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Boldine provides protective effect against nephrotoxicity induced by cisplatin in Wistar rats:Role of oxidative stress,inflammation and caspase-3

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BIOCELL 2022年第9期46卷 2111-2122页

作者： NERGIZ HACER TURGUT HUSEYIN GUNGOR MEHMET EKICI MUMIN ALPER ERDOGAN MEHMET ONDER KARAYIGIT HAKI KARA Department of Pharmacology Faculty of PharmacyIzmir Katip Celebi UniversityIzmir35620Turkey Department of Pharmacology and Toxicology Faculty of Veterinary MedicineCumhuriyet UniversitySivas58140Turkey Department of Physiology Faculty of Veterinary MedicineCumhuriyet UniversitySivas58140Turkey Department of Physiology Faculty of MedicineIzmir Katip Celebi UniversityIzmir35620Turkey Department of Pathology Faculty of Veterinary MedicineCumhuriyet UniversitySivas58140Turkey

Side effects of cisplatin,especially dose-dependent nephrotoxicity,are major factors limiting its use in ***((S)-2,9-dihydroxy-1,10-dimethoxy-aporphine)is a natural alkaloid known for its strong antioxidant activity present in leaves/bark of boldo tree(Peumus boldus Molina),a native tree in ***,we aimed to investigate the nephroprotective effect of boldine and its underlying mechanisms on cisplatin-induced rat renal *** Wistar albino rats divided into 5 groups(Control,Cis,Bold.40,Cis+Bold.20,Cis+Bold.40 groups)were *** received boldine(20 or 40 mg/kg/day),or vehicle(saline)intraperitoneal for 14 days and a single dose cisplatin(7 mg/kg,ip)was applied on the 10th day to induce *** and kidney tissue were weighed to determine kidney *** urea nitrojen(BUN)and creatinine levels,the amount of thiobarbituric acid reactive substances(TBARS,an index of lipid peroxidation),superoxide dismutase(SOD),glutathione peroxidase(GPx)enzyme activities and tumor necrosis factor alpha(TNF-α)levels were measured and histopathologic examination was *** nitric oxide synthase(iNOS)and caspase-3 expressions were detected *** induced by cisplatin was apparent by elevated levels of BUN,creatinine,kidney index,TBARS and TNF-α,and decreased body weight,SOD and GPx enzyme *** with boldine protected the renal function at both boldine doses by fixing the renal damage markers,oxidative stress,caspase-3 and iNOS *** findings supported biochemical *** together these findings indicate that boldine has promising protective effect against cisplatin nephrotoxicity by improving oxidative stress,inflammation,histopathological alterations and by alleviating caspase 3 expression.

关键词： Boldine Caspase-3 cisplatin nephrotoxicity Inflammation Oxidative stress

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Plasmacytoid dendritic cells promote acute kidney injury by producing interferon-α

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Cellular & Molecular Immunology 2021年第1期18卷 219-229页

作者： Bo Deng Yuli Lin Yusheng Chen Shuai Ma Qian Cai Wenji Wang Bingji Li Tingyan Liu Peihui Zhou Rui He Feng Ding Division of Nephrology Shanghai Ninth Peopled HospitalSchool of MedicineShanghai Jiaotong University200011 ShanghaiChina Department of Immunology and Key Laboratory of Medical Molecular Virology of Ministries of Education and Health School of Basic Medical SciencesFudan University200032 ShanghaiChina Institutes of Integrative Medicine Fudan University200032 ShanghaiChina Department of Gastrointestinal Surgery Shanghai Pudong HospitalFudan University Pudong Medical Center200120 ShanghaiChina

Acute kidney injury(AKI)is a common clinical complication associated with high mortality in *** cells and cytokines have recently been described to play essential roles in AKI *** dendritic cells(pDCs)are a unique DC subset that specializes in type Ⅰ interferon(IFN)***,we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α.Deletion of pDCs using DTR^(BDCA2) transgenic(Tg)mice suppressed cisplatin-induced AKI,accompanied by marked reductions in proinflammatory cytokine production,immune cell infiltration and apoptosis in the *** contrast,adoptive transfer of pDCs during AKI exacerbated kidney *** further identified IFN-α as the key factor that mediated the functions of pDCs during AKI,as IFN-α neutralization significantly attenuated kidney ***,IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells(TECs)in *** addition,our data demonstrated that apoptotic TECs induced the activation of pDCs,which was inhibited in the presence of an apoptosis ***,similar deleterious effects of pDCs were observed in an ischemia reperfusion(IR)-induced AKI ***,increased expression of IFN-α in kidney biopsies was observed in kidney transplants with *** together,the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.

关键词： acute kidney injury cisplatin nephrotoxicity plasmacytoid dendritic cells interferon-α

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