Scutellarin attenuates oxidative glutamate toxicity in PC12 cells.
The present study investigated the protective effects of the antioxidant scutellarin against oxidative toxicity induced by glutamate in PC12 cells. Vitamin E, a classical antioxidant was employed as a comparative agent. Incubation of PC12 cells with 10 mM glutamate resulted in significant cytotoxity as evaluated by the MTT and lactate dehydrogenase (LDH) assays, decreases of GSSG reductase activity, disturbance of the cell redox state as indicated by the GSH/GSSG ratio, and accumulation of intracellular reactive oxygen species (ROS) and lipid peroxidation products. Scutellarin at 0.1, 1 and 10 microM significantly protected against the cytoxicity and production of ROS and lipid peroxidation induced by glutamate. Scutellarin did not prevent the reduction of cellular GSH levels, but it up-regulated GSSG reductase activity, thus preventing an increase in cellular GSSG levels, and concomitantly improved the cell redox status. Our data also show that the protective effects of scutellarin against glutamate-induced oxidative toxicity are more potent than that of vitamin E. These results demonstrate that scutellarin can protect PC12 cells from oxidative glutamate toxicity by scavenging ROS, inhibiting lipid peroxidation and improving the cell redox status, and may reduce the cellular damage in pathological conditions associated with excessive glutamate release.
Hong
Hao
H
Department of Pharmacology, China Pharmaceutical University, Nanjing, The People's Republic of China. haohongchina@hotmail.com
Liu
Guo-Qing
GQ
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D047310:Apigenin; D017209:Apoptosis / Q000187:drug effects; D019659:Asteraceae; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005965:Glucuronates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019803:Glutathione Disulfide / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects / Q000201:enzymology; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000975:Antioxidants; D005419:Flavonoids; D005965:Glucuronates; D010936:Plant Extracts; D020011:Protective Agents; D014810:Vitamin E; C484876:scutellarin; D047310:Apigenin; D019803:Glutathione Disulfide