Tangeretin protects renal tubular epithelial cells against experimental cisplatin toxicity

Objective(s): Cisplatin is an effective antineoplastic agent; its clinical utility, however, is limited by a few salient toxic side effects like nephrotoxicity. This study aimed to determine the potential protective effects of tangeretin, a citrus-derived flavonoid, against renal tubular cell injury in cisplatin-induced renal toxicity of rats.Materials and Methods: Tangeretin was injected intraperitoneally at 2.5 and 5 mg/kg doses for 10 days, and a single dose of cisplatin (8 mg/kg) was injected on the 7th day. Tests of kidney function and tubular injury in renal tissues and urine together with oxidative stress and inflammation markers were examined.Results: Tangeretin ameliorated cisplatin-induced elevations in serum creatinine, BUN, and histopathologic changes. It also attenuated kidney oxidative stress elicited by cisplatin as demonstrated by reduced MDA and increased GSH, CAT, and SOD activities, elevated Nrf2 expression and protein levels of its downstream effectors, HO-1 and NQO-1. Tangeretin further alleviated inflammation evoked by cisplatin as indicated by reduced NF-κB p65 subunit phosphorylation with a simultaneous decrement in its downstream effectors IL-1β and TNF-α expression and protein levels. Moreover, it declined caspase-3 protein levels and TUNEL positive cells in the kidneys, the markers of apoptosis and DNA fragmentation, thus improving renal endurance. Additionally, tangeretin mitigated renal levels of KIM-1 and NGAL, as well as urinary cystatin C and β2-microglobulin concentrations, the markers of renal tubular injury.Conclusion: Collectively, these data signify the binary profit of tangeretin: enhancement of renal protective mechanisms against cisplatin and attenuation of renal tubular cell injuries induced by the agent

Empagliflozin alleviates renal inflammation and oxidative stress in streptozotocin-induced diabetic rats partly by repressing HMGB1-TLR4 receptor axis

Objective(s): Empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, possesses verified anti-inflammatory and anti-oxidative stress effects against diabetic nephropathy. The present investigation aims to examine empagliflozin effects on the renal levels of high mobility group box-1 (HMGB1), a potent inflammatory cytokine, and its respective receptor toll-like receptor-4 (TLR-4) in STZ-induced diabetic rats.Materials and Methods: Empagliflozin at 10 mg/kg per os (p.o.) was administered for 4 weeks, starting 8 weeks after the induction of diabetes. Renal function, kidney inflammation, oxidative stress, and apoptosis markers as well as renal HMGB1, receptor for advanced glycation end products (RAGE), and TLR-4 levels were assessed.Results: In addition to down-regulating NF-κB activity in renal cortices, empagliflozin reduced renal levels of HMGB1, RAGE, and TLR-4. It alleviated renal inflammation as indicated by diminished renal expressions of inflammatory cytokines and chemokines like tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) and also decreased urinary levels of interleukin-6 (IL-6) and alpha-1 acid glycoprotein (AGP). Moreover, empagliflozin ameliorated renal oxidative stress as demonstrated by decreased renal malondialdehyde (MDA) and elevated renal activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX). It also suppressed renal caspase-3, the marker of apoptosis; and furthermore, enhanced renal function noticed by the declined levels of serum urea and creatinine.Conclusion: These findings underline that empagliflozin is able to attenuate diabetes-related elevations in renal HMGB1 levels, an influential inflammatory cytokine released from the necrotic and activated cells, and its correspondent receptors, i.e., RAGE and TLR-4

Soluble Tumor Necrosis Factor Like Weak Inducer of Apoptosis and Vitamin D in Hemodialysis Patients: Relation to Carotid Intima-Media Thickness

Cardiovascular disease, as the leading cause of patient death with chronic kidney disease, could be predicted by carotid atherosclerosis. The aim of the present study was to evaluate a possible relationship between serum soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and Vitamin D levels with mean right/left carotid intima-media thickness (cIMT), in the hemodialysis (HD) patients. In this cross-sectional study, serums were obtained from 50 stable chronic HD patients and 39 healthy controls. The serum levels of sTWEAK, Vitamin D, intact parathyroid hormone (iPTH) in both groups, and cIMT were determined in HD patients by standard methods. Serum levels of sTWEAK were higher [808.8 (521.6–5032.4) pg/ml vs. 664.4 (487.4–2955.8) pg/ml (p = 0.006)] and Vitamin D levels were lower [13.4 (2.5–153) ng/ml vs. 27.8 (18.4–59.0) ng/ml (p = 0.001)] in the hemodialysis patients than in the healthy control. No important correlation was found between sTWEAK Vitamin D levels (r = 0.010/p = 0.946), and mean right(r = −0.194/p = 0.178) and left (r = 0.061/p = 0.673) cIMT in the HD patients. Our study shows that sTWEAK levels are elevated in HD patients. This elevation has no association with the cIMT

Sustained delivery efficiency of curcumin through ZSM-5 nanozeolites/ electrospun nanofibers for counteracting senescence of human adipose-derived stem cells

In the present study, ZSM-5 nanozeolite was incorporated into the Poly-epsilon-Caprolactone/Gelatin nanofibers (PCLGEL NFs) for controlled and sustained release of a natural polyphenol, curcumin (CUR) to enhance the prolonged in vitro expansion of human adipose-derived stem cells (hADSCs) without inducing cellular senescence. XRD, FTIR, BET, TGA, FE-SEM, TEM and water contact angle analysis were used to characterize the fabricated nanozeolites and NFs. A study on the drug discharge pattern from the composite CUR@ZSM-5/PCL-GEL electrospun NFs displayed that by loading CUR into the ZSM-5 nanozeolites, the initial burst release was somewhat eliminated, and a sustained and prolonged drug discharge from NFs was obtained. The data set obtained through FE-SEM, LSCM, MTT and PicoGreen assays, qPCR, and western blotting also revealed better cell adhesion and enhanced metabolic activity and proliferation rate for hADSCs cultured on the CUR@ZSM-5/PCL-GEL NFs compared to other types of NFs after 14 and 28 days of incubation. Besides, Utilizing ZSM-5/NFs for sustained and prolonged delivery of CUR not only remarkably reduced the expression levels of p16INK4A, a crucial modulator of cellular senescence but also led to a significant increase in the transcriptional level and activity of hTERT/telomerase and telomere extension, as well as osteoblastic differentiation markers. These findings demonstrated the potential of ZSM-5/NFs for sustained/controlled release of CUR therapeutic molecules in designing a novel platform toward counteracting cellular senescence and achieving sufficient quantities of fresh hADSCs for regenerative medicine applications