1.The role of oxidative stress and hypoxia in renal disease
Tomoko HONDA ; Yosuke HIRAKAWA ; Masaomi NANGAKU
Kidney Research and Clinical Practice 2019;38(4):414-426
Oxygen is required to sustain aerobic organisms. Reactive oxygen species (ROS) are constantly released during mitochondrial oxygen consumption for energy production. Any imbalance between ROS production and its scavenger system induces oxidative stress. Oxidative stress, a critical contributor to tissue damage, is well-known to be associated with various diseases. The kidney is susceptible to hypoxia, and renal hypoxia is a common final pathway to end stage kidney disease, regardless of the underlying cause. Renal hypoxia aggravates oxidative stress, and elevated oxidative stress, in turn, exacerbates renal hypoxia. Oxidative stress is also enhanced in chronic kidney disease, especially diabetic kidney disease, through various mechanisms. Thus, the vicious cycle between oxidative stress and renal hypoxia critically contributes to the progression of renal injury. This review examines recent evidence connecting chronic hypoxia and oxidative stress in renal disease and subsequently describes several promising therapeutic approaches against oxidative stress.
Anoxia
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Diabetic Nephropathies
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Kidney
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Kidney Failure, Chronic
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Oxidative Stress
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Oxygen
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Oxygen Consumption
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Reactive Oxygen Species
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Renal Insufficiency, Chronic
2.Neurotropin protects rotator cuff tendon cells from lidocaine-induced cell death
Ryunosuke ABE ; Hiroki OHZONO ; Masafumi GOTOH ; Yosuke NAKAMURA ; Hirokazu HONDA ; Hidehiro NAKAMURA ; Shinichiro KUME ; Takahiro OKAWA ; Naoto SHIBA
Clinics in Shoulder and Elbow 2021;24(4):224-230
Local anesthetics often are used in rotator cuff tears as therapeutic tools, although some cases have reported that they have detrimental effects. Neurotropin (NTP) is used widely in Japan as a treatment for various chronic pain conditions and is shown to have protective effects on cartilage and nerve cells. In this study, we investigated the protective effect of NTP against lidocaine-induced cytotoxicity. Methods: Tenocytes from rotator cuff tendons were incubated with lidocaine, NTP, lidocaine with NTP, and a control medium. Cell viability was evaluated using the WST-8 assay. Cell apoptosis was detected via annexin V staining using flow cytometry. The expression of BCL-2 and cytochrome c, which are involved in the intrinsic mitochondrial pathway of apoptosis, was evaluated via Western blotting and immunohistochemical staining. Results: In the cell viability assay, lidocaine decreased cell viability in a dose-dependent manner, and NTP did not affect cell viability. Moreover, NTP significantly inhibited the cytotoxic effect of lidocaine. The flow cytometry analysis showed that lidocaine significantly induced apoptosis in tenocytes, and NTP considerably inhibited this lidocaine-induced apoptosis. Western blotting experiments showed that lidocaine decreased the protein expression of BCL-2, and that NTP conserved the expression of BCL-2, even when used with lidocaine. Immunohistochemical staining for cytochrome c showed that 0.1% lidocaine increased cytochrome c-positive cells, and NTP suppressed lidocaine-induced cytochrome c expression. Conclusions: NTP suppresses lidocaine-induced apoptosis of tenocytes by inhibiting the mitochondrial apoptotic pathway. Intra-articular/ bursal injection of NTP with lidocaine could protect tenocytes in rotator cuff tendons against lidocaine-induced apoptosis.
3.Relationship between Pain and Muscle Activities of the Knee Joint during Walking in Patients with Severe Knee Osteoarthritis
Yosuke HONDA ; Kei SETOGAWA ; Kiyotaka KAMIYA ; Hiroyuki FUJIOKA ; Shinichi YOSHIYA ; Kazuhisa DOMEN
The Japanese Journal of Rehabilitation Medicine 2018;55(8):702-706
Objective:To investigate the relationship between clinical assessment of pain and muscle activity during walking in patients with severe knee osteoarthritis (OA).Methods:Eleven patients diagnosed as having severe knee OA (13 knees) were evaluated with electromyography and numerical rating scale (NRS) of pain during walking. Electromyography was recorded from the vastus medialis (VM), semitendinosus (ST), vastus lateralis (VL), and biceps femoris (BF) muscles. Co-contraction indexes (CCIs) for the extensor and flexor muscles of the knee joint were calculated as follows:using the VM and ST data for CCI at the medial aspect of the knee and the VL and BF data for CCI at the lateral aspect. Spearman's rank correlation coefficients between the average individual muscle activities or CCI and pain were calculated.Results:During the terminal stance of walking, NRS significantly correlated with the activation patterns of BF (r =-0.61, p<0.05), the CCI of VL-BF (r =-0.582, p<0.05), and the CCI of VM-ST (r =-0.596, p<0.05).Conclusion:This study suggests that pain severity is reflected in increasing CCI at the medial and lateral aspects during the terminal stance phase in severe knee OA.