Regulator 1-Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Signaling Pathway in Investigating the Pathological Characteristics and Molecular Mechanism of Liver Cirrhosis Complicated by Acute Kidney Injury

2022 ◽  
Vol 12 (1) ◽  
pp. 112-120
Author(s):  
Jieqi Gong ◽  
Huanhua Lu
Keyword(s):  
Acute Kidney Injury ◽  
Liver Cirrhosis ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Kidney Injury ◽  
Male Rats ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Duct Ligation

The objective of this study was to investigate the molecular mechanism of the histopathological characteristics of liver cirrhosis (LC) complicated with acute kidney injury (AKI) and the signaling pathway of silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) during the pathogenesis of LC. 20 healthy male rats with AKI complicated by laparoscopic cholecystectomy were selected and divided randomly into control group (C group), lipopolysaccharide (LPS) group, bile duct ligation (BDL) group, and model group (lipopolysaccharide+BDL) (D group). The indexes of all the rats were determined, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), sarcoplasmic enzyme (Scr), and blood urea nitrogen (BUN); the SIRT1 and PGC-1α expressions in renal tissues of rats from each group was detected. Results showed that the AST and ALT levels in BDL group and D group were higher markedly than those before surgery (P < 0.05). The serum levels of Scr and BUN in D group 4 hours after LPS injection increased hugely compared with before injection (P < 0.05). Compared with BDL group, the protein levels of SIRT1 and PGC-1α in renal tissue of group D were decreased sharply (P < 0.05), and the SIRT1 protein expression was positively correlated with PGC-1α (r = 0.836 and P < 0.01). When LC were complicated with AKI, SIRT1 activity was reduced and PGC-1α expression was inhibited. Moreover, SIRT1-PGC-1α signaling pathway played a protective role in pathogenesis of LC complicated with AKI.

scholarly journals Blocking TGF-β Signaling Pathway Preserves Mitochondrial Proteostasis and Reduces Early Activation of PDGFRβ+ Pericytes in Aristolochic Acid Induced Acute Kidney Injury in Wistar Male Rats

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0157288 ◽  
Author(s):  
Agnieszka A. Pozdzik ◽  
Laetitia Giordano ◽  
Gang Li ◽  
Marie-Hélène Antoine ◽  
Nathalie Quellard ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Aristolochic Acid ◽  
Kidney Injury ◽  
Male Rats ◽  
Early Activation ◽  
Wistar Male Rats

scholarly journals PGC1α in the kidney

2018 ◽  
Vol 314 (1) ◽  
pp. F1-F8 ◽  
Author(s):  
Matthew R. Lynch ◽  
Mei T. Tran ◽  
Samir M. Parikh
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Diabetic Kidney Disease ◽  
Kidney Injury ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Relationship ◽  
Prime Target

Acute kidney injury (AKI) arising from diverse etiologies is characterized by mitochondrial dysfunction. The peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC1α), a master regulator of mitochondrial biogenesis, has been shown to be protective in AKI. Interestingly, reduction of PGC1α has also been implicated in the development of diabetic kidney disease and renal fibrosis. The beneficial renal effects of PGC1α make it a prime target for therapeutics aimed at ameliorating AKI, forms of chronic kidney disease (CKD), and their intersection. This review summarizes the current literature on the relationship between renal health and PGC1α and proposes areas of future interest.

scholarly journals (–)-Epicatechin is associated with increased angiogenic and mitochondrial signalling in the hindlimb of rats selectively bred for innate low running capacity

2013 ◽  
Vol 124 (11) ◽  
pp. 663-674 ◽  
Author(s):  
Maik Hüttemann ◽  
Icksoo Lee ◽  
Guy A. Perkins ◽  
Steven L. Britton ◽  
Lauren G. Koch ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Mitogen Activated Protein Kinase ◽  
Male Rats ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
In Vitro Experiments ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitogen Activated Protein

Alternative approaches to reduce congenital muscle dysfunction are needed in cases where the ability to exercise is limited. (−)-Epicatechin is found in cocoa and may stimulate capillarity and mitochondrial proliferation in skeletal muscle. A total of 21 male rats bred for LCR (low running capacity) from generation 28 were randomized into three groups: vehicle for 30 days (control); (−)-epicatechin for 30 days; and (−)-epicatechin for 30 days followed by 15 days without (−)-epicatechin. Groups 2 and 3 received 1.0 mg of (−)-epicatechin/kg of body mass twice daily, whereas water was given to the control group. The plantaris muscle was harvested for protein and morphometric analyses. In addition, in vitro experiments were conducted to examine the role of (−)-epicatechin on mitochondrial respiratory kinetics at different incubation periods. Treatment for 30 days with (−)-epicatechin increased capillarity (P<0.001) and was associated with increases in protein expression of VEGF (vascular endothelial growth factor)-A with a concomitant decrease in TSP-1 (thrombospondin-1) and its receptor, which remained after 15 days of (−)-epicatechin cessation. Analyses of the p38 MAPK (mitogen-activated protein kinase) signalling pathway indicated an associated increase in phosphorylation of MKK3/6 (MAPK kinase 3/6) and p38 and increased protein expression of MEF2A (myocyte enhancer factor 2A). In addition, we observed significant increases in protein expression of PGC-1α (peroxisome-proliferator-activated receptor γ co-activator 1α), PGC-1β, Tfam and cristae abundance. Interestingly, these increases associated with (−)-epicatechin treatment remained after 15 days of cessation. Lastly, in vitro experiments indicated that acute exposure of LCR muscle to (−)-epicatechin incubation was not sufficient to increase mitochondrial respiration. The results suggest that increases in skeletal muscle capillarity and mitochondrial biogenesis are associated with 30 days of (−)-epicatechin treatment and sustained for 15 days following cessation of treatment. Clinically, the use of this natural compound may have potential application in populations that experience muscle fatigue and are unable to perform endurance exercise.

scholarly journals EFFECT OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-ALPHA-AGONISTS ON DIABETES-INDUCED ACUTE KIDNEY INJURY: ROLE OF OXIDATIVE STRESS AND HYPERLIPIDEMIA

2019 ◽  
Vol 12 (1) ◽  
pp. 143
Author(s):  
Vishal Arvind Chakkarwar ◽  
Pravin Kawtikwar
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Single Dose ◽  
Lipid Profile ◽  
Density Lipoprotein ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

Objective: The present study investigated the possible effect of fenofibrate and gemfibrozil peroxisome proliferator-activated receptor-alpha agonist in diabetes-induced acute kidney injury (AKI) in rats.Methods: Rats were administered streptozotocin (STZ) (50 mg/kg, i.p., single dose) to induce experimental diabetes mellitus. The development of diabetic AKI was assessed biochemically and histologically. In addition, the diabetes-induced lipid profile and renal oxidative stress were assessed. The single dose of STZ produced diabetes, which induced renal oxidative stress, altered the lipid profile and subsequently produced kidney injuryAKI in 7 weeks by increasing serum creatinine, blood urea nitrogen (BUN), proteinuria, and glomerular damage. Treatment with fenofibrate and gemfibrozil (30 mg/kg p.o, 7 weeks) normalized the altered lipid profile by decreasing serum cholesterol, triglycerides, and increasing serum high-density lipoprotein in diabetic rats. Lisinopril (1 mg/kg, p.o., 7 weeks, reference compound) prevents lipid alteration and development of diabetic AKI.Result: Fenofibrate and gemfibrozil, besides hyperglycemia, significantly prevented the development of diabetic AKI by reducing (serum and tissue) oxidative stress, hyperlipidemia, serum BUN, creatinine, and urinary protein. Further, fenofibrate, but not gemfibrozil, considerably reduced renal structural and functional abnormalities in diabetic rats. The fenofibrate was more effective in attenuating the diabetes-induced AKI and renal oxidative stress as compared to treatment with and gemfibrozil.Conclusion: The fenofibrate and gemfibrozil treatment markedly prevented the diabetes-induced AKI. In comparison, the fenofibrate is found to be a superior approach to attenuate the diabetic AKI than gemfibrozil.

scholarly journals The Effect of Superoxide Dismutase on Inhibition of Acute Kidney Injury Induced by Sepsis Based on Kidney Tissue Histology and Murine Sepsis Score

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Jufitriani Ismy ◽  
Maimun Syukri ◽  
Dessy R. Emril ◽  
Nanan Sekarwana ◽  
Jufriady Ismy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Superoxide Dismutase ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Male Rats ◽  
Control Group ◽  
Control Group Design ◽  
Group I ◽  
Sepsis Score

Sepsis is one of the leading causes contributing to the incidence of acute kidney injury (AKI). Oxidative stress can be used as the main approach against sepsis-induced AKI. One of the primary antioxidants that plays a role in warding off oxidative stress is superoxide dismutase (SOD). This research aimed to observe the effect of antioxidant SOD in inhibiting sepsis in AKI based on kidney tissue histopathology. The research method was an experimental laboratory with a post-test-only control group design. Twenty-five adult male rats aged 12–16 weeks, weighing between 200 and 250 g, were randomly divided into five groups: Group I, as a positive control, where rats were injected with lipopolysaccharides (LPS); Group II, as a negative control; Group III, as treatment 1, where rats were injected with LPS and administered orally with SOD (Glisodin®) 250 IU daily; Group IV, as treatment 2, where rats were injected with LPS and administered orally with SOD (Glisodin®) 500 IU daily; and Group V, as treatment 2, where rats were injected with LPS and administered orally with SOD (Glisodin®) 1000 IU daily. Rats were administered with SOD (Glisodin®) by oral gavage with a flexible feeding tube for 16 weeks, given once daily in the morning, and then injected with LPS of 10 mg/kg body weight. Glisodin SOD had a significant effect on murine sepsis score (MSS). MSS influenced the tubular injury score linearly. We conclude that the optimal dose of SOD at 1000 IU for inhibiting sepsis-induced AKI incidence is compared to SOD at a dose of 250 and 500 IU. The antioxidant effect of SOD can prevent sepsis-induced AKI with oxidative stress events.

scholarly journals Nigella Sativa and Ginger Increase GLUT4 and PPARγ in Metabolic Syndrome‐Induced Rats

2021 ◽  
Vol 11 (1) ◽  
pp. 3261-3269
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Glucose Transporter ◽  
Nigella Sativa ◽  
Body Weight Gain ◽  
Male Rats ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Increased fructose intake has been linked to the epidemiology of insulin resistance, type 2 diabetes mellitus, renal damage, and metabolic syndrome (MS). As oxidative stress plays a pivotal role in the pathology of insulin resistance, the present study was conducted to investigate the effects of Nigella Sativa (NS) and ginger as potent antioxidants on fructose-induced MS in rats. Male rats were fed with a high‐fructose high-fat-fed diet for 8 weeks. By the end of the 8th week, rats were divided into four groups; one was left untreated (normal control) and MS control group was treated with saline. MS groups were given Nigella sativa (4 ml/kg) and ginger (500 mg/kg) daily for 4 weeks. Markers chosen for assessment included the effect on body weight gain, glucose, insulin, adiponectin levels, and lipid profile. Also, protein expressions were estimated by glucose transporter 4 (GLUT4) content and peroxisome proliferator‐activated receptor‐gamma (PPARγ). Nigella sativa and ginger ameliorated some manifestations of MS, including an increase in body weight, glucose, insulin level, and resistance. Besides, both drugs lowered insulin resistance, induced hyperlipidemia and increased adiponectin level. Drugs also increased GLUT4 and PPARγ protein expression compared with MS control group. Nigella sativa and ginger ameliorated parameters of MS via increased GLUT4 and PPARγ expression.

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