Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, 23119, Elazig, Turkey.
Biol Trace Elem Res. 2012 Dec;150(1-3):291-6. doi: 10.1007/s12011-012-9475-9. Epub 2012 Jul 13.
The objective of this experiment was to investigate the effects of supplemental chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB p65) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in diabetic rat brain. Nondiabetic (n = 45) and diabetic (n = 45) male Wistar rats were either not supplemented or supplemented with CrPic or CrHis via drinking water to consume 8 μg elemental chromium (Cr) per day for 12 weeks. Diabetes was induced by streptozotocin injection (40 mg/kg i.p., for 2 weeks) and maintained by high-fat feeding (40 %). Diabetes was associated with increases in cerebral NF-κB and 4-hydroxynonenal (4-HNE) protein adducts and decreased in cerebral nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα) and Nrf2 levels. Both Cr chelates were effective to decrease levels of NF-κB and 4-HNE protein adducts and to increase levels of IκBα and Nrf2 in the brain of diabetic rats. However, responses of these increases and decreases were more notable when Cr was supplemented as CrHis than as CrPic. In conclusion, Cr may play a protective role in cerebral antioxidant defense system in diabetic subjects via the Nrf2 pathway by reducing inflammation through NF-κB p65 inhibition. Histidinate form of Cr was superior to picolinate form of Cr in reducing NF-κB expression and increasing Nrf2 expression in the brain of diabetic rats.
本实验旨在研究补充吡啶甲酸铬(CrPic)和组氨酸铬(CrHis)对糖尿病大鼠大脑核因子-κB(NF-κB p65)和核因子(红系衍生 2)样 2(Nrf2)信号通路的影响。非糖尿病(n = 45)和糖尿病(n = 45)雄性 Wistar 大鼠通过饮用水补充 CrPic 或 CrHis,每天消耗 8μg 元素铬(Cr),持续 12 周。糖尿病通过链脲佐菌素注射(40mg/kg,腹腔内,持续 2 周)诱导,并通过高脂肪喂养(40%)维持。糖尿病与大脑 NF-κB 和 4-羟基壬烯醛(4-HNE)蛋白加合物的增加以及大脑κ轻链增强子核因子抑制物,α(IκBα)和 Nrf2 水平的降低有关。两种铬螯合物均能有效降低糖尿病大鼠大脑中 NF-κB 和 4-HNE 蛋白加合物的水平,并增加 IκBα 和 Nrf2 的水平。然而,当 Cr 以 CrHis 的形式而不是以 CrPic 的形式补充时,这些增加和减少的反应更为显著。总之,Cr 通过抑制 NF-κB p65 可能通过 Nrf2 途径在糖尿病患者的大脑抗氧化防御系统中发挥保护作用。在糖尿病大鼠的大脑中,组氨酸铬的形式比吡啶甲酸铬更能降低 NF-κB 的表达,增加 Nrf2 的表达。