FOOD SCIENCE AND TECHNOLOGY RESEARCH
·
2023
·
IF 0.6
Yunfan Liu,Jiazhou Zhai,Fei Qin,Liping Gao,Yongxin She,Mengqiang Wang
The aim of this study was to investigate the protective effect of polyphenol extract from Highland barley (HBPE) on cisplatin (CDDP)-induced oxidative damage and mitochondrial damage in rat kidney. The experimental rats were divided into control group, CDDP group, HBPE (600 mg/kg) group, CDDP+HBPE (150 mg/kg) group, CDDP+HBPE (300 mg/kg) group and CDDP+HBPE (600 mg/kg) group. Rats in each group were intragastrically fed with normal saline and corresponding dose of HBPE for 21 d. On the 16th day, CDDP group and CDDP+HBPE group were injected intraperitoneally with CDDP (7.5 mg/kg), and the other groups were injected with the same amount of normal saline. On the 22nd day, the rats were killed and blood samples were taken to detect the contents of blood urea nitrogen (BUN) and creatinine (CrE) in serum, and calculate the kidney index. The kidney samples were used for the measurement of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), hexokinase (HK), and processed for histopathological examinations. The results showed that HBPE improved the abnormalities of serum CrE, BUN, antioxidant and carbohydrate metabolic enzymes in kidney induced by CDDP. HBPE can also reduce the degeneration of renal tubules and glomerular atrophy. Therefore, HBPE has a significant protective effect on oxidative stress injury and mitochondrial damage induced by CDDP in rats.
研究领域:
药理学
·
毒理学
·
肾病学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
PHARMACEUTICAL BIOLOGY
·
2023
·
IF 3.8
Shouhai Wu,Meixia Yan,Junyi Liu,Yizhen Li,Ruimin Tian,Chuang Li,Lihuang Huang,Zhisheng Lu,Peng Xu,Wei Mao
Context Clerodendranthus spicatus Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN).Objective To investigate the molecular mechanism of action of CS in HN treatment using in vivo and in vitro experiments.Materials and methods Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For in vitro studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN.Results HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA (p < 0.05) and blood urea nitrogen (p < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC50 value of UA (uric acid) in HK2 cells was 826.32 ± 3.55 μg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. In vivo and in vitro studies showed that CS inhibited NF-κB phosphorylation and inhibited α-smooth muscle actin (α-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function.Discussion and conclusions These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.
研究领域:
药理学
·
分子生物学
·
肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Ling Guo,Hanyu Yan,Qinqin Gong,Weili Zheng,Liang Zhong,Tao Gong,Xun Sun,Zhirong Zhang,Yuan Ping,Zilan Zhu,Jian Xu,Yongping Zhang
Membranous nephropathy (MN) is a common immune-mediated glomerular disease that requires the development of safe and highly effective therapies. Celastrol (CLT) has shown promise as a therapeutic molecule candidate, but its clinical use is currently limited due to off-target toxicity. Given that excess levels of reactive oxygen species (ROS) contributing to podocyte damage is a key driver of MN progression to end-stage renal disease, we rationally designed ROS-responsive cationic polymeric nanoparticles (PPS-CPNs) with a well-defined particle size and surface charge by employing poly(propylene sulfide)–polyethylene glycol (PPS–PEG) and poly(propylene sulfide)–polyethylenimine (PPS–PEI) to selectively deliver CLT to the damaged glomerulus for MN therapy. Experimental results show that PPS-CPNs successfully crossed the fenestrated endothelium, accumulated in the glomerular basement membrane (GBM), and were internalized by podocytes where rapid drug release was triggered by the overproduction of ROS, thereby outperforming nonresponsive CLT nanotherapy to alleviate subepithelial immune deposits, podocyte foot process effacement, and GBM expansion in a rat MN model. Moreover, the ROS-responsive CLT nanotherapy was associated with significantly lower toxicity to major organs than free CLT. These results suggest that encapsulating CLT into PPS-CPNs can improve efficacy and reduce toxicity as a promising treatment option for MN.
研究领域:
肾病学
·
药学
·
纳米技术
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF TOXICOLOGY
·
2018
·Vol. 92
·期 4
·1421-1434
·
IF 5.728
Jiang Shengwei,Lin Yuchun,Yao Huan,Yang Chuanli,Zhang Liyin,Luo Bing,Lei Zhao,Cao Liwei,Lin Naibo,Liu Xiangyang,Lin Zhongning,He Chengyong
Unfolded protein response (UPR) and endoplasmic reticulum (ER)-phagy are essential for cell homeostasis. Quantum dots (QDs), which have been widely used for biomedical applications, can accumulate in the kidney tissues and may cause renal dysfunction. However, the molecular mechanism of QDs-induced nephrotoxicity is still obscure. The present study was aimed to elucidate the role and mechanism of UPR and ER-phagy in QDs-induced nephrotoxicity. Herein, human embyronic kidney (HEK) cells were exposed to 15, 30, 45, and 60 nM cadmium telluride (CdTe)-QDs for 12 and 24 h. And CdTe-QDs (30–60 nM) inhibited the HEK cell viability. The clathrin-dependent endocytosis was determined as the main pathway of CdTe-QDs cellular uptake. Within cells, CdTe-QDs disrupted ER ultrastructure and induced UPR and FAM134B-dependent ER-phagy. Blocking UPR with inhibitors or siRNA rescued the FAM134B-dependent ER-phagy, which was triggered by CdTe-QDs. Moreover, suppression of UPR or FAM134B-dependent ER-phagy restored the cell vability. In vivo, mice were intravenously injected with 8 and 16 nmol/kg body weight CdTe-QDs for 24 h. Kidney was shown as one of highest distributed organs of CdTe-QDs, resulting in renal dysfunction, as well as UPR and FAM134B-dependent ER-phagy in it. Thus, for the first time, we demonstrated that ER-phagy can be triggered by nanomaterials both in vitro and in vivo. In addition, blocking of UPR and ER-phagy showed protective effects against CdTe-QDs-induced toxicity in kideny cells. Notably, a secreted alkaline phosphatase reporter gene system has been developed as a sensitive and rapid method for evaluating the ER quality under the exposure of nanomaterials.
研究领域:
毒理学
·
细胞生物学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Contemporary Clinical Trials
·
2022
·
IF 2.261
Xiaocong Zhang,Chun Yao,Qunlin Xiao,Jiansheng Wu,Guifu Wu
Background Contrast-induced acute kidney injury (CI-AKI) is a common complication after exposure to contrast media. Renal ischaemia occurs in the initial stage of CI-AKI, however, there are very few effective measures to improve renal perfusion . Methods A total of 114 patients with an estimated glomerular filtration rate (eGFR) of 60–89 ml/min/1.73m 2 were randomly assigned to two groups: enhanced external counterpulsation (EECP) group ( N = 57) and control group (N = 57). Two hours after contrast exposure, EECP group received EECP treatment for 1 h while no intervention was performed control group. The primary outcome was the incidence of serum cystatin C concentration to 10% above the baseline concentration at 24 h after contrast administration. The secondary outcomes were the incidence of CI-AKI (defined as an increase in serum creatinine concentration to ≥0.5 mg/dl or by 25% compare to the baseline after contrast exposure), contrast clearance and adverse clinical events. Results The primary outcome was observed in 26 patients (6 EECP and 20 control; 11% vs. 35%; P = 0.002). CI-AKI occurred in four patients (0 EECP and 4 control; 0% vs. 7%; P = 0.042). The clearance rate of iopromide in the initial 3 h was significantly different between EECP and control group (59.92 ± 8.84 vs 46.80 ± 9.26 ml/min/1.73 m 2 ; P < 0.001). No adverse clinical events were observed in this study. Conclusions This study demonstrates that EECP increases the contrast clearance and may have an effect in reducing the risk of CI-AKI. The study has been registered in Chinese Clinical Trial Registry (ChiCTR 2,000,039,190).
研究领域:
肾病学
·
心脏病学
·
临床研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Huijuan Zhang,Qingqing He,Jingjing Wang,Yaping Wang,Xiangyang Xuan,Mingli Sui,Zhenzhong Zhang,Lin Hou
Glomerulonephritis is a key factor in leading to end-stage renal disease. Mesangial cell proliferation and macrophage infiltration are two prominent features linked in a vicious circle mechanism for glomerulonephritis progression. Herein, a novel biomimetic pH-sensitive nanomicelle (MM/HA-DXM) was constructed to synergize hyaluronic acid (HA)-activated macrophage phenotypic remodeling and dexamethasone (DXM)-mediated mesangial cell killing for precise treatment of glomerulonephritis. Owing to the camouflaged coating with endogenous macrophage membrane (MM), MM/HA-DXM could escape from RES phagocytosis and then be recruited to inflammatory glomerulus by active homing effect. Afterwards, HA-DXM nanomicelles ruptured in response to the weakly acidic glomerulonephritis microenvironment, to locally release HA and DXM . On the one hand, DXM can inhibit the abnormal proliferation of mesangial cells. On the other hand, HA transformed pro-inflammatory M1 macrophages into anti-inflammatory M2 phenotype to improve the glomerular inflammatory microenvironment. In doxorubicin-induced glomerulonephritis models, results revealed that MM/HA-DXM could specifically “homing” to inflammatory renal tissue with 4.33-fold improvement in targeting performance. In addition, in vivo pharmacodynamic results proved that after treatment with MM/HA-DXM, the proteinuria level decreased to 2.33 times, as compared with that of control group, demonstrating a superior therapeutic effect on glomerulonephritis via this collaborative two-pronged anti-inflammatory therapy strategy.
研究领域:
纳米技术
·
药学
·
免疫学
·
肾脏生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Communication and Signaling
·
2025
·Vol. 23
·期 1
·1-17
·
IF 8.9
Wang Jing,Li Zuo-Lin,Zhou Yan,Li Zhong-Tang,Tu Yan,Hu Xin-Hui,Zhu Jin-Hua,Liu Bi-Cheng,Liu Hong
Background Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) represents a novel therapeutic approach for renal anemia, a prevalent complication of chronic kidney disease (CKD). However, the effects of HIF-PHI on renal functional outcomes remain poorly characterized. Here, the potential effects of FG-4592, an orally administered HIF-PHI, on renal fibrosis were explored systematically. Methods In this study, a CKD rat model was established through subtotal 5/6 nephrectomy. Rats were administered either FG-4592 or vehicle control via oral gavage three times weekly for 12 consecutive weeks. Additionally, recombinant FGF23 was continuously delivered via subcutaneously implanted Alzet osmotic minipumps for 28 days. Results Interestingly, we found that CKD-induced anemia was significantly ameliorated in CKD rats with FG-4592 treatment. Meanwhile, markedly alleviated histopathological changes and renal tubulointerstitial fibrosis (TIF) were observed in rats with FG-4592 administration. Notably, serum levels of intact FGF23 (iFGF23) were significantly reduced following FG-4592 administration in CKD rats. This finding was subsequently validated in CKD patients receiving Roxadustat therapy. Mechanistically, we illustrated that inhibition of the iFGF23-WNT5A pathway was the exact mechanism by which FG-4592 ameliorated TIF. Further, we also demonstrated that transcriptional activation of Furin enzyme was the exact molecular mechanism for FG-4592-mediated iFGF23 cleavage. Conclusions FG-4592 attenuates TIF through Furin-mediated proteolytic cleavage of iFGF23. These findings provide novel mechanistic insights into HIF-PHI-mediated renal protection and establish a theoretical framework for clinical translation.
研究领域:
肾脏病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Huijie Lv,Siqi Luo,Ruochen Tian,Wenhua Zhang,Baoshan Sun,Yan Cui
Epinephrine and norepinephrine are a class of chiral endogenous catecholamines, which are known as major neurotransmitters. This work described a new LC–MS/MS method coupled with pre-column derivatization, enabling the simultaneous enantiomeric separation of epinephrine and norepinephrine in rat plasma. After protein precipitation procedure, the samples were derivatized with ( S )-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester, [( S )-NIFE]. The derivatives resolved with good baseline separation on an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with mobile phase composed of methanol with 0.2% formic acid in water at a flow rate of 0.2 mL/min. Analysis was performed by multiple reaction monitoring in positive ionization mode. The linear ranges were 1.0–500 ng/mL for epinephrine enantiomers and 1.5–750 ng/mL for norepinephrine enantiomers. The lower limits of quantification for epinephrine and norepinephrine enantiomers were 1.0 and 1.5 ng/mL, respectively. The intra-day and inter-day precision were all less than 10.7% and accuracy ranged from 96.0 to 101.5%. Recoveries for all the analytes were more than 80.3%. The proposed method was successfully applied to simultaneously determine endogenous epinephrine and norepinephrine enantiomers in rat plasma. l -epinephrine and l -norepinephrine were sensitively and accurately quantified while both the d -enantiomers were not detected. Additionally, epinephrine enantiomers were analyzed for stereoselective pharmacokinetics in rats after intravenous administration of racemic epinephrine for the first time. The pharmacokinetic results indicated that the disposition of epinephrine enantiomers was stereoselective and chiral inversion did not occur in rats.
研究领域:
分析化学
·
药物代谢
·
神经生物学
✓ 已验证
DOI
高影响因子
Communications Biology
·
2025
·Vol. 8
·期 1
·1-12
·
IF 5.1
Yuan Xingyue,Li Ya,Cong Lin,Yang Lingling,Zhang Yangyang,Zhang Zhenzhen,Wang Ting,Dong Muchen,Du Xianli,Xie Lixin,Zhou Qingjun
Norepinephrine (NE) is mainly released by sympathetic nerve terminals to act on organs and tissues. After corneal epithelial debridement, we found that the sympathetic nerve fibers penetrated the limbus and regenerated toward the cornea within 24 h post-wounding. Topical NE application recapitulated the characteristics of delayed corneal epithelial wound healing and nerve regeneration in healthy mice, accompanied by the partial depletion of multiple neurotrophins, such as nerve growth factor and glial cell-derived nerve growth factor. Moreover, the diabetes mellitus (DM) mice exhibited corneal sensory nerve dysfunction and increased plasma and corneal NE contents, which were rescued by 6-hydroxydopamine (6-OHDA) and bretylium. In the cell culture model, the conditioned medium of NE-treated corneal epithelial cells inhibited trigeminal ganglion (TG) neurite outgrowth, which was reversed by the β2 adrenergic receptor (ADRB2) antagonist, but not by the β1 adrenergic receptor (ADRB1) antagonist. Topical application of the ADRB2 antagonist recovered the expression of corneal neurotrophins, and promoted corneal epithelial and nerve regeneration in DM mice. Taken together, the NE-ADRB2 axis regulates corneal neurotrophin expression and nerve regeneration in mice. Topical application of the ADRB2 antagonist may represent a promising therapeutic strategy for diabetic corneal sensory nerve dysfunction.
研究领域:
神经生物学
·
眼科
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
PHYSIOLOGICAL RESEARCH
·
2024
·Vol. 73
·期 5
·779
·
IF 1.9
Lu BAI,Qian CHEN,Yanqing LI,Fen WU,Mingzhe JIN,Yuhong CHEN,Xu TENG,Sheng JIN,Huanfang FAN,Yuming WU
Trimethylamine N-oxide (TMAO), a bioactive metabolite of gut microbes, plays a pivotal role in the pathogenesis of kidney diseases by activating programmed cell death (PCD) pathways. However, whether trimethylamine (TMA) contributes to chronic kidney injury and which kind of PCD is involved in TMA-induced chronic kidney injury has not been previously evaluated. To observe the effect of TMA, male C57BL/6J mice were randomly divided into two groups: the Control group and the TMA group. The mice in the TMA group were intraperitoneally injected with 100 μmol/kg/day TMA for three months, whereas the mice in the Control group were injected with normal saline for the same period. After three months, plasma creatinine and blood urea nitrogen levels, indicators of kidney function, increased significantly in the TMA group as compared with those in the Control group. Furthermore, Masson staining assay showed that TMA treatment led to a larger area of fibrosis than the Control group. TMA treatment did not change the Bax/Bcl-2 ratio, RIP1, RIP3 and MLKL phosphorylation, or iron and malondialdehyde levels in kidney tissues, indicating that apoptosis, ferroptosis and necroptosis were not involved in TMA-induced chronic kidney injury. However, compared with the Control group, TMA treatment significantly upregulated NLRP3, Caspase-1, IL-1β, cleaved-Caspase 8, Caspase-8, and ZBP1 protein expression in kidney tissues. These results indicated that the ZBP1-NLRP3 inflammasome pathway was involved in TMA-induced chronic kidney injury. In conclusion, our studies revealed that the ZBP1-NLRP3 inflammasome may take part in the progression of TMA induced chronic kidney injury.
研究领域:
肾脏病学
·
免疫学
·
微生物学
·
分子生物学
·
病理学
✓ 已验证
DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2019
·Vol. 176
·期 14
·2627-2641
·
IF 6.583
Zheng Xu,Chunpeng Zou,Weihui Yu,Sujing Xu,Lan Huang,Zia Khan,Jingying Wang,Guang Liang,Yi Wang
Background and Purpose Hypertension adversely affects the kidney and is the second leading cause of kidney failure. Overproduction of angiotensin II greatly contributes to the progression of hypertensive kidney disease. Angiotensin II has recently been shown to activate STAT3 in cardiovascular cells. However, the underlying mechanisms of STAT3 activation by angiotensin II and downstream functional consequences in the kidneys are not fully understood. Experimental Approach C57BL/6 mice were treated with angiotensin II by subcutaneous infusion for 1 month to develop nephropathy. Mice were treated with either adeno-associated virus expressing STAT3 shRNA or STAT3 inhibitor, S3I-201. Human archival kidney samples from five patients with hypertension and five individuals without hypertension were also examined. In vitro, STAT3 was blocked using siRNA or STAT3 inhibitor S3I-201 in the renal proximal tubular cell line, NRK52E, after exposure to angiotensin II. Key Results Angiotensin II activated STAT3 in kidney epithelial cells through engaging toll-like receptor 4 (TLR4) and JAK2, which was independent of IL-6/gp130 and angiotensin AT 1 receptors. Angiotensin II-mediated STAT3 activation increased fibrotic proteins and resulted in renal dysfunction. Both STAT3 inhibition by the low MW compound S3I-201 and TLR4 deficiency normalized renal fibrosis and dysfunction caused by Ang II in mice, without affecting hypertension. Conclusions and Implications Our study reveals a novel mechanism of STAT3 activation, induced by angiotensin II, in kidney tissues and highlights a translational significance of a STAT3 inhibitor as potential therapeutic agent for hypertensive kidney disease.
研究领域:
肾病学
·
药理学
·
分子生物学
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Gao Ping,Du Xiaoyi,Liu Lili,Xu Hua,Liu Maochang,Guan Xinlei,Zhang Chengliang
Tacrolimus-induced chronic nephrotoxicity (TIN) hinders its long-term use in patients. However, there are no drugs available in the clinic to relieve it at present. Astragaloside IV (AS-IV) is a saponin extract of the Astragalus which is widely used in the treatment of kidney disease. This study aimed to investigate the effect of AS-IV on TIN and its underlying mechanism. Herein, C57BL/6 mice were treated with tacrolimus and/or AS-IV for 4 weeks, and then the renal function, fibrosis, oxidative stress and p62-Keap1-Nrf2 pathway were evaluated to ascertain the contribution of AS-IV and p62-Keap1-Nrf2 pathway to TIN. Our results demonstrated that AS-IV significantly improved renal function and alleviated tubulointerstitial fibrosis compared with the model group. The expression of fibrosis-related proteins, including TGF-β1, Collagen I and α-SMA, were also decreased by AS-IV. Furthermore, AS-IV relieved the inhibition of tacrolimus on antioxidant enzymes. The data in HK-2 cells also proved that AS-IV reduced tacrolimus-induced cell death and oxidative stress. Mechanistically, AS-IV markedly promoted the nuclear translocation of Nrf2 and the renal protective effects of AS-IV were abolished by Nrf2 inhibitor. Further researches showed that phosphorylated p62 was significantly increased after AS-IV pretreatment. Moreover, AS-IV failed to increase nuclear translocation of Nrf2 and subsequent anti-oxidative stress in HK-2 cells transfected with p62 siRNA. Collectively, these findings indicate that AS-IV relieve TIN by enhancing p62 phosphorylation, thereby increasing Nrf2 nuclear translocation, and then alleviating ROS accumulation and renal fibrosis.
研究领域:
药理学
·
肾病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）