Journal
ACTA PHARMACOLOGICA SINICA
Volume 34, Issue 4, Pages 515-521Publisher
ACTA PHARMACOLOGICA SINICA
DOI: 10.1038/aps.2012.177
Keywords
rhein lysinate; SAMP10; aging; kidney; glomerulonephritis; superoxide dismutase; malondialdehyde; glutathione peroxidase; TNF-alpha; IL-6; NF-kappa B; collagen
Funding
- National Natural Science Foundation of China [81001439]
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Aim: To investigate the protective effects of rhein lysinate (RHL), a major bioactive constituent of the rhizome of rhubarb (Rheum palmatum Linn or Rheum tanguticum Maxim), against kidney impairment in senescence-prone inbred strain 10 (SAMP10) mice. Methods: SAMP10 mice were orally administered RHL (25 or 50 mg/kg) daily until 50% of the mice died. Senescence-resistant inbred strain 1 (SAMR1) mice administered no drug were taken as control. The kidneys were harvested after animal death, and examined morphologically and with immunochemical assays. The levels of MAD, SOD and GSH-px in the kidneys were measured with a photometric method. The expression of inflammatory factors and related proteins in the kidneys was analyzed using Western blotting. Results: Treatment of SAMP10 mice with RHL had no effect on the body weight or phenotype. However, RHL significantly prolonged the median survival time of SAMP10 mice by approximately 25%, as compared to untreated SAMP10 mice. Compared SAMR1 mice, SAMP10 mice had a significantly lower level of SOD in the kidneys, but had no significant difference in the MDA or GSH-px levels. Treatment of SAMP10 mice with RHL significantly reduced the MAD level, and increased the SOD and GSH-px levels in the kidneys. Glomerulonephritis was observed in SAMP10 mice but not in SAMR1 mice. RHL decreased the incidence of glomerulonephritis, and significantly decreased the levels of TNF-alpha, IL-6, NF-kappa B, collagen types I and III in the kidneys. Conclusion: Accelerated senescence is associated with glomerulonephritis in SAMP10 mice, and RHL prolongs their median survival time by reducing the severity of glomerulonephritis.
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