title: KIOM-4 Protects against Oxidative Stress-Induced Mitochondrial Damage in Pancreatic β-cells via Its Antioxidant Effects.
abstract: The protective effect of KIOM-4, a mixture of plant extracts, was examined against streptozotocin (STZ)-induced mitochondrial oxidative stress in rat pancreatic β-cells (RINm5F). KIOM-4 scavenged superoxide and hydroxyl radicals generated by xanthine/xanthine oxidase and Fenton reaction (FeSO(4)/H(2)O(2)), respectively, in a cell-free chemical system. In addition, a marked increase in mitochondrial reactive oxygen species (ROS) was observed in STZ-induced diabetic cells; this increase was attenuated by KIOM-4 treatment. Mitochondrial manganese superoxide dismutase (Mn SOD) activity and protein expression were down-regulated by STZ treatment and up-regulated by KIOM-4 treatment. In addition, NF-E2 related factor 2 (Nrf2), a transcription factor for Mn SOD, was up-regulated by KIOM-4. KIOM-4 prevented STZ-induced mitochondrial lipid peroxidation, protein carbonyl and DNA modification. Moreover, KIOM-4 treatment restored the loss of mitochondrial membrane potential (Δψ) that was induced by STZ treatment, and inhibited the translocation of cytochrome c from the mitochondria to the cytosol. In addition, KIOM-4 treatment elevated the level of ATP, succinate dehydrogenase activity and insulin level, which were reduced by STZ treatment. These results suggest that KIOM-4 exhibits a protective effect through its antioxidant effect and the attenuation of mitochondrial dysfunction in STZ-induced diabetic cells.
authors.affiliation: School of Medicine, Jeju National University, Jeju-si 690-756, Republic of Korea.
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Maeng
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Kang
authors.forename: In Kyung
authors.initials: IK
authors.lastname: Lee
authors.forename: Bum Joon
authors.initials: BJ
authors.lastname: Kim
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun