Protective effect of apigenin against oxidative stress-induced damage in osteoblastic cells

Romano²,

et al. 2017

Advances in Urology

Peyronie's disease (PD) is a chronic inflammation of tunica albuginea of the corpora cavernosa that causes an inelastic plaque resulting in penis deformation. Although its etiology is not completely known, there is general consensus that PD is genetically transmitted and secondary to penile trauma. In recent years, numerous studies demonstrated the role played by oxidative stress in PD pathogenesis, and other studies have described successful use of antioxidants in PD treatment. Oxidative stress is an integral part of this disease, influencing its progression. In the early stages of PD, the inflammatory infiltrate cells produce high quantities of free radicals and proinflammatory and profibrotic cytokines, with consequent activation of transcription factor NF-κB. While conservative therapies commonly used in the early stages of PD include oral substances (Potaba, tamoxifen, colchicine, and vitamin E), intralesional treatment (verapamil, interferon, steroids, and more recently collagenase clostridium histolyticum-Xiaflex), and local physical treatment (iontophoresis, extracorporeal shock wave therapy, and penile extender), the significant results obtained by emerging treatments with the antioxidants cited in this article suggest these therapeutic agents interfere at several levels with the disease's pathogenetic mechanisms. Antioxidants therapy outcomes are interesting for good clinical practice and also confirm the fundamental role played by oxidative stress in PD.

Section: Pathophysiology Of Peyronie's' Disease (Figure 1)mentioning

confidence: 99%

Recent Pathophysiological Aspects of Peyronie’s Disease: Role of Free Radicals, Rationale, and Therapeutic Implications for Antioxidant Treatment—Literature Review

Romano²,

et al. 2017

Advances in Urology

“…The studies by Hougee et al and Choi showed that apigenin inhibited IL-1b-induced prostaglandin synthesis, tumor necrosis factor (TNF)-induced IL-6 and IL-8 production in human peripheral blood mononuclear cells (PBMC) and TNF-alpha-induced secretion of osteoclastogenic cytokines such as IL-6 in MC3T3-E1 cells [21,22]. In addition, apigenin also attenuated oxidative-induced cell damage and increased osteoblast differentiation genes such as alkaline phosphatase (ALP), collagen, osteopontin (OPN), osteoprotegerin (OPG), bone sialoprotein (BSP), osterix (OSX) and osteocalcin (OC), and bone morphogenetic proteins (BMPs) genes in osteoblastic cells [23]. Furthermore, apigenin inhibited osteoclastogenesis and prevents bone loss in ovariectomized mice [24,25].…”

Section: Introductionmentioning

confidence: 99%

Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways

et al. 2015

Apigenin is a plant-derived flavonoid and has been reported to prevent bone loss in ovariectomized mice, but the role of apigenin on osteogenic differentiation of human mesenchymal stem cells (hMSCs) has not been reported. In the present study, the effect of apigenin on osteogenic differentiation of hMSCs was explored. Our results showed that apigenin treatment significantly increased alkaline phosphatase (ALP) activity and mineralization in hMSCs. RT-PCR revealed that apigenin markedly up-regulated the mRNA expression of osteopontin (OPN) and the transcription factors runt-related transcription factor 2 (Runx2). The expression of Runx2 and osterix (OSX) proteins were also increased in hMSCs differentiating into osteoblasts after treatment with apigenin. Furthermore, we investigated the signaling pathways responsible for osteogenic differentiation of apigenin in hMSCs. We found that apigenin treatment significantly increased the levels of p-JNK, p-p38 in hMSCs and addition of the inhibitors of JNK (SP600125) or p38 MAPK (SB203580) eliminated the stimulating effects of apigenin. In addition, addition of SP600125 or SB203580 also blocked apigenin-induced ALP activity, OPN, Runx2, and OSX expression and meanwhile inhibited bone nodule formation. Taken together, these findings suggest apigenin promotes the osteogenesis of hMSCs through activation of JNK and p38 MAPK signal pathways which leads to Runx2 and OSX expressions to induce the formation of bone nodule.

“…Physiological level of ROS is essential for the maintenance of normal cellular function, while excessive production of ROS leads to mitochondrial damage and cell injury [23, 24]. Given that ROS is noxious products of cellular metabolism and mainly produced by the mitochondria, linking mitochondrial respiration with ROS effects on cellular function is logical.…”

Section: Introductionmentioning

confidence: 99%

Blockade of cyclophilin D rescues dexamethasone-induced oxidative stress in gingival tissue

Zhang

Zhu

et al. 2017

PLoS ONE

Glucocorticoids (GCs) are frequently used for the suppression of inflammation in chronic inflammatory diseases. Excessive GCs usage is greatly associated with several side effects, including gingival ulceration, the downward migration of the epithelium, attachment loss and disruption of transeptal fibers. The mechanisms underlying GCs-induced impairments in gingival tissue remains poorly understood. Mitochondrial dysfunction is associated with various oral diseases, such as chronic periodontitis, age-related alveolar bone loss and hydrogen peroxide-induced cell injury in gingival. Here, we reported an unexplored role of cyclophilin D (CypD), the major component of mitochondrial permeability transition pore (mPTP), in dexamethasone (Dex)-induced oxidative stress accumulation and cell dysfunctions in gingival tissue. We demonstrated that the expression level of CypD significantly increased under Dex treatment. Blockade of CypD by pharmaceutical inhibitor cyclosporine A (CsA) significantly protected against Dex-induced oxidative stress accumulation in gingival tissue. And the protective effects of blocking CypD in Dex-induced gingival fibroblasts dysfunction were evidenced by rescued mitochondrial function and suppressed production of reactive oxygen species (ROS). In addition, blockade of CypD by pharmaceutical inhibitor CsA or gene knockdown also restored Dex-induced cell toxicity in HGF-1 cells, as shown by suppressed mitochondrial ROS production, increased CcO activity and decreased apoptosis. We also suggested a role of oxidative stress-mediated p38 signal transduction in this event, and antioxidant N-acety-l-cysteine (NAC) could obviously blunted Dex-induced oxidative stress. These findings provide new insights into the role of CypD-dependent mitochondrial pathway in the Dex-induced gingival injury, indicating that CypD may be potential therapeutic strategy for preventing Dex-induced oxidative stress and cell injury in gingival tissue.