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Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria

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World Journal of Clinical Cases 2024年第13期12卷 2173-2181页

作者： Hai-Chang Xu Yan Cui Xue-Ying Wang Hai-Bo Wu Wei Li Dan Wang Na Lin Lin Lin Ying-Hui Zhang Department of Intensive Care Medicine The General Hospital of the Northern Theater Command of the People's Liberation Army of ChinaShenyang 110016Liaoning ProvinceChina

BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there we

关键词： Colistin sulfate Extensively drug-resistant Pneumonia Intravenous combined with nebulization Sepsis nephrotoxicity Neurotoxicity

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Schisandra chinensis Oil Attenuates Aristolochic Acid Ⅰ-Induced nephrotoxicity in vivo and in vitro

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Chinese Journal of Integrative Medicine 2022年第7期28卷 603-611页

作者： YANG Yan GE Fei-lin ZHAN Xiao-yan MU Wen-qing LI Zhi-yong LIN Li WEI Zi-ying BAI Zhao-fang SUN Qin XIAO Xiao-he School of Integrated Traditional Chinese and Western Medicine Southwest Medical UniversityLuzhouSichuan Province 646000China Senior Department of Hepatology the Fifth Medical Center of PLA General HospitalBeijing 100039China China Military Institute of Chinese Materia the Fifth Medical Center of PLA General HospitalBeijing 100039China

Objective: To investigate the protective effects of Schisandra chinensis oil(SCEO) against aristolochic acid Ⅰ(AAⅠ)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism.Methods: C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AAⅠ group, and AAⅠ+SCEO(0.25, 0.5 and 1 g/kg) groups(n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AAⅠ groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AAⅠ(5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling(TUNEL) staining, respectively. The levels of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), and serum creatinine(SCr), as well as renal malondialdehyde(MDA), glutathione, r-glutamyl cysteingl+glycine(GSH), and superoxide dismutase(SOD) were analyzed using enzyme-linked immunosorbent assay(ELISA).Expressions of hepatic cytochrome P450 1A1(CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1(NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction(qPCR) and Western blot,respectively. In vitro, SCEO(40 μg/mL) was added 12 h before treatment with AAⅠ(40 μmol/mL for 48 h) in human renal proximal tubule cell line(HK-2), then apoptosis and reactive oxygen species(ROS) were analyzed by flow cytometry. Results: SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AAⅠ-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr(P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA,GSH and SOD(P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues(P<0.01 or P<0.05). Besides, in vitro studies

关键词： aristolochic acidⅠ nephrotoxicity Schisandra chinensis oil metabolic enzymes apoptosis reactive oxygen species

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Prevalence of polymyxin-induced nephrotoxicity and its predictors in critically ill adult patients:A meta-analysis

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World Journal of Clinical Cases 2022年第31期10卷 11466-11485页

作者： Jiang-Lin Wang Bi-Xiao Xiang Xiao-Li Song Rui-Man Que Xiao-Cong Zuo Yue-Liang Xie Department of Pharmacy The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina Department of Pharmacy Sanya Central HospitalSanya 572000Hainan ProvinceChina

BACKGROUND Polymyxin-induced nephrotoxicity is a major safety concern in clinical practice due to long-term adverse outcomes and high mortality.AIM To conducted a systematic review and meta-analysis of the prevalence and potential predictors of polymyxin-induced nephrotoxicity in adult intensive care unit(ICU)patients.METHODS PubMed,EMBASE,the Cochrane Library and Reference Citation Analysis database were searched for relevant studies from inception through May 30,2022.The pooled prevalence of polymyxin-induced nephrotoxicity and pooled risk ratios of associated factors were analysed using a random-effects or fixed-effects model by Stata SE ver.12.1.Additionally,subgroup analyses and meta-regression were conducted to assess heterogeneity.RESULTS A total of 89 studies involving 12234 critically ill adult patients were included in the meta-analysis.The overall pooled incidence of polymyxin-induced nephrotoxicity was 34.8%.The pooled prevalence of colistin-induced nephrotoxicity was not higher than that of polymyxin B(PMB)-induced nephrotoxicity.The subgroup analyses showed that nephrotoxicity was significantly associated with dosing interval,nephrotoxicity criteria,age,publication year,study quality and sample size,which were confirmed in the univariable meta-regression analysis.nephrotoxicity was significantly increased when the total daily dose was divided into 2 doses but not 3 or 4 doses.Furthermore,older age,the presence of sepsis or septic shock,hypoalbuminemia,and concomitant vancomycin or vasopressor use were independent risk factors for polymyxin-induced nephrotoxicity,while an elevated baseline glomerular filtration rate was a protective factor against colistin-induced nephrotoxicity.CONCLUSION Our findings indicated that the incidence of polymyxin-induced nephrotoxicity among ICU patients was high.It emphasizes the importance of additional efforts to manage ICU patients receiving polymyxins to decrease the risk of adverse outcomes.

关键词： Polymyxins nephrotoxicity Critically ill adult patients Risk factors Meta-analysis

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In vitro study of emodin-induced nephrotoxicity in human renal glomerular endothelial cells on a microfluidic chip

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BIOCELL 2023年第1期47卷 125-131页

作者： ZHUO YANG WEN QIN DI CHEN JUNSHENG HUO JINGBO WANG LIYUAN WANG QIN ZHUO JIYONG YIN National Institute for Nutrition and Health Chinese Center for Disease Control and PreventionBeijing100050China

Emodin is an effective component of rhubarb with positive pharmacological effects on human health.However,it is also toxic to different cells or tissues to varying degrees.The effects of emodin on glomerular endothelial cells(GECs)remain to be tested,and the documented works were always performed in vitro and hardly reflect the real physiological situation.To study the effects of emodin on GECs in a biomimetic environment,we utilized a microfluidic chip to assess the physiological reaction of human renal glomerular endothelial cells to various concentrations of emodin in this work.The results showed that emodin caused cytotoxicity,impaired glomerular filtration barrier integrity to macromolecules,and increased barrier permeability in a dose-dependent manner.With the increase in emodin concentration,the concentration of the pro-inflammatory cytokine tumor necrosis factor-α,interleukin(IL)-6,transforming growth factor-β1,and monocyte chemoattractant protein(MCP-1)increased while the production of inflammatory cytokine IL-6 first increased and then decreased with the increase in emodin concentration.Our findings shed new light on emodin-induced nephrotoxicity and provide insights for the application of microfluidic chip devices to reveal drug-cell interactions.

关键词： Emodin nephrotoxicity HRGECs Microfluidic chip

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Melatonin alleviates oxidative stress,inflammation,apoptosis,and DNA damage in acrylamide-induced nephrotoxicity in rats

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Asian Pacific Journal of Tropical Biomedicine 2023年第3期13卷 121-130页

作者： Fatmaİbaokurgil Hakan Aydin Serkan Yildirim Emin Sengul Department of Physiology Faculty of Veterinary MedicineAtatürk UniversityErzurumTurkey Department of Virology Faculty of Veterinary MedicineAtatürk UniversityErzurumTurkey Department of Pathology Faculty of Veterinary MedicineAtatürk UniversityErzurumTurkey

Objective:To investigate the effects of melatonin on renal inflammation,oxidative stress,apoptosis,as well as DNA and tissue damage in acrylamide-induced nephrotoxicity in rats.Methods:Fifty male rats were randomly divided into five groups.The control group received distilled water by gastric lavage for 11days and the acrylamide group was administered acrylamide(50 mg/kg,i.g.)for 11 days.The MEL10+ACR and MEL20+ACR groups received intraperitoneal melatonin 10 and 20 mg/kg,respectively,for 11 days,and acrylamide(50 mg/kg,i.g.)was administered 1h after melatonin injection.The MEL20 group was injected with melatonin(20 mg/kg)for 11 days.Kidney function tests were performed and biochemical and inflammatory parameters were determined.In addition,histopathological,immunohistochemical,and immunofluorescence examinations were carried out.Results:Melatonin significantly abated acrylamide-induced rise in serum urea and creatinine levels.Acrylamide caused oxidative stress,inflammation,apoptosis,as well as DNA and tissue damage in the kidneys.Melatonin treatment alleviated acrylamide-induced renal damage by exhibiting antioxidant,anti-inflammatory,and antiapoptotic effects.Moreover,melatonin significantly ameliorated acrylamide-caused histopathological changes in kidney tissue.Conclusions:Melatonin attenuates acrylamide-induced renal oxidative stress,inflammation,apoptosis,and DNA damage in rats.

关键词： Acrylamide Apoptosis Inflammation Melatonin nephrotoxicity Oxidative stress Rat

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Naringin attenuates oxidative stress,inflammation,apoptosis,and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats

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Asian Pacific Journal of Tropical Biomedicine 2022年第5期12卷 223-232页

作者： Volkan Gelen Serkan Yıldırım EminŞengül AliÇınar FikretÇelebi Merve Küçükkalem Melahat Gök Department of Physiology Faculty of Veterinary MedicineKafkas UniversityKarsTurkey Department of Pathology Faculty of Veterinary MedicineAtatürk UniversityErzurumTurkey Department of Physiology Faculty of Veterinary MedicineAtatürk UniversityErzurumTurkey

Objective:To explore the possible effects of naringin on acrylamide-induced nephrotoxicity in rats.Methods:Sprague-Dawley rats weighing 200-250 g were randomly divided into five groups.The control group was given intragastric(i.g.)saline(1 mL)for 10 d.The acrylamide group was given i.***.acrylamide in saline(38.27 mg/kg titrated to 1 mL)for 10 d.The treatment groups were administered with naringin in saline(50 and 100 mg/kg,respectively)for 10 d and given i.***.acrylamide(38.27 mg/kg)1 h after naringin injection.The naringin group was given i.***.naringin(100 mg/kg)alone for 10 d.On day 11,intracardiac blood samples were obtained from the rats when they were under anesthesia,after which they were euthanized.Urea and creatinine concentrations of blood serum samples were analyzed with an autoanalyzer.Enzyme-linked immunosorbent assay was used to quantify malondialdehyde,superoxide dismutase,glutathione,glutathione peroxidase,catalase,tumor necrosis factor-α,nuclear factor-κB,interleukin(IL)-33,IL-6,IL-1β,cyclooxygenase-2,kidney injury molecule-1,mitogen-activated protein kinase-1,and caspase-3 in kidney tissues.Renal tissues were also evaluated by histopathological and immunohistochemical examinations for 8-OHdG and Bcl-2.Results:Naringin attenuated acrylamide-induced nephrotoxicity by significantly decreasing serum urea and creatinine levels.Naringin increased superoxide dismutase,glutathione,glutathione peroxidase,and catalase activities and decreased malondialdehyde levels in kidney tissues.In addition,naringin reduced the levels of inflammatory and apoptotic parameters in kidney tissues.The histopathological assay showed that acrylamide caused histopathological changes and DNA damage,which were ameliorated by naringin.Conclusions:Naringin attenuated inflammation,apoptosis,oxidative stress,and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats.

关键词： Acrylamide nephrotoxicity Apoptosis Inflammation Naringin Oxidative stress Oxidative DNA damage

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The natural sources,extraction,and nephroprotective function of oleanolic acid and ursolic acid:a review

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Food and Health 2024年第3期6卷 20-32页

作者： Wen-Ying Chen Hong-Wei Wang Song Yao Yao Zhou Shuang-Chao Liu Xiao Li Shen School of Public Health Zunyi Medical UniversityZunyi 563000GuizhouChina Key Laboratory of Maternal&Child Health and Exposure Science of Guizhou Higher Education Institutes Zunyi 563000GuizhouChina

Oleanolic acid(OA)and ursolic acid(UA)are commonly present in the cuticular wax of many edible fruits and medicinal herbs.OA and UA belong to the group of bioactive pentacyclic triterpenoids,exhibiting a wide range of beneficial effects including protection for the kidneys,liver,heart,gastrointestinal tract,and spinal cord.Additionally,OA and UA exhibit antioxidant,anti-ferroptotic,anti-apoptotic,anti-inflammatory,anti-tumor,anti-viral,anti-diabetic,anti-microbial,anti-parasitic,analgesic,wound-healing,hypolipidemic,and hypoglycemic properties,often without notable side effects.Due to the extensive array of their positive functions,it is not feasible to thoroughly cover all aspects in this review.Therefore,the primary focus lies on reviewing the natural sources,extraction,and nephroprotective properties of OA and UA.To summarize,current literatures highlight the nephroprotective mechanisms of OA and UA,primarily involving inhibiting oxidative stress,endoplasmic reticulum stress,glycative stress,dyslipidemia,inflammation,apoptosis,pyroptosis,and renal fibrosis,promoting diuresis,as well as fine-tuning autophagy.

关键词： oleanolic acid ursolic acid natural sources nephroprotective nephrotoxicity

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Protective effect of Cistanche deserticola on gentamicin-induced nephrotoxicity in rats

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Chinese Herbal Medicines 2023年第1期15卷 102-109页

作者： Xiaoqing Song Jinying Wang Yu Zhang Xinqian Du Qibing Qian Basic Medical College of Hebei North University Zhangjiakou 075000China

Objective: Gentamicin(GM) is a commonly used aminoglycoside antibiotic, however, renal toxicity has limited its usage. The present study was designed to evaluate the ameliorative effect of Cistanche deserticola on GM-induced nephrotoxicity in rats.Methods: The nephrotoxicity in rats was induced by intraperitoneal administration of GM(100 mg/kg)for 10 consecutive days. Glomerular filtration rate, blood urea nitrogen, creatinine and kidney histopathology were detected to assess the GM-induced nephrotoxicity. The oxidative stress(catalase,superoxide dismutase, glutathione and malondialdehyde) was assessed. The inflammatory response(tumor necrosis factor-a, interleukin-6, myeloperoxidase and nuclear factor-kappa B) and apoptotic marker(Bax and Bcl-2) were also evaluated.Results: The results showed that water and 75% ethanol extracts of C. deserticola(named CDW and CDE,respectively)(100, 200 and 400 mg/kg) in combination with GM could recover the reduction of glomerular filtration rate and enhance the renal endogenous antioxidant capability induced by GM. The increase in the expression of renal inflammatory cytokines(tumor necrosis factor-a and interleukin-6), nuclear protein of nuclear factor-kappa B(p65) and the activity of myeloperoxidase induced by GM was significantly decreased upon CDW or CDE treatment. In addition, CDW or CDE treatment could decrease the Bax protein expression and increase the Bcl-2 protein expression in GM-induced nephrotoxicity in rats significantly.Conclusion: The study demonstrated that C. deserticola treatment could attenuate kidney dysfunction and structural damage in rats induced by GM through the reduction of inflammation, oxidative stress and apoptosis.

关键词： apoptosis Cistanche deserticola Y.C.Ma gentamicin inflammation nephrotoxicity Orobanchaceae oxidative stress

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Melamine nephrotoxicity is Mediated by Hyperuricemia

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Biomedical and Environmental Sciences 2015年第12期28卷 904-912页

作者： ZHANG Long LI Hong Tian WANG Lin Lin TRACHTMAN Howard TRASANDE Leonardo WANG Pei Xin LIU Jian Meng Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health Peking University Health Science Center Department of Epidemiology and Health Statistics School of Public HealthPeking University Health Science Center Departments of Pediatrics Environmental Medicine and Population HealthNew York University School of Medicine NYU Wagner School of Public Service NYU Steinhardt School of Culture Education and Human Development

Objective We tested whether melamine nephrotoxicity was exacerbated by urate(a typical component of renal stones in humans)in rats with hyperuricemiainduced by the uricase inhibitor,potassium oxonate(Oxo).Methods Rats were exposed to melamine or Oxo alone or combinations of melamine(200-400 mg/kg)and Oxo(200-600 mg/kg)for 3 consecutive days.Kidney injury was evaluated by renal biochemical functions,histomorphology,and lipid peroxidation.Kidney crystals were analyzed for their composition.Results nephrotoxicity was minimal in animals administered melamine or Oxo alone,but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined.All rats in the 400+600(melamine+Oxo)and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days;no rat died in the 200+400 or 200+200 mg/kg group.Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds.Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys,resembling human stones.Conclusion Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans.Future studies should consider uric acid together with melamine when examining adverse effects in humans.

关键词： Melamine nephrotoxicity Hyperuricemia Urolithiasis

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In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging

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Acta Pharmaceutica Sinica B 2020年第6期10卷 1083-1093页

作者： Zhonghua Wang Bingshu He Yaqi Liu Meiling Huo Wenqing Fu Chunyan Yang Jinfeng Wei Zeper Abliz Center for Imaging and Systems Biology College of Life and Environmental SciencesMinzu University of ChinaBeijing 100081China New Drug Safety Evaluation Center Institute of Materia MedicaPeking Union Medical CollegeBeijing 100050China Key Laboratory of Ethnomedicine of Ministry of Education Minzu University of ChinaBeijing 100081China School of Pharmacy Minzu University of ChinaBeijing 100081China

Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development.Herein,an in situ metabolomics method based on air flow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI)was established for direct analysis of metabolites in renal tissue sections.This method was subsequently applied to investigate spatially resolved metabolic profile changes in rat kidney after the administration of aristolochic acid I,a known nephrotoxic drug,aimed to discover metabolites associated with nephrotoxicity.As a result,38 metabolites related to the arginine-creatinine metabolic pathway,the urea cycle,the serine synthesis pathway,metabolism of lipids,choline,histamine,lysine,and adenosine triphosphate were significantly changed in the group treated with aristolochic acid I.These metabolites exhibited a unique distribution in rat kidney and a good spatial match with histopathological renal lesions.This study provides new insights into the mechanisms underlying aristolochic acids nephrotoxicity and demonstrates that AFADESI-MSI-based in situ metabolomics is a promising technique for investigation of the molecular mechanism of drug toxicity.

关键词： Aristolochic acid nephrotoxicity Mass spectrometry imaging In situ metabolomics AFADESI

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