Roy D, Pathak D N, Singh R
J Neurochem. 1984 Mar;42(3):628-33. doi: 10.1111/j.1471-4159.1984.tb02728.x.
In this work, the effect of chronic intraperitoneal administration of chlorpromazine (5 and 10 mg/kg) on the antioxidant enzymes superoxide dismutase (SOD), catalase (CA), glutathione reductase (GR), and glutathione peroxidase (GP); lipid peroxidation; and lipofuscin accumulation in the brains of rats ages 6, 9, and 12 months was studied. Chlorpromazine increased the activities of SOD, GR, and GP in particulate fraction from cerebrum, cerebellum, and brain stem in a dose-dependent manner. While GR and SOD associated with soluble fraction increased, GP associated with soluble fraction was not affected. CA did not change after chlorpromazine administration in any regions of the brain of rats from all age groups. Chlorpromazine, thus, had a somewhat different action on antioxidant enzymes in different subcellular fractions. Chlorpromazine inhibited lipid peroxidation, both in vivo and in vitro, and it also inhibited accumulation of lipid peroxidation fluorescent products (lipofuscin), which was studied histochemically and biochemically as well. The data indicate that chlorpromazine inhibition of lipid peroxidation and of accumulation of lipofuscin can result from elevation of the activity of brain antioxidant enzymes.
在本研究中，我们探究了长期腹腔注射氯丙嗪（5毫克/千克和10毫克/千克）对6个月、9个月和12个月龄大鼠大脑中抗氧化酶超氧化物歧化酶（SOD）、过氧化氢酶（CA）、谷胱甘肽还原酶（GR）和谷胱甘肽过氧化物酶（GP）的影响；脂质过氧化作用；以及脂褐素积累情况。氯丙嗪以剂量依赖的方式增加了大脑、小脑和脑干微粒体部分中SOD、GR和GP的活性。虽然与可溶性部分相关的GR和SOD增加，但与可溶性部分相关的GP未受影响。在所有年龄组大鼠大脑的任何区域，氯丙嗪给药后CA均未发生变化。因此，氯丙嗪对不同亚细胞部分的抗氧化酶作用有所不同。氯丙嗪在体内和体外均抑制脂质过氧化作用，并且还抑制脂质过氧化荧光产物（脂褐素）的积累，我们通过组织化学和生物化学方法对此进行了研究。数据表明，氯丙嗪对脂质过氧化作用和脂褐素积累的抑制可能是由于大脑抗氧化酶活性的提高所致。
