De Craemer D, Pauwels M, Van den Branden C
Menselijke Anatomie & Embryologie, Vrije Universiteit Brussel, Belgium.
Lipids. 1996 Nov;31(11):1157-61. doi: 10.1007/BF02524290.
NMRI mice were fed diets supplemented with 0.05, 0.2, or 2% (w/w) docosahexaenoic acid (DHA), a polyunsaturated fatty acid present in fish oil, for 3 d, 3 wk, or 3 mon. The doses of DHA were chosen to supply the mice with concentrations of DHA which approximate those that have been reported to be beneficial to patients with peroxisomal disease. Diets containing 0.05 or 0.2% DHA did not change hepatic, myocardial, and renal catalase (EC 1.11.1.6) activity except for a slight but significant increase (to 120%) in myocardial catalase activity in mice treated with the 0.05% DHA diet for 3 mon. A diet with 2% DHA induced myocardial catalase activity to 150% after both 3 d and 3 wk of administration. In the liver of mice fed this diet for 3 wk, hepatic catalase activity was increased to 140% while no induction of palmitoyl-CoA oxidase (EC 1.3.99.3), urate oxidase (EC 1.7.3.3), and L-alpha-hydroxyisovalerate oxidase (EC 1.1.3.a) was observed. With the light microscope, no changes in peroxisomal morphology were visually evaluated in catalase stained sections of liver, myocardium, and kidney of mice fed either diet. Our results show that in healthy mice a low dietary DHA dose (< 0.2%; this corresponds to a dose prescribed to peroxisomal patients) has no effect on several hepatic peroxisomal H2O2-producing enzymes, including the rate-limiting enzyme of the peroxisomal fatty acid beta-oxidation. This may indicate that such a DHA dose will not add a strong load on the often disturbed fatty acid metabolism in the liver of patients with peroxisomal disorders.
将NMRI小鼠喂食添加了0.05%、0.2%或2%(w/w)二十二碳六烯酸(DHA,一种存在于鱼油中的多不饱和脂肪酸)的饲料,持续3天、3周或3个月。选择这些DHA剂量是为了给小鼠提供与据报道对过氧化物酶体疾病患者有益的浓度相近的DHA。含0.05%或0.2% DHA的饲料对肝脏、心肌和肾脏过氧化氢酶(EC 1.11.1.6)活性没有影响,除了用0.05% DHA饲料处理3个月的小鼠心肌过氧化氢酶活性有轻微但显著的增加(至120%)。给予含2% DHA的饲料3天和3周后,心肌过氧化氢酶活性诱导至150%。在喂食该饲料3周的小鼠肝脏中,肝脏过氧化氢酶活性增加至140%,而未观察到棕榈酰辅酶A氧化酶(EC 1.3.99.3)、尿酸氧化酶(EC 1.7.3.3)和L-α-羟基异戊酸氧化酶(EC 1.1.3.a)的诱导。用光学显微镜观察,在喂食任何一种饲料的小鼠肝脏、心肌和肾脏的过氧化氢酶染色切片中,均未肉眼评估到过氧化物酶体形态的变化。我们的结果表明,在健康小鼠中,低剂量的膳食DHA(<0.2%;这相当于给过氧化物酶体疾病患者规定的剂量)对几种肝脏过氧化物酶体产生H2O2的酶没有影响,包括过氧化物酶体脂肪酸β-氧化的限速酶。这可能表明这样的DHA剂量不会给过氧化物酶体疾病患者肝脏中经常紊乱的脂肪酸代谢增加很大负担。