| ObjectiveCadmium ( Cd) is a kind of toxic heavy metal that seriously contaminates the environment and mainly comes from the industrial products. Chronic exposure to Cd mainly causes the renal proximal tubule damage, which represents that the excretion of proteinuria, glucosuria, aminoaciduria, enzymaticuria and urinary cadmium increase. Cd2+ can combine to the acceptors or protein of cy-tomembrane result in affecting cellular functions and perturbing signal transductions. The concentration increasing of intracellular calcium by Cd may abnormally activate calmodulin ( CaM ) result in other enzyme ( Na+ - K+ - ATPase, Ca2+ -ATPase, Protein kinase C) activated. When Ca2+ is presence, CaM inhibitors, such as Chlorpromazine (CPZ) , can tightly combine to CaM result in blocking the interaction of Cd2+ and CaM, and inhibiting enzymes activated by CaM. The calcium channel blockers Verapamil (Ver) inhibit the uptake of Ca2 + , and if dose increased, it can inhibit the release of intracellular calcium. Ver can prevent smooth muscle convulsion and cell damage by intracellular calcium overloading. The objective of the present study was to observe the effect of different dosage Cd doing harm to kidney in Wistar rats and to determine the toxic dosage of Cd. Meanwhile we have a pretreatment with CPZ and Ver so that to discuss the preventive effect on CPZ and Ver mitigating neprotoxicity, which provide the academic base for precaution and healing, when Cd poisoning occurs.Method64 Wistar rats obtained from the Laboratory Animal Center of Chinese Medicine University, weighing (150 ±10) gram. The rats were housed at (22 ±2) Celsius degree with alternating light and dark. After an acclimation period of a week, the Experiment started in two parts. At first, to study the dose - response relationship so as to determine the toxic dosage of Cd. 32 rats were randomly assigned into 4 groups, which were respectively described as control group, 3 μmol/kg, 5 μmol/kg and 7 μmol/kg Cd group. Every group contains 4 female and 4 male rats. During the experiment rats of control group were injected sub-cutaneously ( sc) with 2 ml/kg body weight 0. 9% saline, 5 times per week, for up to 6 weeks. The second part experiment was pretreatment with CPZ and Ver so that to discuss the preventive effect of them. 32 rats were randomly assigned into 4 groups, which were respectively described as control group, 7 μmol/kg Cd group, CPZ and Ver pretreatment group. Every group contains 4 female and 4 male rats. The Cd given alone group rats were sc injected with 7 μmol CdCl2/ kg body weight/day. The CPZ and Ver pretreatment group rats were intraperito-neally (ip) injected with 5 mg CPZ/kg body weight/day, 4 mg Ver/kg body weight/day, respectively, one hour later sc administrated with 7 μmol CdCl2/kg body weight/day. During the experiment rats of control group were injected sub-cutaneously with 2 ml/kg body weight 0.9% saline, 5 times per week, for up to 6 weeks. After intoxicated 24 hours, rats of all sorts were transfer to the metabolic cages to collect the urine. The rats were killed by aether and kidneys were immediately removed. During the experiment process all operations were run carefully under the iced condition.Then the renal cortexes were homogenated. Cd concentrations in renal cortex and urinary were determined by Atomic Absorbance Spectrophotometer. Urinary LDH activity was measured by the colorimetry with lactic acid as the matrix. Urinary NAG activity was measured by the p - nitrohydroxybenzene colorimetry. Urinary ALP activity was measured by Jin's method. Urinary protein contents were measured by Coomassie brilliant blue method. Urinary creatinine lev-el was measured by picric acid colorimetry. PKC activity was measured by the method of Takai et al. Na+ - K+ - ATPase and Ca2+ - ATPase activities were measured according to the method of Shen et al.ResultsAccompanied with increasing treated Cd dosage, the activities of urinary LDH, NAG and ALP, the contents of urinary protein and Cd, the activities of Na+ - K+ - ATPase and Ca2+ - ATPase in renal cortexes in various treated groups went up. Compared to the control, the activities of Na+ - K+ - ATPase and Ca 2+ - ATPase had a little increase in the 5 μmol/kg Cd groups, but no significantly. However, the activities of Na+ -K+ -ATPase and Ca2+ -ATPase in the 7 μmol/kg Cd group went up significantly compared to the control. Therefore, we took 7 μmol/kg as the toxic dosage of Cd.In the second part experiment, urinary LDH, NAG and ALP activities, urinary protein content and Cd concentrations in renal cortex and urinary in Cd a-lone group were significantly higher than that of control group. As compared with Cd alone group, urinary LDH and NAG activities, urinary protein content and u-rinary Cd concentrations significantly decreased in CPZ pretreatment group. Ver pretreatment significantly suppressed the rise in urinary NAG and ALP activities, urinary protein content and urinary Cd concentrations. However, there is no variance on the Cd concentrations in renal cortex between CPZ and Ver pretreatment groups.Na+ -K+ -ATPase and Ca2+ - ATPase activities in renal cortex of Cd a-lone group were significantly higher than that of control group. As compared with Cd alone group, Ca2+ - ATPase activity significantly decreased in CPZ pretreatment group, but Na+ -K+ -ATPase activity did not significantly change. Na + -K+ -ATPase and Ca2+ - ATPase activities were lower than that of Cd alone group.Protein kinase C activities in the cytomembrane and cytoplasm of renal cortex of Cd alone group were significantly higher than that of control group. As compared with Cd alone group, PKC activities in the cytomembrane and cyto-...
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