Fernandes Marcelo Bandeira, Caldas Heloisa Cristina, Toloni Lais Dumbra, Baptista Maria Alice Sperto Ferreira, Fernandes Ida Maria Maximina, Abbud-Filho Mario
From the Laboratory of Immunology and Experimental Transplantation-LITEX, Sao Jose Rio Preto, SP, Brazil.
Exp Clin Transplant. 2014 Dec;12(6):522-7.
Calcineurin inhibitors are effective immunosuppressive agents, but associated adverse effects such as nephrotoxicity may limit efficacy. Dietary fish oil may minimize nephrotoxicity caused by long-term use of calcineurin inhibitors. The purpose of the present study was to evaluate the effects of omega-3 fatty acids on calcineurin inhibitor nephrotoxicity in rats that had normal kidney function or chronic kidney failure.
Rats that had normal kidney function or chronic renal failure that was induced by mass reduction surgery were treated with tacrolimus without or with fish oil, fish oil alone, or olive oil. Kidney function and histology were evaluated after 14 days.
Mean body weight loss, serum creatinine, change in serum creatinine, and rate of decrease in creatinine clearance were greater in normal rats that received than did not receive tacrolimus. Tacrolimus nephrotoxicity was greater in rats that had chronic renal failure than normal kidney function, but the mean change in serum creatinine was significantly lower in rats with chronic renal failure that were treated with tacrolimus and fish oil than tacrolimus alone. Fish oil supplementation was associated with fewer abnormal histopathologic lesions in the kidneys of tacrolimustreated rats that had normal kidney function or chronic renal failure (not signifant).
Fish oil may be protective against the development of kidney dysfunction and histopathologic changes in rats treated with tacrolimus.
钙调神经磷酸酶抑制剂是有效的免疫抑制剂,但诸如肾毒性等相关不良反应可能会限制其疗效。膳食鱼油可能会使长期使用钙调神经磷酸酶抑制剂所导致的肾毒性降至最低。本研究的目的是评估ω-3脂肪酸对肾功能正常或患有慢性肾衰竭的大鼠的钙调神经磷酸酶抑制剂肾毒性的影响。
对肾功能正常或因减体手术诱发慢性肾衰竭的大鼠,分别给予他克莫司(单独使用或与鱼油联用)、单独使用鱼油或橄榄油进行治疗。14天后评估肾功能和组织学情况。
接受他克莫司治疗的正常大鼠的平均体重减轻、血清肌酐、血清肌酐变化及肌酐清除率下降速率均高于未接受他克莫司治疗的大鼠。他克莫司对慢性肾衰竭大鼠的肾毒性大于对肾功能正常大鼠的肾毒性,但在接受他克莫司和鱼油联合治疗的慢性肾衰竭大鼠中,血清肌酐的平均变化显著低于单独使用他克莫司治疗的大鼠。在接受他克莫司治疗且肾功能正常或患有慢性肾衰竭的大鼠中,补充鱼油与较少的肾脏异常组织病理学损伤相关(无显著差异)。
鱼油可能对接受他克莫司治疗的大鼠的肾功能障碍和组织病理学变化的发展具有保护作用。