Tempol Alleviates Chronic Intermittent Hypoxia-Induced Pancreatic Injury Through Repressing Inflammation and Apoptosis

Abstract

Obstructive sleep apnea (OSA) has been demonstrated to be implicated in disorder of insulin secretion and diabetes mellitus. In this study, we aimed to evaluate the protective role of tempol, a powerful antioxidant, in chronic intermittent hypoxia (IH)-induced pancreatic injury. The rat model of OSA was established by IH exposure. The pathological changes, increased blood-glucose level, and raised proinsulin/insulin ratio in pancreatic tissues of rats received IH were effectively relieved by tempol delivery. In addition, the enhanced levels of pro-inflammatory cytokines, TNF-α, IL-1β, IL-6, and inflammatory mediators, PGE2, cyclooxygenase-2 (COX-2), NO, and inducible nitric oxide synthase (iNOS) in pancreatic tissue were suppressed by tempol. Moreover, tempol inhibited IH-induced apoptosis in pancreatic tissue as evidenced by upregulated Bcl-2 level, and downregulated Bax and cleaved caspase-3 levels. Finally, the abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways induced by IH was restrained by tempol administration. In summary, our study demonstrates that tempol relieves IH-induced pancreatic injury by inhibiting inflammatory response and apoptosis, which provides theoretical basis for tempol as an effective treatment for OSA-induced pancreatic injury.

Tempol differently affects cellular redox changes and antioxidant enzymes in various lung-related cells

“…Tempol has been shown to protect cells and tissues from oxidative damage 21 , 23 – 26 . In contrast, it has also been reported that Tempol enhances inflammation and oxidative damage in numerous cell and tissue models 21 , 23 .…”

“…Therefore, Tempol is a potential redox agent that may function as a reductive or oxidative mediator depending on its concentration in the cell 21 . Treatment with Tempol removes a variety of ROS and diminishes oxidation, subsequently protecting cells and tissues from oxidative injuries 21 , 23 – 26 . Our previous reports have shown that Tempol prevents lung cancer cells and juxtaglomerular cells from undergoing cell death in response to cytotoxic insult 27 , 28 .…”

miR‑30a‑5p inhibits hypoxia/reoxygenation‑induced oxidative stress and apoptosis in HK‑2 renal tubular epithelial cells by targeting glutamate dehydrogenase 1 (GLUD1)

“…Bax/Bcl-2 as well as cleaved-caspase-3/caspase-3 are critical markers of apoptosis. The former promotes apoptosis, while the latter inhibits apoptosis and they regulate apoptosis by controlling the permeability of mitochondrial membranes (33). In addition, the Bcl-2 gene can regulate the activity of cleaved-caspase-3, which eventually leads to apoptotic cascade (34,35).…”

Tempol Differently Affects Cellular Redox Status and Antioxidant Enzymes in Various Lung-related Cells

“…Tempol has been shown to protect cells and tissues from oxidative damage [23][24][25][26][27] . In contrast, it has also been reported that Tempol enhances in ammation and oxidative damage in numerous cell and tissue models 21,24 .…”

“…Therefore, Tempol is a potential redox agent that may function as a reductive or oxidative mediator depending on its concentration in the cell 21 . Treatment with Tempol removes a variety of ROS and diminishes oxidation, subsequently protecting cells and tissues from oxidative injuries [23][24][25][26][27] . Our previous reports have shown that Tempol prevents lung cancer cells and juxtaglomerular cells from undergoing cell death in response to cytotoxic insult 28,29 .…”