Villa P, Cova D, De Francesco L, Guaitani A, Palladini G, Perego R
C.N.R. (National Research Council) Center of Cytopharmacology, Department of Pharmacology, Milan, Italy.
Toxicology. 1992;73(2):179-89. doi: 10.1016/0300-483x(92)90101-j.
Primary cultures of rat hepatocytes were used to study the effects of the flavonoids diosmin and its main metabolite diosmetin on the cell membrane damage caused by erythromycin estolate (EE) and oxidative stress caused by tert-butylhydroperoxide (TBHP). The damage was evaluated by the leakage of intracellular enzymes lactate dehydrogenase, aspartate-aminotransferase and the residual cell content of a lysosomal marker acid phosphatase (AP). After treating the cells for 40 h with diosmetin EE induced less enzyme leakage. The content of AP was kept higher by diosmetin pretreatment after 6 h exposure to EE. Diosmin at the same concentrations had barely any effect. Diosmetin, but not diosmin, also protected against TBHP toxicity and this was related to lower lipid peroxidation and higher glutathione content caused by pretreatment with the flavonoid. When the cells were treated simultaneously with TBHP and diosmetin after 21 h of culture, the protection by the flavonoid was even higher. In fact the antioxidant activity of diosmetin was considerably greater than that of diosmin. After 40 h exposure to both flavonoids diosmin but not diosmetin was detectable in the cell membrane fraction, suggesting that the latter's protective effect is associated with its metabolites.
大鼠肝细胞原代培养物被用于研究黄酮类化合物地奥司明及其主要代谢产物地奥司亭对依托红霉素（EE）引起的细胞膜损伤和叔丁基过氧化氢（TBHP）引起的氧化应激的影响。通过细胞内酶乳酸脱氢酶、天冬氨酸转氨酶的泄漏以及溶酶体标志物酸性磷酸酶（AP）的残余细胞含量来评估损伤。用地奥司亭处理细胞40小时后，EE诱导的酶泄漏减少。在暴露于EE 6小时后，地奥司亭预处理使AP含量保持较高水平。相同浓度的地奥司明几乎没有任何作用。地奥司亭而非地奥司明也能保护细胞免受TBHP毒性，这与黄酮类化合物预处理导致的较低脂质过氧化和较高谷胱甘肽含量有关。当细胞在培养21小时后同时用TBHP和地奥司亭处理时，黄酮类化合物的保护作用甚至更高。事实上，地奥司亭的抗氧化活性明显大于地奥司明。在暴露于两种黄酮类化合物40小时后，在地奥司明但在地奥司亭的细胞膜部分中未检测到，这表明后者的保护作用与其代谢产物有关。
