Grape seed proanthocyanidins inhibit H₂O₂-induced osteoblastic MC3T3-E1 cell apoptosis via ameliorating H₂O₂-induced mitochondrial dysfunction

Abstract

-Oxidative stress represents a major cause of cellular damage and death in pathological conditions including osteoporosis, in which oxidative stress is associated with increased bone resorption and low bone mass. And grape seed proanthocyanidins are a group of polyphenolic bioflavonoids which are known to possess broad pharmacological activity and therapeutic potential, exerting a protective role against oxidant injury. The aim of our study was to investigate whether proanthocyanidins exert an anti-apoptosis effect in osteoblastic MC3T3-E1 cells, via their antioxidant activity. Firstly, we determined the anti-apoptosis effect of proanthocyanidins in osteoblastic MC3T3-E1 cells, which were subject to H 2 O 2 treatment, then we determined the association of the antioxidant activity exerted by proanthocyanidins with their anti-apoptosis effect. Results demonstrated that proanthocyanidins inhibit H 2 O 2 -promoted apoptosis in MC3T3-E1 cells, via ameliorating the viability of MC3T3-E1 cells post H 2 O 2 treatment and reducing the apoptotic cell numbers. And the proanthocyanidins treatment also ameliorates the H 2 O 2 -induced mitochondrial dysfunction via promoting the mitochondrial membrane potential (MMP) and respiratory chain complex IV, and reducing the mitochondrial free radical production, ROS and mitochondrial superoxide. Moreover, the proanthocyanidins inhibit H 2 O 2 -induced apoptosis signaling which is mediated by p53. This study implied a possible anti-osteoporosis effect of proanthocyanidins via their antioxidant and anti-apoptosis activity.

Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction

“…In the oxidative stress model we used, we clearly found that the mitochondrial membrane potential and respiratory chain complex activity were significantly reduced in conditions where production of mitochondrial ROS was significantly up-regulated. This result is consistent with that from a previous study using MC3T3-E1 osteoblasts, where complex IV activity was reduced [32]. Furthermore, to determine whether mitochondrial fission is required for activation-induced ROS generation in osteoblasts, we examined the effect of Drp1 inhibition using a pharmacological Drp1 inhibitor (mdivi-1).…”

Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction

“…A recent study showed that proanthocyanidins could ameliorate H 2 O 2 -induced mitochondrial dysfunction by promoting mitochondrial respiratory chain complex IV and reducing the levels of mitochondrial superoxide 16 . Moreover, grape seed extract can reduce silica-induced and bleomycin-induced pulmonary fibrosis in rats 17 , and GSPs protect mice from RILI by inhibiting the TGF-β1/Smad3/Snail signaling pathway, scavenging hydroxyl radicals (•OH) and modulating the levels of RILI-associated cytokine (interferon-γ, IL-4 and IL-13) derived from Th1/Th2 cells 18 .…”

The New Synthetic H2S-Releasing SDSS Protects MC3T3-E1 Osteoblasts against H2O2-Induced Apoptosis by Suppressing Oxidative Stress, Inhibiting MAPKs, and Activating the PI3K/Akt Pathway

“…These results partly explained the underlying mechanisms for the SDSS effects on ROS scavenging. Mitochondrial dysfunction is also an important target and source of ROS, and is characterized by an increase in membrane permeability, which caused release of cytochrome c. Mitochondrial dysfunction participates in aging-related disease, including osteoporosis (Zhang et al, 2014; Lane et al, 2015). Our data show that cytosolic cytochrome c accumulation induced by H 2 O 2 was significantly alleviated after pretreatment with SDSS.…”