RESUMO
The polyuric syndrome that develops as a consequence of chronic administration of lithium salts is most frequent and often causes complication in the treatment of manic depressive disease with the administration of drugs. It is known that kidneys play an essential role in systematic depositing of toxic metals. The purpose of this study was not only the determination of dose-dependent lithium concentration in serum and urine but also an estimation of sensitive biochemical indicators of nephrotoxicity detectable at an early stage after the administration of lithium carbonate to rats. Animals were given orally lithium salt to female Wistar rats at the dose of 10 and 20mg Li/kg daily during 5 weeks. In the urine diuresis protein concentration, copper, zinc, lithium and N-acetyl-beta-glucoaminidase (NAG) activity were determined. In the serum also lithium, copper and zinc were analyzed. The results of the experiments indicate that the changes in urinary concentrations of essential copper, proteins, NAG activity and diuresis were observed when the concentration of lithium was ca. 9.79+/-1.68 mmol Li/L and in serum it corresponded to 0.3+/-0.06 mmol Li/L. These values corresponded to total doses of 150 mg Li/kg body weight administered to rats. In summary the increase of copper concentration, diuresis and urinary concentrations of protein and the NAG activity may be interpreted as a general metabolic response of kidneys induced by lithium detectable as an earlier indicator of nephrotoxicity. Therefore, regular determinations of lithium concentrations in serum of patients are important tools in the prevention of intoxication.
Assuntos
Injúria Renal Aguda/metabolismo , Lítio/intoxicação , Oligoelementos/metabolismo , Acetilglucosamina/urina , Injúria Renal Aguda/induzido quimicamente , Animais , Cobre/urina , Diurese/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Lítio/sangue , Lítio/urina , Proteinúria/induzido quimicamente , Ratos , Ratos Wistar , Oligoelementos/urina , Urodinâmica/efeitos dos fármacosRESUMO
The kidney is the appropriate critical organ for indicating chronic exposure to chromium compounds. The present work investigates the effect of dose-dependent hexavalent chromium concentration in various tissues of rats, the disturbances in metabolism of zinc and copper in liver and kidney, and histopathological changes in kidneys. White Wistar rats were used. Animals were injected intraperitoneally at a dose of 0.5 and 5 mg Cr/kg as K2CrO4. The animals were sacrificed after single and repeated doses at 24 h after the last injection. Disturbances in the metabolism of zinc and copper in the kidney of rats occur when the concentration of chromium in this organ attains about 30 microg Cr/g. An increase in urinary output of these essential metals is a more sensitive indicator of nephrotoxicity than ultrastructural damage of kidney.