Crescentic type nephritis induced by anti-glomerular basement membrane (GBM) serum in rats.

Ito, Mikio; Yamada, Hisaharu; Okamoto, Kazushi; Suzuki, Yoshio

doi:10.1254/jjp.33.1145

Cited by 44 publications

(19 citation statements)

References 9 publications

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“…Our previous study indicated that immunization with rabbit r-G following i.v. injection of rabbit anti GBM serum to rats caused severe glomerular injury, which led to extensive formation of crescents by enhancing the immune response in the autologous phase via the persistent formation of the host antibody against rabbit r-G (6).…”

Section: Discussionmentioning

confidence: 99%

“…injection of 1.0 ml of rabbit anti rat GBM serum into the tail vein in accordance with the method reported previously (6).…”

Section: Methodsmentioning

confidence: 99%

“…We previously established a model of crescentic-type glomerulone phritis closely resembling rapidly progressive glomerulonephritis in humans, which was characterized by severe glomerular lesions with extensive formation of crescents, by im munizing with rabbit r-globulin following i.v. injection of rabbit anti-GBM serum into rats (6).…”

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confidence: 99%

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Studies on antinephritic effect of TJ-8014, a new Japanese herbal medicine (3): Effects on crescentic-type anti-GBM nephritis in rats.

et al. 1990

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Abstract-We investigated the antinephritic effects of TJ-8014, in comparison to dipyridamole, on crescentic-type anti-GBM nephritis in rats. When adminis tration of test drugs was started from the heterologous phase (from the day after the anti-GBM serum injection), TJ-8014 at 2.0 g/kg/day, p.o., markedly inhibited the urinary protein excretion and elevations of plasma cholesterol and urea nitrogen levels as well as glomerular histopathological changes (i.e., crescent formation, adhesion and fibrinoid necrosis) throughout the 40-day observation period. TJ 8014 at 0.1 and 0.5 g/kg/day, p.o., and dipyridamole at 0.4 g/day, p.o., inhibited only the histopathological changes. When treatment was started from the auto logous phase (from the 22nd day after the anti-GBM serum injection) after the disease had been established, only the high dose of 5.0 g/kg/day of TJ-8014, p.o., was effective in improving the histopathological changes of the established nephritis, as assessed on the 53rd day. The !ow doses of TJ-8014 and dipyridamole were ineffective.These results suggest that TJ-8014 may be a useful Japanese herbal medicine against rapidly progressive glomerulonephritis, which is char acterized by severe glomerular lesions with the extensive formation of crescents. Furthermore, the mechanisms of action of this medicine will be discussed.

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Section: Discussionmentioning

confidence: 99%

“…injection of 1.0 ml of rabbit anti rat GBM serum into the tail vein in accordance with the method reported previously (6).…”

Section: Methodsmentioning

confidence: 99%

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Studies on antinephritic effect of TJ-8014, a new Japanese herbal medicine (3): Effects on crescentic-type anti-GBM nephritis in rats.

et al. 1990

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“…1 Induction of crescentic-type anti-GBM nephritis Crescentic-type anti-GBM nephritis was inducted by immunizing rats that had received a nephritogenic dose of rabbit anti-rat GBM (anti-GBM) serum with rabbit y globulin (rgG) according to a slight modification of the previously reported method (8). Fifty rats weighing approx.…”

Section: Drugsmentioning

confidence: 99%

“…To elucidate the antinephritic actions and mecha nisms of OB-5 in an experimental model of rapidly progressive glomerulonephritis, we investigated the effects of OB-5 on crescentic-type anti-GBM nephritis, which has more severe proteinuria and proliferation of glomerular cells than those of the original-type model (8). In addition, we undertook studies utilizing mono clonal antibody against total leukocytes (OX-1), macro phages (ED-1), cytotoxic/suppressor T cell (OX-8), la positive cells (RT1B) and IL-2 positive cells (OX-39) to detect the effect of OB-5 on the number of these cells in the glomeruli of nephritic rats.…”

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Studies on the Antinephritic Effects of Plant Components (6): Antinephritic Effects and Mechanisms of Phellodendrine (OB-5) on Crescentic-Type Anti-GBM Nephritis in Rats (2).

et al. 1992

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ABSTRACT-Effects of phellodendrine (OB-5) on crescentic-type anti-GBM nephritis in rats and the cell number of the various leukocyte subpopulations in the glomeruli of the nephritic rats were investi gated. OB-5 at 25, 50 and 100 mg/kg/day, p.o. prevented the urinary protein excretion by the 19th day after i.v.-injection of anti-GBM serum. In the OB-5-treated rats, plasma cholesterol and creatinine con tents were lower than those of the control rats throughout the 40-day experimental period. Histopatho logical observations demonstrated that OB-5 inhibited the incidence of crescent formation, adhesion and fibrinoid necrosis in the glomeruli by the 41st day. OB-5 did not affect the plasma antibody titer against rabbit gamma globulin. The increases in total leukocytes, macrophages, cytotoxic/suppressor T cells, la positive cells, and IL-2 receptor positive cells in the glomeruli in OB-5, 100 mg/kg-treated rats as well as those of the animals treated with azathioprine or cyclosporin A were lower than those of the anti-GBM nephritic control. These results indicate that OB-5 was effective in crescentic-type anti-GBM nephritis and the antinephritic mechanisms of this agent may be due to its ability to inhibit the prolifera tion or the migration of macrophages and cytotoxic T lymphocytes in the glomeruli.

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EOS789, pan‐phosphate transporter inhibitor, ameliorates the progression of kidney injury in anti‐GBM‐induced glomerulonephritis rats

Tsuboi¹,

Ichida²,

Murai³

et al. 2022

Pharmacology Res & Perspec

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Hyperphosphatemia associated with chronic kidney disease (CKD) not only dysregulates mineral metabolism and bone diseases, but also strongly contributes to the progression of kidney disease itself. We have identified a novel drug for hyperphosphatemia, EOS789, that interacts with several sodium‐dependent phosphate transporters (NaPi‐IIb, PiT‐1, and PiT‐2) known to contribute to intestinal phosphate absorption. In this study, we investigated whether EOS789 could ameliorate kidney disease progression in glomerulonephritis rats. Anti‐glomerular basement membrane (GBM) nephritis was induced in rats by intravenously administering two types of anti‐rat GBM antibodies. We evaluated the effect of EOS789 administered in food admixture on hyperphosphatemia and kidney disease progression. In an anti‐GBM nephritis rats, which exhibit a significant increase in serum phosphate and a decline in renal function, EOS789 dose‐dependently improved hyperphosphatemia and EOS789 at 0.3% food admixture significantly ameliorated kidney dysfunction as shown in the decline of serum creatinine and BUN. Renal histopathology analysis showed that EOS789 significantly decreased crescent formation in glomeruli. To elucidate the mechanism underlying glomerular disease progression, human mesangial cells were used. High phosphate concentration in media significantly increased the expression of Collagen 1A1, 3A1, and αSMA mRNA in human mesangial cells and EOS789 dose‐dependently suppressed these fibrotic markers. These results indicate that EOS789 prevented glomerular crescent formation caused by mesangial fibrosis by ameliorating hyperphosphatemia. In conclusion, EOS789 would not only be useful against hyperphosphatemia but may also have the potential to relieve mesangial proliferative glomerulonephritis with crescent formation.

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Crescentic type nephritis induced by anti-glomerular basement membrane (GBM) serum in rats.

Cited by 44 publications

References 9 publications

Studies on antinephritic effect of TJ-8014, a new Japanese herbal medicine (3): Effects on crescentic-type anti-GBM nephritis in rats.

Studies on antinephritic effect of TJ-8014, a new Japanese herbal medicine (3): Effects on crescentic-type anti-GBM nephritis in rats.

Studies on the Antinephritic Effects of Plant Components (6): Antinephritic Effects and Mechanisms of Phellodendrine (OB-5) on Crescentic-Type Anti-GBM Nephritis in Rats (2).

EOS789, pan‐phosphate transporter inhibitor, ameliorates the progression of kidney injury in anti‐GBM‐induced glomerulonephritis rats

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