摘要:
邻苯二甲酸二异壬酯是一种新型替代增塑剂,对其毒性研究已受到广泛关注。为探究邻苯二甲酸二异壬酯对肾组织的氧化损伤作用,将昆明小鼠随机分为5组,包括1个阴性对照组、4个邻苯二甲酸二异壬酯染毒组,按0.5、5、50和500 mg·kg-1四个剂量水平灌胃染毒14天。制备小鼠肾组织切片进行病理学观察,以肾组织匀浆测定活性氧(reactive oxygen species,ROS)、还原型谷胱甘肽(glutathione,GSH)、丙二醛(malondialdehyde,MDA)和8-羟基脱氧鸟苷(8-hydroxy-2-deoxyguanosine,8-OHd G)的含量,以肾组织细胞悬液测定DNA-蛋白质交联(DNA-protein Crosslink,DPC)系数。随着邻苯二甲酸二异壬酯染毒剂量的升高,小鼠肾组织的损伤程度加重,ROS、MDA、8-OHd G含量和DPC系数逐渐上升,GSH含量逐渐降低,各指标均呈一定剂量-效应关系。染毒剂量为5 mg·kg-1时,ROS、DPC系数差异有统计学意义(P<0.05,P<0.01);染毒剂量为50 mg·kg-1和500 mg·kg-1时,ROS、GSH、8-OHd G、MDA含量和DPC系数差异均有统计学意义(P<0.05,P<0.01)。结果表明较高剂量(≥ 50 mg·kg-1)邻苯二甲酸二异壬酯可造成小鼠肾组织氧化损伤。
Abstract:
Diisononyl phthalate (DINP) has been widely used in polyvinyl chloride (PVC) products and is ubiquitous as a substitute; however, its toxicity due to exposure remains to be determined. This study investigated the oxidative damage induced by diisononyl phthalate on mouse kidney tissue. Kunming mice were randomly grouped into five groups and orally administered with drugs daily for fourteen days; the groups included one solvent control group, four diisononyl phthalate groups, the exposure doses of disononyl phthalate groups were 0.5, 5, 50 and 500mg·kg-1 respectively. Kidney tissue sections were isolated and stained for pathological observations under micro-scope. Contents of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHd G) in kidney tissue homogenates, and DNA-protein crosslink (DPC) coefficients in the kidney cell suspensions were measured. Results showed that kidney tissue injury was severed gradually with the increase of diisononyl phthalate exposure concentration, contents of ROS, MDA, 8-OHd G and DPC coefficients increased gradually in a dose-dependent manner, whereas GSH content decreased accordingly. In the 5 mg·kg-1 exposure group, ROS contents and DPC coefficients were higher compare with the control group (P<0.05, P<0.01). In the high-dose exposure groups (50 and 500 mg·kg-1), there were significant differences in levels of each biomarker compare with the control group (P<0.05, P<0.01). Data suggest that diisononyl phthalate at certain doses (≥ 50 mg·kg-1) can induce damage in mice kidney, and oxidative damage is involved in diisononyl phthalate-induced kidney toxicity.
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