دورية أكاديمية
أعرض في EDS

Immunosuppressive therapies attenuate paraquat-induced renal dysfunction by suppressing inflammatory responses and lipid peroxidation.

التفاصيل البيبلوغرافية
العنوان: Immunosuppressive therapies attenuate paraquat-induced renal dysfunction by suppressing inflammatory responses and lipid peroxidation.
المؤلفون: Yen TH; Department of Nephrology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Clinical Poison Center, Kidney Research Center, And Center for Tissue Engineering, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan., Chang CW; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan., Tsai HR; Department of Nephrology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Clinical Poison Center, Kidney Research Center, And Center for Tissue Engineering, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan., Fu JF; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Medical Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan., Yen HC; Department of Nephrology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: yen@mail.cgu.edu.tw.
المصدر: Free radical biology & medicine [Free Radic Biol Med] 2022 Oct; Vol. 191, pp. 249-260. Date of Electronic Publication: 2022 Aug 27.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 8709159 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4596 (Electronic) Linking ISSN: 08915849 NLM ISO Abbreviation: Free Radic Biol Med Subsets: MEDLINE
أسماء مطبوعة: Publication: Tarrytown, NY : Elsevier Science
Original Publication: New York : Pergamon, c1987-
مواضيع طبية MeSH: Acute Kidney Injury*/chemically induced , Acute Kidney Injury*/drug therapy , Paraquat*/toxicity, Albumins ; Animals ; Creatinine ; Cyclophosphamide/pharmacology ; Dexamethasone/pharmacology ; F2-Isoprostanes ; Immunosuppression Therapy ; Immunosuppressive Agents ; Inflammation Mediators ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Lipid Peroxidation ; Mice ; Nitrogen ; Toll-Like Receptor 4 ; Toll-Like Receptor 9 ; Urea
مستخلص: Although paraquat (PQ) induces oxidative damage and inflammatory responses in the lungs, the mechanism underlying PQ-induced acute kidney injury in patients is unclear. Immunosuppressive therapy with glucocorticoids and the immunosuppressant cyclophosphamide (CP) has been employed to treat patients with PQ poisoning. This study examined whether PQ could concurrently cause renal injury, inflammatory responses, and oxidative damage in the kidneys, and whether CP and dexamethasone (DEX) could suppress PQ-induced alterations. Mice were assigned to eight groups: Control, PQ, DEX, PQ plus DEX, CP, PQ plus CP, DEX plus CP, and PQ plus DEX with CP. DEX, CP, and DEX plus CP reversed PQ-induced renal injury, as indicated by urinary albumin-to-creatinine ratios and urea nitrogen levels in serum. The treatments also attenuated PQ-induced renal infiltration of leukocytes and macrophages and induction of the Il6, Tnf, Icam, Cxcl2, Tlr4, and Tlr9 genes encoding the inflammatory mediators in the kidneys. However, DEX only partially suppressed the macrophage infiltration, whereas DEX plus CP provided stronger protection than DEX or CP alone for the induction of Il6 and Cxcl2. Moreover, through the detection of F 2 -isoprostanes (F 2 -IsoPs) and isofurans in the kidneys and lungs and F 2 -IsoPs in the plasma and urine, the therapies were found to suppress PQ-induced lipid peroxidation, although DEX was less effective. Finally, PQ decreased ubiquinol-9:ubiquinone-9 ratios in the kidneys. This effect of PQ was not found under CP treatment, but the ratio was lower than that of the control group. Our findings suggest that the suppression of PQ-induced inflammatory responses by DEX and CP in the kidneys can mitigate oxidative damage and acute kidney injury.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Acute kidney injury; Cyclophosphamide; Dexamethasone; F(2)-isoprostanes; Inflammation; Isofurans; Lungs; Paraquat; Plasma; Ubiquinol; Urine
المشرفين على المادة: 0 (Albumins)
0 (F2-Isoprostanes)
0 (Immunosuppressive Agents)
0 (Inflammation Mediators)
0 (Interleukin-6)
0 (Toll-Like Receptor 4)
0 (Toll-Like Receptor 9)
7S5I7G3JQL (Dexamethasone)
8N3DW7272P (Cyclophosphamide)
8W8T17847W (Urea)
AYI8EX34EU (Creatinine)
N762921K75 (Nitrogen)
PLG39H7695 (Paraquat)
تواريخ الأحداث: Date Created: 20220828 Date Completed: 20221004 Latest Revision: 20221026
رمز التحديث: 20240829
DOI: 10.1016/j.freeradbiomed.2022.08.031
PMID: 36031164
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-4596
DOI:10.1016/j.freeradbiomed.2022.08.031