Valentovic Monica A, Alejandro Napoleon, Betts Carpenter A, Brown Patrick I, Ramos Kenneth
Department of Pharmacology, Joan C. Edwards School Of Medicine, Marshall University1532 Spring Valley Drive, Huntington, WV 25704-9388, USA.
Toxicol Lett. 2006 Jul 14;164(3):214-20. doi: 10.1016/j.toxlet.2005.12.009. Epub 2006 Feb 7.
Information is lacking regarding the biological response to environmental chemicals in the context of pre-existing disease. Benzo(alpha)pyrene (BaP), a polycyclic aromatic hydrocarbon, is a byproduct of combustion that causes renal injury and elicits a nephropathic response. This study evaluated the nephrotoxicity of BaP in normoglycemic and diabetic rats. Female Sprague Dawley rats were divided into four groups: normoglycemic-vehicle (NV), normoglycemic-BaP (N-BaP), diabetic-vehicle (DV) and diabetic-BaP (D-BaP). Diabetes was induced by intraperitoneal (ip) injection of streptozotocin (60 mg/kg, 1 ml/kg). Rats were injected (ip) with vehicle or 10 mg/kg BaP (1 ml/kg) once per week for 5 weeks. Urinary protein and albumin, plasma creatinine and light microscopy were performed to assess the effects of BaP on kidney function. Diabetes was confirmed by plasma glucose levels >400 mg/dl in the DV and D-BaP groups. BaP increased kidney weight and blood urea nitrogen (BUN) levels in the D-BaP relative to the DV group. No change in BUN was observed following 5 weeks of BaP treatment in the normoglycemic animals, however, kidney weight was increased (p=0.013) in the N-BaP relative to the NV animals. STZ diabetes increased susceptibility to BaP mediated renal damage following repeated treatment for 5 weeks when compared to age matched normoglycemic rats.
关于在已有疾病背景下对环境化学物质的生物学反应的信息尚缺。苯并(α)芘(BaP)是一种多环芳烃,是燃烧的副产物,可导致肾损伤并引发肾病反应。本研究评估了BaP在血糖正常和糖尿病大鼠中的肾毒性。将雌性Sprague Dawley大鼠分为四组:血糖正常-溶剂对照组(NV)、血糖正常-BaP组(N-BaP)、糖尿病-溶剂对照组(DV)和糖尿病-BaP组(D-BaP)。通过腹腔注射链脲佐菌素(60 mg/kg,1 ml/kg)诱导糖尿病。大鼠每周腹腔注射一次溶剂或10 mg/kg BaP(1 ml/kg),共5周。检测尿蛋白和白蛋白、血浆肌酐并进行光学显微镜检查,以评估BaP对肾功能的影响。DV组和D-BaP组血浆葡萄糖水平>400 mg/dl证实糖尿病。与DV组相比,D-BaP组中BaP使肾脏重量和血尿素氮(BUN)水平增加。在血糖正常的动物中,BaP治疗5周后未观察到BUN变化,然而,与NV组动物相比,N-BaP组肾脏重量增加(p = 0.013)。与年龄匹配的血糖正常大鼠相比,链脲佐菌素诱导的糖尿病在重复治疗5周后增加了对BaP介导的肾损伤的易感性。