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Rapamycin attenuates the severity of murine adriamycin nephropathy
Sing Leung Lui1, Ryan Tsang, Kwok Wah Chan
1Dr. Lee Iu Cheung Memorial Renal Research Center, Tung Wah Hospital, Hong Kong SAR, China.
Background:
Rapamycin is an immunosuppressive drug with potent antifibrotic activity. We evaluated the effect of rapamycin on murine adriamycin nephropathy, a model of progressive glomerulosclerosis and tubulointerstitial fibrosis.
Methods:
Adriamycin nephropathy was induced in Balb/c mice by a single intravenous injection of adriamycin. The mice were treated orally with either saline or rapamycin, beginning at the time of adriamycin injection or rapamycin starting 1 week after adriamycin injection. The mice were sacrificed 6 weeks after adriamycin injection.
Results:
Saline-treated mice developed massive proteinuria and impaired renal function. Kidney sections from saline-treated mice showed marked focal segmental glomerulosclerosis, tubular dilation with protein cast deposition, interstitial fibrosis, and numerous infiltrating macrophages and T lymphocytes. The intrarenal expression of Collagen I and RANTES was also increased. In contrast, both groups of rapamycin-treated mice had markedly reduced proteinuria and preserved renal function, with only mild histological abnormalities. The intrarenal expression of Collagen I and RANTES was reduced, concomitant with a significant reduction in interstitial inflammatory cell infiltration.
Conclusions:
Rapamycin is effective in attenuating the glomerular and tubulointerstitial abnormalities in adriamycin nephropathy. The beneficial effects of rapamycin are mediated, at least in part, through reduced RANTES expression and inflammatory cell infiltration.
Insights
Rapamycin effectively treats adriamycin-induced kidney disease in mice by reducing fibrosis and inflammation. This immunosuppressive drug preserves renal function and mitigates glomerulosclerosis and tubulointerstitial damage.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Rapamycin, an immunosuppressant, exhibits significant antifibrotic properties.
- Adriamycin-induced nephropathy serves as a model for progressive glomerulosclerosis and tubulointerstitial fibrosis.
Purpose of the Study:
- To investigate the efficacy of rapamycin in a murine model of adriamycin nephropathy.
- To assess rapamycin's impact on renal function, histological damage, and fibrotic markers.
Main Methods:
- Adriamycin nephropathy was induced in Balb/c mice via intravenous injection.
- Mice received either saline or rapamycin treatment concurrently with or after adriamycin administration.
- Renal function, proteinuria, and kidney histology were evaluated six weeks post-injection.
Main Results:
- Saline-treated mice exhibited severe proteinuria, impaired renal function, and significant glomerulosclerosis and tubulointerstitial fibrosis.
- Rapamycin treatment markedly reduced proteinuria and preserved renal function, with only mild histological changes.
- Rapamycin decreased intrarenal Collagen I and RANTES expression and reduced inflammatory cell infiltration.
Conclusions:
- Rapamycin effectively attenuates glomerular and tubulointerstitial abnormalities in adriamycin nephropathy.
- The therapeutic benefits of rapamycin are partly attributed to decreased RANTES expression and inflammatory cell infiltration.
