ABSTRACT
Background@#Oxidative stress induced by chronic hyperglycemia is recognized as a significant mechanistic contributor to the development of diabetic kidney disease (DKD).Nonphagocytic nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in many cell types and in the kidney tissue of diabetic animals. We designed this study to explore the therapeutic potential of chloroquine (CQ) and amodiaquine (AQ) for inhibiting mitochondrial Nox4 and diabetic tubular injury. @*Methods@#Human renal proximal tubular epithelial cells (hRPTCs) were cultured in highglucose media (30 mM D-glucose), and diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57BL/6J mice. CQ and AQ were administered to the mice via intraperitoneal injection for 14 weeks. @*Results@#CQ and AQ inhibited mitochondrial Nox4 and increased mitochondrial mass in hRPTCs under high-glucose conditions. Reduced mitochondrial ROS production after treatment with the drugs resulted in decreased endoplasmic reticulum (ER) stress, suppressed inflammatory protein expression and reduced cell apoptosis in hRPTCs under high-glucose conditions. Notably, CQ and AQ treatment diminished Nox4 activation and ER stress in the kidneys of STZ-induced diabetic mice. In addition, we observed attenuated inflammatory protein expression and albuminuria in STZ-induced diabetic mice after CQ and AQ treatment. @*Conclusion@#We substantiated the protective actions of CQ and AQ in diabetic tubulopathy associated with reduced mitochondrial Nox4 activation and ER stress alleviation. Further studies exploring the roles of mitochondrial Nox4 in the pathogenesis of DKD could suggest new therapeutic targets for patients with DKD.
ABSTRACT
OBJECTIVES: Chronic pain is one of the most common experiences of humans and a typical psychophysiological disorder. The aim of this study was to measure the psychophysiological responses in chronic pain patients using a biofeedback system, and to compare them with the results from normal healthy subjects. METHODS: Forty two patients with chronic pain (17 males and 25 females, average age 44.67+/-11.10 years) and 42 normal healthy controls (17 males and 25 females, average age 45.17+/-10.46 years) participated in this study. Electromyography (EMG), skin conductance (SC), and skin temperature (ST) were recorded using biofeedback system during the 3 phases (baseline, stress, and recovery) of stress reactivity test, and average values of them were calculated. Difference of values between two groups in each corresponding phase was analyzed with independent t-test, and change of values across phases of stress reactivity test was analyzed with paired t-test (all two-tailed, p<0.05). RESULTS: Compared to normal controls, chronic pain patients had higher value of EMG (baseline : 8.10+/-5.97 micronV vs 4.72+/-1.52 micronV, t=-3.56, p<0.01 ; stress : 11.25+/-6.89 micronV vs 8.49+/-4.78 micronV, t=-2.13, p<0.05 ; recovery : 7.12+/-3.77 micronV vs 4.78+/-1.59 micronV, t= -3.70, p<0.01) and SC (baseline : 1.06+/-1.0 micronS vs 0.42+/-0.29 micronS, t=-4.0. p<0.01 ; stress : 1.87+/-2.05 micronS vs 1.03+/-0.86 micronS, t=-2.47, p<0.05 ; recovery : 1.74+/-1.77 micronS vs 0.64+/-0.59 micronS, t=-3.8, p<0.01) in all the 3 phases. But, skin temperature comparison did not reveal significant differences in all the 3 phases between two groups. CONCLUSION: Psychophysiological responses of chronic pain patients in stress reactivity test were different from those of normal healthy controls. These results suggest that sympathetic nervous system is more activated in chronic pain patients.