Therapeutic Effect of a Newly Developed Antioxidative Agent (OPC-15161) on Experimental Immune Complex Nephritis

Sanaka, Tsutomu; Nakano, Yoshimasa; Nishimura, Hideki; Shinobe, Michitaka; Higuchi, Chieko; Omata, Momoyo; Nihei, Hiroshi; Sugino, Nobuhiro

doi:10.1159/000190198

Cited by 15 publications

(10 citation statements)

References 8 publications

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“…Minimal-change disease, membranous glomerulonephritis, neutrophil-induced damage, ischemic or toxic acute renal failure, obstructive nephropathy, and progressive renal failure are kidney diseases where ROS play a role in pathogenesis (10,12). In addition, cobra venom factor (25), daunomycin-induced nephropathy (20), immune complex nephritis (29), Masugi nephritis (38), and adriamycin nephropathy (19) are some examples for oxidative stress inducedproteinuria found in experimental kidney disease models. Antioxidant interventions could be effective in reducing proteinuria with superoxide dismutase (19), dimethyl thiourea (20), catalase (35), probucol (17), and vitamins C and E (15) being utilized in such processes.…”

Section: Discussionmentioning

confidence: 99%

Potential sources of oxidative stress that induce postexercise proteinuria in rats

Kocer¹,

Şentürk²,

Kuru³

et al. 2008

Journal of Applied Physiology

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Exercise-induced proteinuria is a common consequence of physical activity and is caused predominantly by alterations in renal hemodynamics. Although it has been shown that exercise-induced oxidative stress can also contribute to the occurrence of postexercise proteinuria, the sources of reactive oxygen species that promote it are unknown. We investigated the enzymes nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase (XO) as possible sources of oxidative stress in postexercise proteinuria. First, we evaluated the effect of blocking the NADPH oxidase enzyme on postexercise proteinuria. We found a significant increase in urinary protein level, kidney thiobarbituric acid-reactive substances (TBARS), and protein carbonyl content after exhaustive exercise, and NADPH oxidase activity was induced by exercise. Rats that were treated with an NADPH oxidase inhibitor for 4 days before exhaustive exercise showed no increase in kidney TBARS or protein carbonyl derivative level and no proteinuria or NADPH oxidase activation. In the next set of experiments, we investigated the effect of XO blockage on postexercise proteinuria. Oxypurinol, an XO inhibitor was administered to rats for 3 days before exercise. Although XO inhibition significantly decreased kidney TBARS levels and protein carbonyl content in exercised rats, the inhibition did not prevent exercise-induced proteinuria. However, plasma and kidney XO activity was not induced by exercise, but rather it was suppressed under oxypurinol treatment. These results suggest that increased NADPH oxidase activity induced by exhaustive exercise is an important source of elevated oxidative, stress during exercise, which contributes to the occurrence of postexercise proteinuria.

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Section: Discussionmentioning

confidence: 99%

Potential sources of oxidative stress that induce postexercise proteinuria in rats

Kocer¹,

Şentürk²,

Kuru³

et al. 2008

Journal of Applied Physiology

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“…Puromycin aminonucleoside-induced nephritis [31], immune complex nephritis [32], Masugi nephritis [33], adriamycin nephropathy [34] and anti-glomerular basement membrane antibody glomerulonephritis [35] are some examples for oxidant stress-induced proteinuria occurred in experimental kidney disease models. H 2 O 2 administration into the renal artery [36] and antioxidant vitamin deficiency [37] are other two situations in which proteinuria exist.…”

Section: Discussionmentioning

confidence: 99%

Biphasic Pattern of Exercise-Induced Proteinuria in Sedentary and Trained Men

Şentürk¹,

Kuru²,

Koçer³

et al. 2006

Nephron Physiol

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Background/Aims: Exercise-induced proteinuria is a common consequence of physical activity, although its mechanism is not clear. Oxidant stress has been proposed as one of different factors involved in postexercise proteinuria in rats. In this study we investigated whether reactive oxygen radicals generated during exercise play a role in exercise-induced proteinuria in sedentary and trained men. Methods: The validity of oxidant stress following stepwise maximal exercise on proteinuria was investigated in sedentary and trained subjects before and after antioxidant vitamin treatment (A, C, and E) for 2 months. While protein carbonyl content in serum and thiobarbituric acid reactive substances (TBARS) in erythrocytes and urine were used as oxidant stress markers, total protein, albumin, β₂-microglobulin in urine were assayed for proteinuria in five consecutive specimens after exercise. Urines were collected before exercise, then 30 min, 2, 8 and 24 h postexercise. Results: Increased urinary protein levels and mixed type proteinuria were determined after 30 min of exercise in sedentary and trained subjects. Proteinuria was normalized at 2 and 8 h specimens. However, glomerular type proteinuria was identified at 24 h specimen in both groups. Oxidant stress markers were significantly elevated in sedentary and trained subjects. Antioxidant treatment prevented the increase in oxidant stress markers, urinary protein levels and the occurrence of glomerular type proteinuria after exhaustive exercise at 24 h in both groups. Conclusions: These findings suggest that the exercise-induced oxidant stress may contribute to exercise-induced proteinuria in sedentary and trained men.

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“…In addition, the plasma pentosidine level in patients with mild renal dysfunction (creatinine clearance 71–90 ml/min) was 1.8-fold higher than that in normal subjects (p < 0.01), while creatinine and urea-nitrogen levels were not significantly elevated in this group of patients. Although Daimon et al [17]and Sanaka et al [18]reported that the plasma pentosidine level rose with a decrease in the kidney function, such a conclusion was obtained by comparing plasma pentosidine levels of patients undergoing HD or peritoneal dialysis with those of healthy people. In contrast to their study, we compared the pentosidine levels according to the creatinine clearance in patients with CRF in the conservative stage.…”

Section: Discussionmentioning

confidence: 99%

“…Because the oxidation reaction is a requirement of pentosidine production, pentosidine has been recently regarded as a glycoxidation product, and it is attracting attention as a possible marker that reflects oxidation and glycosylation of protein in vivo [17, 18, 19, 20, 21, 22, 23]. In CRF patients, the activity of peroxidase associated with the scavenging system (human plasma glutathione peroxidase) of oxygen radicals and the concentration of selenium, the composing element, is markedly lower as compared with healthy subjects [24].…”

Section: Discussionmentioning

confidence: 99%

“…In CRF patients, the activity of peroxidase associated with the scavenging system (human plasma glutathione peroxidase) of oxygen radicals and the concentration of selenium, the composing element, is markedly lower as compared with healthy subjects [24]. In dialysis patients, the concentration of malonaldehyde, a lipid peroxide, is twofold higher than in healthy subjects [17], and the ratio of oxidized ascorbic acid to ascorbic acid in blood is 2.5-fold higher than in normal subjects [18]. Oxidative stress accompanying renal failure may enhance the pentosidine production.…”

Section: Discussionmentioning

confidence: 99%

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Plasma Pentosidine Levels Measured by a Newly Developed Method Using ELISA in Patients with Chronic Renal Failure

Sanaka¹,

Funaki²,

Tanaka³

et al. 2002

Nephron

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The plasma pentosidine levels in patients with renal disease were measured by a simple method which was established for plasma and urinary pentosidine determinations. The method, which can be completed within a few hours, involves pretreating plasma with proteolytic enzyme (pronase) and measuring the concentration of pentosidine in the sample by ELISA using antipentosidine antibodies. The prepared antibodies showed no cross-reaction with the raw materials for pentosidine synthesis or with compounds having similar structures. SDS-PAGE indicated that the antibodies had a high purity. The reaction of the antibodies and keyhole limpet hemocyanin-pentosidine in the competitive ELISA system was inhibited by free pentosidine. Excellent standard curves for pentosidine determination were obtained. In actual measurements of clinical samples from patients, a good correlation (r = 0.9356) was obtained between the values measured by ELISA and HPLC. The plasma pentosidine level in patients with renal disease correlated significantly with plasma creatinine, urea nitrogen, β₂-microglobulin, and creatinine clearance, indicating its usefulness in evaluating the severity of renal disease. A significant elevation in plasma pentosidine levels was observed in mild renal dysfunction, whereas no significant increases in creatinine and urea nitrogen levels were detected, suggesting that the plasma pentosidine level is useful in the early diagnosis of beginning renal failure. In patients with chronic renal failure, no difference in plasma pentosidine levels was observed between diabetic nephropathy and chronic glomerulonephritis, while a significant correlation was observed with phosphatidylcholine hydroperoxide, suggesting the possibility that the plasma pentosidine level reflects injury due to oxidation. From these results, the quantitative measurement method developed by us is judged to be a superior innovation for measuring pentosidine in body fluids. The plasma pentosidine level may be useful for the early diagnosis of mild renal failure and to estimate the degree of the severity of renal diseases.

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Therapeutic Effect of a Newly Developed Antioxidative Agent (OPC-15161) on Experimental Immune Complex Nephritis

Cited by 15 publications

References 8 publications

Potential sources of oxidative stress that induce postexercise proteinuria in rats

Potential sources of oxidative stress that induce postexercise proteinuria in rats

Biphasic Pattern of Exercise-Induced Proteinuria in Sedentary and Trained Men

Plasma Pentosidine Levels Measured by a Newly Developed Method Using ELISA in Patients with Chronic Renal Failure

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