Aydın A Fatih, Çoban Jale, Doğan-Ekici Işın, Betül-Kalaz Esra, Doğru-Abbasoğlu Semra, Uysal Müjdat
Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Department of Biochemistry, Yeditepe University Medical Faculty, Istanbul, Turkey.
Metab Brain Dis. 2016 Apr;31(2):337-45. doi: 10.1007/s11011-015-9755-0. Epub 2015 Oct 31.
D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; β-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats.
D-半乳糖（GAL）已被用作脑衰老和抗衰老研究的动物模型。GAL可刺激包括脑在内的多个组织中的氧化应激。肌肽（CAR；β-丙氨酰-L-组氨酸）和牛磺酸（TAU；2-氨基乙磺酸）具有抗氧化特性。CAR和TAU具有抗衰老和神经保护作用。我们研究了补充CAR和TAU对GAL处理大鼠氧化应激和脑损伤的影响。大鼠单独接受GAL（300mg/kg；皮下注射；每周5天）或与CAR（250mg/kg/天；腹腔注射；每周5天）或TAU（2.5%w/w；添加到大鼠饲料中）一起处理2个月。测定脑丙二醛（MDA）、蛋白质羰基（PC）和谷胱甘肽（GSH）水平以及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、谷胱甘肽转移酶（GST）和乙酰胆碱酯酶（AChE）活性。还通过免疫组织化学评估脑中B细胞淋巴瘤-2（Bcl-2）、Bax和半胱天冬酶-3的表达。GAL处理增加了脑MDA和PC水平以及AChE活性。它显著降低了脑GSH水平、SOD和GSH-Px活性，但未降低GST活性。GAL处理导致组织病理学变化并增加细胞凋亡。CAR和TAU显著降低了GAL处理大鼠的脑AChE活性、MDA和PC水平，并提高了GSH水平。CAR而非TAU显著提高了SOD和GSH-Px的低活性。CAR和TAU均减少了GAL处理大鼠脑中的细胞凋亡并改善了组织病理学结果。我们的结果表明，CAR和TAU可能有效地预防GAL处理大鼠脑中氧化应激、细胞凋亡和组织病理学恶化的发生。
