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 (FeSO4/H2O2), 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.

Therapeutic potential of pterostilbene against pancreatic beta‐cell apoptosis mediated through Nrf2

“…In the present study, the pancreatic beta‐cells were directly exposed to STZ at a dose of 10 mM for 1 h to induce apoptosis. The dosage was chosen based on the LD 50 of the compound, which was supported by previous findings (Kang et al ., ).…”

“…The EC 50 value of PTS in INS‐1E cells was found to be 25 μM, and in further studies doses lower than this were used. To elucidate the protective role of PTS on STZ‐induced cytotoxicity, the cells were pretreated with various doses of PTS in different time points (0–16 μM at 0–48 h), followed by STZ treatment (10 mM) (Kang et al ., ) for 1 h. The time‐dependent study was carried out with doses of PTS up to 8 μM. The % inhibition of cytotoxicity was calculated as a fraction of control and expressed as a % relative to the cell viability with respect to control.…”

Elucidation of Molecular Mechanisms of Streptozotocin‐Induced Oxidative Stress, Apoptosis, and Mitochondrial Dysfunction in Rin‐5F Pancreatic β‐Cells

“…However, decreased expression of the antioxidant responsive protein, Nrf2, was observed after STZ treatment, which decreased drastically after 48 h. Pancreatic cells contain very low levels of antioxidant enzymes; thus, these cells are particularly sensitive to oxidative stress [ 47 ]. Nrf2 is considered a master regulator of the antioxidant response, and decreased expression of Nrf2 by STZ has been shown by various researchers [ 48 , 49 ]. The reason for this loss of Nrf2 expression in pancreatic cells could be due to the STZ-induced increased intracellular ROS and oxidized-to-reduced GSH ratio which has been reported in this study as well as by other researchers.…”

Mulberry Fruit Extract Protects Pancreatic β-Cells against Hydrogen Peroxide-Induced Apoptosis via Antioxidative Activity

“…MIN6N β-cells were labeled using the cell-permeable, DNA specific fluorescent dye Hoechst 33342 [33]. Cells with homogeneously stained nuclei were considered viable, whereas presence of chromatin condensation and/or fragmentation was indicative of apoptosis [34].…”