al-Bayati M A, Giri S N, Raabe O G, Rosenblatt L S, Shifrine M
Institute for Environmental Health Research, University of California, Davis 95616.
J Environ Pathol Toxicol Oncol. 1989 Dec;9(5-6):435-55.
Vanadate at a dosage level of 0.9 mg V/kg per day produced acute toxic signs in rats when injected subcutaneously for 16 days. These signs were weakness, loss of appetite, dehydration, significant reduction in body weight, nose bleeding, and death. The pathological and biochemical changes were most severe in kidney tissue. The kidney lesions were bilateral and multifocal. At two days, degenerative and necrotic changes of the tubular and glomerular epithelium, thickening of glomerular membrane, vascular congestion, and edema were observed. At five days, proliferation of tubular epithelial and interstitial cells was observed. At 12 days, the cellular proliferation in both cortex and medulla was significantly greater. Fibrosis was observed at glomerular tuft, preglomeruli, pretubules, and interstitium (cortex and medulla). At 25 days, the collagen deposition reached the highest level in all regions, cellular proliferation decreased, and thickening of the arteriolar wall became prominent. The renal lesions were coupled with changes in the levels of protein, RNA, DNA, and hydroxyproline. At 40 days, the kidney showed signs of recovery. Blood urea nitrogen levels were significantly elevated at 2-25 days post-treatment. Stained tissue sections from liver, lung, heart, spleen, thymus, lymph nodes, testes, and adrenal glands of the treated rats were examined microscopically and appeared normal. Biochemically, significant changes (p less than .05) in protein, RNA, DNA, and hydroxyproline were also observed in these organs. At lower dosage (0.6 mg V/kg per day for 16 days), similar but less severe pathological and biochemical changes in kidneys and other organs were observed. At 0.3 mg V/kg per day for 16 days, the changes in the tissues were detected only at the biochemical level. These results indicate that the toxic effects of vanadium are cumulative and that vanadium-produced fibrosis in tissues is dose-dependent.
每天以0.9毫克钒/千克的剂量皮下注射16天，钒酸盐会使大鼠出现急性中毒症状。这些症状包括虚弱、食欲不振、脱水、体重显著减轻、鼻出血和死亡。病理和生化变化在肾组织中最为严重。肾脏病变为双侧性且多灶性。在第2天，观察到肾小管和肾小球上皮细胞的变性和坏死变化、肾小球膜增厚、血管充血和水肿。在第5天，观察到肾小管上皮细胞和间质细胞的增殖。在第12天，皮质和髓质中的细胞增殖明显增加。在肾小球丛、肾小球前、肾小管前和间质（皮质和髓质）观察到纤维化。在第25天，所有区域的胶原沉积达到最高水平，细胞增殖减少，小动脉壁增厚变得明显。肾脏病变与蛋白质、RNA、DNA和羟脯氨酸水平的变化相关。在治疗后第2 - 25天，血尿素氮水平显著升高。对经处理大鼠的肝脏、肺、心脏、脾脏、胸腺、淋巴结、睾丸和肾上腺的染色组织切片进行显微镜检查，结果显示正常。在生化方面，这些器官中蛋白质、RNA、DNA和羟脯氨酸也出现了显著变化（p小于0.05）。在较低剂量（每天0.6毫克钒/千克，持续16天）下，在肾脏和其他器官中观察到了类似但不太严重的病理和生化变化。在每天0.3毫克钒/千克，持续16天的情况下，仅在生化水平检测到组织变化。这些结果表明钒的毒性作用是累积性的，并且钒在组织中产生的纤维化是剂量依赖性的。
