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Biomedical subjects

A Hishida

Publications and source records attributed to A Hishida.

At least 91 records · Page 5Linked to original sources
PubMed1997

Roles of reactive oxygen species and antioxidant enzymes in murine daunomycin-induced nephropathy.

We evaluated the roles of reactive oxygen species and intrinsic antioxidant enzymes in the development of daunomycin (DM)-induced nephropathy in mice. A single dose of DM (20 mg/kg intravenously) induced proteinuria by day 7 and the nephrotic syndrome by day 14 in DM-sensitive strain (A/J) but not in DM-resistant strain (C57BL/6J) (B6). Renal cortical lipid peroxide levels in the A/J mice significantly increased at days 2, 4, and 7 after DM injection, whereas no increase was observed in the B6 mice. The resistance to DM in B6 mice was associated with higher activities in renal cortical superoxide dismutase and glutathione peroxidase. The administration of superoxide dismutase or of dimethylthiourea significantly suppressed the DM-induced proteinuria in the A/J mice. Four days of superoxide dismutase or dimethylthiourea administration suppressed the proteinuria. These findings suggested that murine DM-nephropathy appeared to be mediated by reactive oxygen species and that intrinsic antioxidant enzyme activities may play an important role in the susceptibility to DM-induced nephropathy in mice.

Albuminuria↗
PubMed1997

Acquired resistance to rechallenge injury with uranyl acetate in LLC-PK1 cells.

This study was conducted to determine whether cultured renal cells exposed to previous uranium injury would be resistant to subsequent insult, and if so, the mechanisms for this resistance. The addition of a toxic dose of uranyl acetate (UA) (1 X 10(-3) mol/L) for 48 hours to the culture medium significantly enhanced the release of lactate dehydrogenase (LDH) from LLC-PK1 cells, expressed as LDH activity in the medium corrected by protein content of the cells, compared with control conditions (31.5 +/- 3.6 vs 5.5 +/- 0.6 Wroblewski unit/microg protein, p < 0.01). Pretreatment with a toxic dose of UA (1 x 10(-3) mol/L for 24 hours) or heat stress (42 degrees C for 30 minutes) significantly lessened the extent of increase in LDH after exposure to toxic doses of UA for 48 hours (15.2 +/- 1.4 and 7.6 +/- 0.6 Wroblewski unit/microg protein, respectively). Pretreatment with a nontoxic dose of UA (3 x 10(-4) mol/L for 24 hours) had no effect on the release of LDH after a toxic dose of UA treatment (38.6 +/- 7.0 Wroblewski unit/microg protein). Quercetin (100 microm ) and staurosporine (0.1 microg/ml), both known to inhibit the development of thermotolerance, hindered acquisition of the resistance to rechallenge with UA (42.5 +/- 1.1 and 38.9 +/- 1.8 Wroblewski unit/microg protein, respectively). Quercetin did not modify the UA-induced increase in the release of LDH in cells not pretreated with UA or heat stress. It follows from these findings that LLC-PK1 cells previously exposed to a toxic dose of UA are resistant to rechallenged insult and that mechanisms similar to those for thermotolerance might contribute to this acquired resistances.

Animals↗
PubMed1997

Ultrastructural background of albuminuria in rats with passive Heymann nephritis.

BACKGROUND: Although it is widely known that proteinuria in rats with passive Heymann nephritis (PHN) is prevented by treatment with cobra venom factor (CVF), the precise mechanisms of complement-dependent proteinuria have not been fully elucidated. The aim of this study was to evaluate morphologically whether the size of subepithelial electron-dense deposits (EDDs) contributes to the onset of albuminuria. METHODS: The size of subepithelial EDDs and anionic sites in the lamina rarae externa (LRE) overlaid with subepithelial EDDs were evaluated by ruthenium red and compared between PHN and PHN treated with CVF in rats. RESULTS: Overt albuminuria was present on days 3 and 4 after injection of anti-Fx1A. CVF-treatment of rats with PHN prevented albuminuria (PHN + CVF: n = 6) (53.6 +/- 38.8 vs 1.02 +/- 0.55 mg/day, P < 0.01, on day 4). Rat C3 was detected along the glomerular capillary walls on day 4 post-injection in rats with PHN, but not in rats with PHN + CVF. Subepithelial EDDs were observed in both groups. Quantitative morphometric analysis revealed that CVF-treatment decreased the size of subepithelial EDDs as well as the extent of retraction of glomerular epithelial cells. In both groups the density of anionic sites in the LRE overlaid with EDDs was decreased compared with the LRE without subepithelial EDDs. However, no difference was noted between the two groups. CONCLUSIONS: Depletion of serum complement decreases subepithelial EDDs as well as the number of sites with decreased anionic charge underlying the EDDs. Thus, the size of subepithelial EDDs plays a pivotal role in the onset of albuminuria.

Albuminuria↗
PubMed1997

Uninephrectomy prevents the ischemia-induced increase in renin activity.

Contralateral uninephrectomy attenuates unilateral ischemic injury. The present work was performed to elucidate whether the beneficial effect of uninephrectomy was associated with the modification of ischemia-induced changes in plasma or renal renin activity. A 60-min left renal artery occlusion was conducted in right nephrectomized (Nx) and sham-nephrectomized (Sham-Nx) rats. The decline in inulin clearance 48 h after ischemia was significantly less in Nx rats than in Sham-Nx animals (0.50 +/- 0.10 vs. 0.052 +/- 0.029 ml/min/kidney, p < 0.05). Following ischemia, plasma renin activity (PRA) significantly increased in Sham-Nx (from 5.4 +/- 0.9 to 15.5 +/- 1.4 ng AI/ml/min, p < 0.01) but not in Nx (from 3.5 +/- 0.5 to 5.0 +/- 1.0 ng AI/ml/ min) animals. PRA and renal cortical renin content (2,200 +/- 225 vs. 1,257 +/- 187 ng AI/h/mg protein, p < 0.05) were significantly less in Nx rats than in Sham-Nx animals 48 h after renal ischemia. The decrease in body weight was greater in Nx rats than in Sham-Nx animals. Plasma atrial natriuretic peptide (ANP) (195 +/- 30 vs. 302 +/- 40 pg/ml, p < 0.05) and renal dopamine (DA) content (3.2 +/- 0.5 vs. 13.7 +/- 1.3 ng/g tissue, p < 0.01) were rather lower in the Nx group when compared with the Sham-Nx group. No significant difference was found in the intrarenal content of norepinephrine (NE) between two ischemic groups. These findings suggested that uninephrectomy prevents the ischemia-induced increase in renin activity. The prevention of the increase in renin activity in Nx rats is not be mediated through the modulation of ischemia-induced changes in sodium balance, plasma ANP level and/or intrarenal contents of NE and DA.

Animals↗
PubMed1997

[Acquired resistance to acute renal failure in cisplatin-induced renal failure of rats].

Studies were performed to investigate whether prior cisplatin-induced acute renal failure affords resistance to a second challenge with cisplatin in Sprague-Dawley rats. Both the increase in serum creatinine and tubular damage following a challenge with cisplatin (5 mg/kg, i. p.) were significantly less in rats which had received cisplatin (3 mg/kg, i. p.) 14 days prior to the rechallenge compared with the previously untreated animals. Attenuation of nephrotoxicity was more obvious in the histological index than in the increase in serum creatinine, and increase in serum creatinine concentration did not correlate with tubular necrosis. There were fewer tubular cells that expressed proliferating cell nuclear antigen in previously treated kidneys, suggesting that the enhanced regeneration of tubular cells plays a minor role in the decrease of tubular damage in kidneys recovering from prior acute renal failure. These findings suggest that rats recovering from previous acute renal failure are resistant to a second insult with cisplatin and that the attenuation of nephrotoxicity is more prominent in histological damage than in functional disturbance.

Acute Kidney Injury↗
PubMed1996

Expression of transforming growth factor-beta isoforms in human glomerular diseases.

Protein and mRNA expression of TGF-beta isoforms, TGF-beta 1, -beta 2 and -beta 3, and deposition of fibronectin containing extra domain A (fibronectin EDA+) and plasminogen activator inhibitor-1 (PAI-1) were studied in human chronic glomerulonephritis and diabetic nephropathy. Normal kidneys showed similar, weak immunostaining for all three TGF-beta isoforms. TGF-beta mRNA expression was weak for all isoforms with TGF-beta 1 > TGF-beta 3 >> TGF-beta 2. In thin basement membrane disease and minimal change disease, disorders where extracellular matrix accumulation is not a feature, immunoreactivity and mRNA expression did not differ from normal. In contrast, diseases characterized by extracellular matrix accumulation (IgA nephropathy, focal and segmental glomerulosclerosis, crescentic glomerulonephritis, lupus nephritis and diabetic nephropathy) all showed significantly increased expression of the three TGF-beta isoforms in glomeruli and the tubulointerstitium. While glomerular and tubulointerstitial deposition of two matrix components induced by TGF-beta, fibronectin EDA+ and PAI-1, was significantly elevated in all diseases with matrix accumulation, correlation analysis revealed a close relationship primarily with TGF-beta 1. We conclude that, for a spectrum of human glomerular disorders, increased protein expression of all three TGF-beta isoforms and proteins induced by TGF-beta is associated with pathological accumulation of extracellular matrix.

Antibody Specificity↗
PubMed1996

Uninephrectomy reduces apoptotic cell death and enhances renal tubular cell regeneration in ischemic ARF in rats.

Contralateral uninephrectomy attenuates unilateral ischemic renal injury functionally and morphologically. In this study we investigated the effects of uninephrectomy on apoptotic renal cell death and tubular regeneration in ischemic acute renal failure (ARF) in rats. Unilateral ischemic injury was provoked by a 60-min left renal artery occlusion in right-nephrectomized (Nx) and sham-nephrectomized (sham-Nx) rats. Uninephrectomy attenuated tubular damage 48 h following the renal ischemia Apoptotic cells were found in renal tissue as early as 3 h after reperfusion and increased in number by 12 h. The "ladder" pattern of DNA fragments on agarose gel electrophoresis was also apparent in ischemic kidney. Uninephrectomy reduced apoptotic cells and DNA fragmentation. The expression of proliferating cell nuclear antigen (PCNA) could be seen 24 h after reperfusion and progressively increased thereafter PCNA expression in ischemic kidney was greater in Nx than sham-Nx rats at 24 h after renal reperfusion. These data suggest that uninephrectomy reduces apoptotic cells and DNA fragmentation and enhances PCNA expression. The reduced apoptotic cell death and enhanced cell regeneration may be importantly involved in the uninephrectomy-induced attenuation of ischemic acute renal failure in rats.

Acute Kidney Injury↗
PubMed1996

1,5-anhydroglucitol as a marker for the differential diagnosis of acute and chronic renal failure.

Serum creatinine and 1,5-anhydroglucitol (1,5-AG) were measured in 21 non-dialysis acute renal failure (ARF) and 32 chronic renal failure (CRF) patients. Fasting blood glucose was under 100 mg/dl and no patient had a history of diabetes mellitus. Serum 1,5-AG decreased with increase in serum creatinine in CRF, but not in ARF patients. A significant negative correlation was found between serum 1,5-AG and creatinine in CRF patients (r = -0.592, p < 0.001). Serum 1,5-AG in patients with serum creatinine of 4 mg/dl or more was less than the lowest limit of the normal range in 14 of 15 CRF patients, but only 2 of 12 ARF patients. In these 27 patients, serum 1,5-AG was significantly higher in ARF than CRF (19.0 +/- 5.9 vs. 7.2 +/- 4.1 micrograms/ml, p < 0.01). From these results, it would follow that serum 1,5-AG should serve effectively as a marker for the differential diagnosis of nondiabetic ARF and CRF.

Acute Kidney Injury↗