ABSTRACT
The role of fibrates in treating hypertriglyceridemia in chronic kidney disease (CKD) patients to prevent cardiovascular disease (CVD) has been insufficiently investigated. Since statin is considered the first-line treatment for dyslipidemia in CKD patients, this study aims to evaluate the role of concurrent fibrate therapy with statins among moderate CKD patients. We recruited CKD3 patients from the Chang Gung Research Database who were receiving statin treatment but had not previously been administered ezetimibe or niacin. The participants were divided into two groups based on their use of fibrates (fibrate group) or those with triglyceride levels >200 mg/dL without fibrate treatment (non-fibrate group). The fibrate group (n = 954) only exhibited a significantly lower incidence of AMI (4.4% vs. 5.4%, HR: 0.77, 95% CI: 0.61 to 0.98). The risk of major adverse cardiovascular and cerebrovascular events (14.7% vs. 15.6%, HR: 0.91, 95% CI: 0.72 to 1.15) and all-cause mortality (5.7% vs. 6.1%, HR: 0.91, 95% CI: 0.63 to 1.30) did not significantly differ between the fibrate group and the non-fibrate group (n = 2358). In moderate CKD patients, combining fibrate therapy with statins may not offer additional cardiovascular protection compared to statin alone.
ABSTRACT
The aberrant activation of the purinergic signaling pathway has been shown to promote cyst growth and fluid secretion in autosomal dominant polycystic kidney disease (ADPKD). Suramin is an anti-parasitic drug that has strong anti-purinergic properties. Whether suramin could have a therapeutic effect on ADPKD has not been fully investigated. We examined the effect of suramin on cyst progression in a Pkd1 microRNAs transgenic mouse model that presented stable Pkd1 knockdown and moderate disease progression. The Pkd1-deficient mice were treated with suramin (60 mg/kg) by intraperitoneal injection twice a week from postnatal days 35 to 90. Kidney-to-body weight ratios, cyst indices, and blood urea nitrogen (BUN) levels were measured. Cell proliferation and macrophage infiltration were determined by immunohistochemistry. The suramin-treated group had significantly lower renal cyst densities, cell proliferation, and macrophage infiltration compared with saline-treated controls. Suramin significantly inhibited ERK phosphorylation and the expression of Il1b, Il6, Nlrp3, Tgfb, Fn1, P2rx7, and P2ry2 mRNAs in the kidneys. However, BUN levels remained high despite the reduction in cyst growth. Furthermore, plasma cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) levels were significantly higher in the suramin-treated group compared with the control group. Periodic acid-Schiff staining revealed degenerative changes and epithelial cell vacuolation in the non-cystic renal tubules, which indicated phospholipidosis following suramin treatment. These results suggest that suramin may reduce renal cyst growth and inflammation, but the associated tubular cell injuries could limit its therapeutic potential. Other purinergic receptor antagonists with less nephrotoxicity may deserve further investigation for the treatment of ADPKD.
Subject(s)
Cysts , Polycystic Kidney Diseases , Polycystic Kidney, Autosomal Dominant , TRPP Cation Channels/metabolism , Animals , Cell Proliferation , Cysts/drug therapy , Disease Models, Animal , Kidney/metabolism , Mice , Mice, Transgenic , Polycystic Kidney Diseases/metabolism , Polycystic Kidney, Autosomal Dominant/drug therapy , Polycystic Kidney, Autosomal Dominant/genetics , Polycystic Kidney, Autosomal Dominant/metabolism , Suramin/pharmacology , Suramin/therapeutic use , TRPP Cation Channels/geneticsABSTRACT
White wax (WW) has been traditionally used to treat hair loss in China. However there has been no reporter WW and its extract responsible for hair growth-promoting effect on androgenetic alopecia. In this paper, we examined the hair growth-promoting effects of WW and policosanol of white wax (WWP) on model animal of androgenetic alopecia and the potential target cell of WW and WWP. WW (1, 10 and 20%) and WWP (0.5, 1 and 2%) were applied topically to the backs of mice. Finasteride (2%) was applied topically as a positive control. MTS assays were performed to evaluate cell proliferation in culture human follicle dermal papilla cells (HFDPCs). The inhibition of WW and WWP for 5α- reductase were tested in Vitro. Results showed more lost hairs were clearly seen in mice treated with TP only and TP plus vehicle. Mice which received TP plus WW and WWP showed less hair loss. WW and WWP showed an outstanding hair growth-promoting activity as reflected by the follicular length, follicular density, A/T ratio, and hair bulb diameter. The optimal treatment effect was observed at 10% WW and 1% WWP, which were better than 2% finasteride treatment. MTS assay results suggested that WW and WWP remarkably increased the proliferation of HFDPCs. Inhibitor assay of 5α- reductase showed that WW and WWP inhibited significantly the conversion of testosterone to dihydrotesterone, and the IC50 values of WW and WWP were higher than that of finasteride. In Conclusion, WW and WWP could act against testosterone-induced alopecia in mice, and they promoted hair growth by inhibiting 5α-reductase activity and HFDPCs proliferation. DPCs is the target cell of WW and WWP.
