Tubular function is altered in chronic renal failure (CRF). Whether drug secretion by renal tubules is modified in CRF is questioned because of frequent accumulation of various toxins in CRF. This function mainly involves ATP-dependent drug transporters, particularly P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) 2, both present in apical membrane of epithelial cells. The present study was aimed at determining the changes in P-gp and MRP2 expression induced by experimental CRF in kidney and liver. The relationship between MRP2 and glutathione metabolism changes was examined because MRP2 transports GSSG and glutathione conjugates. Rats underwent either 80% subtotal nephrectomy (Nx) or sham operation, and determinations were performed 3 and 6 wk later. CRF induced a 70--200% rise in protein and mRNA expression of MRP2 after 3 and 6 wk post-Nx in remnant kidney and after 6 wk in liver. However, P-gp expression was unchanged by CRF. Relative to whole kidney mass, total MRP2 levels decreased by only 27% in Nx rats whereas total P-gp levels were reduced by 60%. Renal GSSG and total glutathione levels were increased by 30% in Nx rats, but glutathione-S-transferase (GST) activity was normal; liver GSSG levels and GST activity were reduced in Nx rats. In conclusion, CRF resulted in specific overexpression of MRP2 in kidney and liver. This could be an adaptative response to some elevated circulating toxins. The later MRP2 induction and different glutathione changes in liver compared with kidney suggest different mechanisms for MRP2 induction and/or action in these two tissues.
Sanghuangporus vaninii, called “Sanghuang,” is orally used for health care, tumor, and inflammation treatment in Asia. However, the safety of S. vaninii has not been evaluated. The major compounds analysis showed that aqueous extracts of S. vaninii fruiting body were rich in polysaccharides, nucleotides, and polyphenols. Then, the aqueous was given orally to Sprague–Dawley rats for toxical test. In acute toxicity study, the maximum tolerated dose was 21 g/kg. In 17‐week repeated dose toxicity experiment, all rats had no abnormal reaction among control group, low dose group (0.15 g/kg) and middle dose group (1.00 g/kg). At high dose group (6.00 g/kg), the feces began to darken on 16th day (D16), and turned to drug stained stool on D21, all rats recovered on the 3rd day (D92) of recovery period. During the whole experiment, there were no animal death and no treatment‐related changes in any of the parameters under the all doses. These results indicated the No‐Observed Adverse Effect Level of aqueous extract of S. vaninii fruiting body was 1.0 g/kg.
Background: This study aimed to analyze the distribution of IgG subclasses in diabetic nephropathy (DN) and its association with clinico-pathological features. Methods: Forty DN cases were analyzed to identify IgG subclasses, as well as collagen IV α5, CD34, and KIM-1.Results: Both IgG and its subclasses showed a linear expression and overlapped with collagen IV α5 on glomerular basement membrane (GBM) and some of tubular basement membrane (TBM), without complement deposition. Eleven cases of IgG subclass deposition along both GBM and TBM were associated with more proteinuria. Five cases of TBM-only IgG subclass deposition were accompanied with less KIM-1 positivity and more arteriosclerosis. The major IgG subclasses expressed on GBM were IgG1 and IgG2, while TBM expression was mainly IgG1 and IgG3. Glomerular IgG1-positive status was associated with less CD34 expression, while IgG2-positive status was associated with thicker GBM. Expression of multiple IgG subclasses along TBM showed less KIM-1 positivity and interstitial inflammation than those with isotype or no IgG subclass expression.Conclusions: IgG subclasses were selectively deposited along GBM and TBM in DN, which was determined by their profiles and severity of glomerular/tubular injury. IgG and its subclass deposition is not causal, but the consequence of renal injury and these positive statuses are associated with different DN injuries.
Renal injury is an important factor in the development of chronic kidney diseases that pathologically manifested as renal fibrosis and podocyte damage. In the disease state, renal fibroblasts lead to high expression levels of α-smooth muscle actin (α-SMA), while podocytes undergo epithelial–mesenchymal transition, leading to proteinuria. Celastrol, a bioactive compound in the medicinal plant Tripterygium wilfordii, was found to delay the progression of early diabetic nephropathy and attenuate renal fibrosis in mice with unilateral ureteral obstruction. However, its effect on the renal system in 5/6 nephrectomized (Nx) rats remains unknown. The aim of this study was to explore the protective effects of celastrol and its underlying mechanisms in 5/6 Nx rats. We found that 24 h proteinuria and levels of blood urea nitrogen, serum creatinine, triglycerides, serum P, renal index and cholesterol significantly increased ( P < 0.05), while that of serum albumin decreased significantly in 5/6 Nx rats. After intervention with celastrol, 24 h proteinuria and levels of blood urea nitrogen, serum creatinine, triglycerides, serum P, renal index, and cholesterol significantly decreased, while that of serum albumin significantly increased. Renal tissue pathological staining and transmission electron microscopy showed that celastrol ameliorated kidney injury and glomerular podocyte foot injury and induced significant anti-inflammatory effects. Quantitative polymerase chain reaction (PCR) and western blotting results revealed that nephrin and NEPH1 expression levels were upregulated, whereas α-SMA and Col4a1 expression levels were downregulated in the celastrol group. Celastrol inhibited the expression of transforming growth factor (TGF)-β1/Smad3 signaling pathway-related molecules such as TGF-β1 and P-Smad3. In summary, celastrol contributes to renal protection by inhibiting the epithelial–mesenchymal transdifferentiation and TGF-β1/Smad3 pathways.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.