Vermilion Paste Renal Toxicity And Mechanism Study

Objective:Chronic skin ulcers is a common recurrent disease. To study the toxic effects on the kidney, Sensitive and specific biomarkers for early kidney tubular injury, mechanism of toxicity of Zhuhong Ointment containing mercury which is an external preparation of traditional Chinese medicine.Methods:Firstly, Wistar rats (n=200) were randomly divided into the high dose group, moderate group, low dose group, Vaseline group and impairment control group. Apply Zhuhong Ointment on the damaged skin every day for 4 weeks. Took mercury and NAG contents in the urine as monitoring indexes, and observed the pathological morphology changes of kidney after administration for 2 weeks, 4weeks, and recovery 2 weeks,4 weeks.Secondly, SD rats (n=80) were randomly divided into different dose groups, 1218.56 mg/kg (A group),609.28 mg/kg (B group),304.64 mg/kg (C group),152.32 mg/kg (D group),76.16 mg/kg (E group), Vaseline group, ulcer model group and impairment control group. Apply Zhuhong Ointment on ulcers, which were established on the absence skin, foreign body and staphylococcal infection, every day for 2 weeks. Body weight was recorded once every week. Tested Urine pH and compared NAG with RBP after administration for 7 days and 14 days.Thirdly, Measured the content of malondiadehyde(MDA), total anti-oxidation capability (T-AOC)superoxide dismutase(SOD), glutathione peroxidase(GSH-PX), glutathione(GSH), metallothionein(MT) and Na+-K+-ATPase to explore the mechanism of toxicity of Zhuhong Ointment.Results:1. Toxic effects on the kidneyThe urine mercury levels of low dose and high dose group were remarkably higher than impairment control group. NAG results appeared there was no significant difference between Zhuhong Ointment groups and the impairment control group. Administration for 2 weeks, Morphological changes in the rat kidney, the renal tubular epithelial cells often cloudy swelling and fatty change, in moderate group was mild, while the lesions were not significantly increased after administration for 4 weeks.2. Sensitive and specific biomarkers for early kidney tubular injuryThe pH of urine samples did not meet the conditions for measurement of p2-MG. After treatment for 7 d, compared with ulcer modle group, urinary NAG and RBP content in every dose group had no significant difference except A group. After treatment for two weeks, compared with ulcer modle group, the levels of RBP in A, B, C and D group increased, while the levels of NAG increased only in A group.3. Mechanism of toxicityCompared with ulcer modle group, the kidney coefficient increased in every dose group. MDA content in A group increased greatly. The level of T-AOC increased in three groups of A, B and C. The level of T-SOD increased in E group, while it dropped down greatly in A group. The level of GSH-PX increased in three groups of A, B and C. the content of GSH increased in every dose group. The level of MT increased in four groups of A, B, C and D. The level of Na+-K+-ATPase dropped down obviously in A group, while it increased in Vaseline group and three groups of C, D and E.Conclusion:1. Administration of Zhuhong Ointment for a long time can cause renal tubular injury.9.52mg/kg of crude drug was the safe dose relatively after treatment for four weeks.2. As a specific biomarker for early kidney tubular injury, urine RBP appeared earlier more sensitive than urine NAG.3. The mechanism of toxicity may be related to oxidant injury, MT and Na+-K+-ATPase.