27 December 2002
Agonists of peroxisome-proliferator activated receptor-α (clofibrate and WY14643) reduce renal ischemia/reperfusion injury in the rat.
Ahila Sivarajah, Prabal K. Chatterjee, Yoshiyuki Hattori, Paul AJ. Brown, Keith N. Stewart, Zoran Todorovic, Helder Mota-Filipe, Christoph ThiemermannMed Sci Monit 2002; 8(12): BR532-539 :: ID: 4815
Abstract
BACKGROUND: The aim of this study was to investigate the effects of peroxisome-proliferator activated receptor-alpha (PPAR-alpha) agonists, clofibrate and WY14643 on the renal dysfunction and injury caused by bilateral ischemia/reperfusion (I/R) of rat kidneys in vivo. MATERIAL/METHODS: Male Wistar rats were anesthetized with sodium thiopentone (120 mg/kg i.v.) and subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h). Serum and urinary biochemical indicators of renal dysfunction and injury were measured; serum creatinine (sCr, glomerular dysfunction), fractional excretion of Na+ (FENa, tubular dysfunction), and urinary N-acetyl-b-D-glucosaminidase (uNAG, tubular injury). Additionally, renal sections were used for histological grading of renal injury and for RT-PCR analysis of the expression of PPAR-isoforms in kidneys obtained from rats prior to or after I/R. In addition, expression of intercellular adhesion molecule-1 (ICAM-1) was determined using Northern blot analysis. RESULTS: Using RT-PCR, we document here the expression of PPAR-alpha, PPAR-beta and PPAR-gamma1 (but not PPAR-gamma2) in the kidney of the rat. I/R resulted in the down-regulation of PPAR-alpha without modulation of any other PPAR. Clofibrate and WY14643 significantly reduced the increases in sCr, FENa and uNAG caused by renal I/R, indicating attenuation of renal dysfunction and injury. Expression of ICAM-1 caused by I/R of the kidney was not modulated by PPAR-alpha agonists. CONCLUSIONS: We show here that (i) renal I/R results in the down-regulation of PPAR-alpha in the kidney, and (ii) that the PPAR-alpha agonists clofibrate and WY14643 reduce the renal dysfunction and injury associated with I/R of the kidney.
Keywords: Clofibrate - pharmacology, Reperfusion Injury - genetics
Editorial
01 July 2022 : Editorial
Editorial: World Health Organization (WHO) Variants of Concern Lineages Under Monitoring (VOC-LUM) in Response to the Global Spread of Lineages and Sublineages of Omicron, or B.1.1.529, SARS-CoV-2DOI: 10.12659/MSM.937676
Med Sci Monit 2022; 28:e937676
SARS-CoV-2/COVID-19
27 June 2022 : Clinical Research
Shoulder Injury Related to Vaccine Administration (SIRVA) in 16 Patients Following COVID-19 Vaccination Who...Med Sci Monit In Press; DOI: 10.12659/MSM.937430
04 June 2022 : Clinical Research
Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...Med Sci Monit 2022; 28:e936962
30 May 2022 : Clinical Research
Effects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...Med Sci Monit 2022; 28:e936069
27 May 2022 : Clinical Research
Factors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)Med Sci Monit 2022; 28:e936547
In Press
01 Jul 2022 : Clinical Research
Does Early-Period Patient Dissatisfaction Turn Into Satisfaction Over Time After Total Knee Replacement?Med Sci Monit In Press; DOI: 10.12659/MSM.936792
30 Jun 2022 : Laboratory Research
Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human...Med Sci Monit In Press; DOI: 10.12659/MSM.936760
30 Jun 2022 : Clinical Research
Antioxidant System and Ions Concentrations After Femoral Neck and Resurfacing Hip ArthroplastyMed Sci Monit In Press; DOI: 10.12659/MSM.936335
28 Jun 2022 : Meta-Analysis
Urodynamics in Early Diagnosis of Diabetic Bladder Dysfunction in Women: A Systematic Review and Meta-AnalysisMed Sci Monit In Press; DOI: 10.12659/MSM.937166
Most Viewed Current Articles
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292
01 Nov 2020 : Review article
Long-Term Respiratory and Neurological Sequelae of COVID-19DOI :10.12659/MSM.928996
Med Sci Monit 2020; 26:e928996
13 Nov 2021 : Clinical Research
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788