicity are present