scholarly journals The Effects of Two Different Dietary Regimens During Exercise On Outcome of Experimental Acute Kidney Injury

2021 ◽  
Author(s):  
Nazanin Sabet ◽  
Zahra Soltani ◽  
Mohammad Khaksari ◽  
Alireza Raji- amirhasani
Keyword(s):  
Acute Kidney Injury ◽  
Transforming Growth Factor ◽  
Kidney Injury ◽  
Exercise Group ◽  
Urinary Albumin ◽  
Serum Urea ◽  
Kidney Weight ◽  
Excretory Function ◽  
Total Antioxidant ◽  
Tgf Β1

Abstract Introduction: Acute kidney injury (AKI) is a syndrome characterized by rapid loss of excretory function of kidney. One of the molecules considered in the treatment of renal failure is the silent information regulator (SIRT1). In this study, the effect of two different diets during exercise on AKI was investigated. Materials and Methods: A number of rats were randomly divided into four groups; control without exercise, control with exercise, exercise + calorie restriction (CR), and exercise + time restriction (TR). Each group was divided into two subgroups of without AKI and with AKI (six rats in each group). Endurance exercise and diets were implemented before AKI. Serum urea and creatinine, urinary albumin, kidney malondialdehyde (MDA), total antioxidant capacity (TAC), transforming growth factor (TGF-β1), and SIRT1 levels, glomerular filtration rate (GFR) and relative kidney weight were measured before and 48 h after AKI induction.Results: After induction of kidney injury, serum urea and creatinine, urinary albumin, kidney MDA and TGF-β1 levels and relative kidney weight increased in rats with both previous exercise and no previous exercise (p <0.001), while GFR, and kidney TAC and SIRT1 levels decreased (p <0.001). These changes after AKI were less in the group with previous exercise than in the group that had no exercise (p <0.001). The TR diet during exercise caused a less increase in serum urea (p <0.001) and creatinine (p <0.05), and urinary albumin (p <0.01) levels after injury compared to the just exercise group. Also, both CR and TR diets during exercise caused less change in MDA (p <0.01, p <0.05, respectively) and TAC (p <0.001, p <0.05, respectively) levels compared to just exercise group. Conclusion: The results showed that exercise alone had no effect on preventing function impairment of kidney, oxidative stress, inflammation and also SIRT1 alteration following AKI in athletes, although these indexes were less among those with exercise than those without exercise. However, when the CR and TR diets were implemented during exercise, strong renoprotective effects appeared, and the protective effect of TR diet was greater.

scholarly journals KIM-1 and GADDI-153 gene expression in paracetamol-induced acute kidney injury: effects of N-acetylcysteine, N-acetylmethionine, and N-acetylglucosamine

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Nahed A. Mohamed ◽  
Mohammed H. Hassan ◽  
Tahia H. Saleem ◽  
Sotohy A. Mohamed ◽  
Marwa El-Zeftawy ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Male Rats ◽  
Clinical Event ◽  
Serum Urea ◽  
Biochemical Alterations ◽  
Excretory Function ◽  
Genetic Mechanisms ◽  
Kidney Injury Molecule 1

Abstract Objectives Acute kidney injury (AKI) is a critical clinical event characterized by a reduction in the excretory function of the kidneys. N-acetylcysteine (NAC), N-acetylmethionine (NAM) and N-acetylglucosamine (NAG) are antioxidants with scanty known genetic mechanisms. We aimed to assess both kidney injury molecule-1 (KIM-1) and growth-arrested DNA damage-inducible gene-153 (GADD-153) genes expression in paracetamol (PA) induced AKI. Also, to recognize whether NAC, NAM and/or NAG have roles in altering the expression of these genes for ameliorating the AKI induced by PA. Methods The present preliminary study achieved the AKI model by oral administration of PA therapeutic dose for 15 days in experimental male rats. Serum urea, creatinine, and renal oxidative stress parameters were analyzed. Genetic expression of KIM-1 and GADD-153 were determined using real time-PCR. Results Significant elevations of serum urea, creatinine and nitric oxide in renal tissue after PA administration; however, total thiol content was reduced. In addition, both KIM-1 and GADD-153 were upregulated. These biochemical alterations were improved after using NAC and partially after NAM; however, NAG had little effect. Conclusions Up-regulation of both KIM-1 and GADD-153 occur in AKI induced by PA, which was significantly reversed by NAC.

scholarly journals N-acetyl-cysteine increases cellular dysfunction in progressive chronic kidney damage after acute kidney injury by dampening endogenous antioxidant responses

2018 ◽  
Vol 314 (5) ◽  
pp. F956-F968 ◽  
Author(s):  
David M. Small ◽  
Washington Y. Sanchez ◽  
Sandrine F. Roy ◽  
Christudas Morais ◽  
Heddwen L. Brooks ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Mitochondrial Dysfunction ◽  
Transforming Growth Factor ◽  
Multiphoton Microscopy ◽  
Kidney Injury ◽  
Peroxisome Proliferator ◽  
Fluorescence Lifetime Imaging ◽  
Antioxidant Responses ◽  
Acetyl Cysteine

Oxidative stress and mitochondrial dysfunction exacerbate acute kidney injury (AKI), but their role in any associated progress to chronic kidney disease (CKD) remains unclear. Antioxidant therapies often benefit AKI, but their benefits in CKD are controversial since clinical and preclinical investigations often conflict. Here we examined the influence of the antioxidant N-acetyl-cysteine (NAC) on oxidative stress and mitochondrial function during AKI (20-min bilateral renal ischemia plus reperfusion/IR) and progression to chronic kidney pathologies in mice. NAC (5% in diet) was given to mice 7 days prior and up to 21 days post-IR (21d-IR). NAC treatment resulted in the following: prevented proximal tubular epithelial cell apoptosis at early IR (40-min postischemia), yet enhanced interstitial cell proliferation at 21d-IR; increased transforming growth factor-β1 expression independent of IR time; and significantly dampened nuclear factor-like 2-initiated cytoprotective signaling at early IR. In the long term, NAC enhanced cellular metabolic impairment demonstrated by increased peroxisome proliferator activator-γ serine-112 phosphorylation at 21d-IR. Intravital multiphoton microscopy revealed increased endogenous fluorescence of nicotinamide adenine dinucleotide (NADH) in cortical tubular epithelial cells during ischemia, and at 21d-IR that was not attenuated with NAC. Fluorescence lifetime imaging microscopy demonstrated persistent metabolic impairment by increased free/bound NADH in the cortex at 21d-IR that was enhanced by NAC. Increased mitochondrial dysfunction in remnant tubular cells was demonstrated at 21d-IR by tetramethylrhodamine methyl ester fluorimetry. In summary, NAC enhanced progression to CKD following AKI not only by dampening endogenous cellular antioxidant responses at time of injury but also by enhancing persistent kidney mitochondrial and metabolic dysfunction.

Pathophysiology of Acute Kidney Injury

2017 ◽  
Author(s):  
Shalini Bumb ◽  
Andrew Malone ◽  
Matthew A. Sparks
Keyword(s):  
Acute Kidney Injury ◽  
Fluid Overload ◽  
Kidney Injury ◽  
Tissue Perfusion ◽  
Urinary Flow ◽  
Cellular Injury ◽  
Waste Products ◽  
Excretory Function ◽  
Tubular Necrosis ◽  
Vascular Compromise

Acute kidney injury (AKI) is defined as the abrupt loss of kidney excretory function with the accumulation of nitrogenous waste products and fluid overload. The etiologies of AKI are numerous and can largely be classified as prerenal, intrinsic, or postrenal. Complex pathways involving inflammatory mediators, vascular compromise, and direct cellular injury are triggered, and equally as complex pathways, including autophagy and fibrosis, are involved in the recovery. Prerenal azotemia is caused by a reduction in tissue perfusion with resulting AKI. Although acute tubular necrosis is the most common intrinsic etiology, other nephrotoxins and exposures can result in intrinsic injury as well. Postrenal AKI is due to obstruction of urinary flow. Herein, in further detail, the mechanisms, pathophysiology, and manifestations of these causes of AKI are discussed. Research into the mechanisms and development of markers and techniques to advance clinical practice is ongoing.

Acute kidney injury

2020 ◽  
pp. 4807-4829
Author(s):  
John D. Firth
Keyword(s):  
Acute Kidney Injury ◽  
Specific Treatment ◽  
Kidney Injury ◽  
Initial Assessment ◽  
Volume Depletion ◽  
Excretory Function ◽  
Tubular Necrosis ◽  
Life Threatening ◽  
Common Precipitant ◽  
General Aspects

Definition—for practical clinical purposes, acute kidney injury (AKI) is defined as a significant decline in renal excretory function occurring over hours or days, detected by either a fall in urinary output or a rise in the serum concentration of creatinine. Oliguria—defined (arbitrarily) as a urinary volume of less than 400 ml/day—is usually present, but not always. Clinical approach: diagnosis—all patients admitted to hospital with acute illness, but particularly older people and those with pre-existing chronic kidney disease, should be considered at risk of developing AKI. The most common precipitant is volume depletion. Serum creatinine and electrolytes should be measured on admission in all acutely ill patients, and repeated daily or on alternate days in those who remain so. Assessment—after treatment of life-threatening complications, the initial assessment of a patient who appears to have AKI must answer three questions: (1) is the kidney injury really acute? (2) Is urinary obstruction a possibility? And (3) is there a renal inflammatory cause? General aspects of management—the immediate management of a patient with renal impairment is directed towards three goals: (1) recognition and treatment of any life-threatening complications of AKI, (2) prompt diagnosis and treatment of hypovolaemia, and (3) specific treatment of the underlying condition—if this persists untreated then renal function will not improve. Specific causes of acute kidney injury—there are many possible causes of AKI, but in any given clinical context few of these are likely to require consideration. By far the most frequent are prerenal failure and acute tubular necrosis, which together account for 80 to 90% of cases of AKI seen by physicians.

scholarly journals TAK1 deficiency attenuates cisplatin-induced acute kidney injury

2020 ◽  
Vol 318 (1) ◽  
pp. F209-F215 ◽  
Author(s):  
Jun Zhou ◽  
Changlong An ◽  
Xiaogao Jin ◽  
Zhaoyong Hu ◽  
Robert L. Safirstein ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Proximal Tubule ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Kidney Injury ◽  
Transforming Growth Factor Β ◽  
Tubular Epithelial Cell ◽  
Tubular Damage ◽  
Wild Type ◽  
Deficient Mice

Cisplatin can cause acute kidney injury (AKI), but the molecular mechanisms are not well understood. The objective of the present study was to examine the role of transforming growth factor-β-activated kinase-1 (TAK1) in the pathogenesis of cisplatin-induced AKI. Wild-type mice and proximal tubule TAK1-deficient mice were treated with vehicle or cisplatin. Compared with wild-type control mice, proximal tubule TAK1-deficient mice had less severe kidney dysfunction, tubular damage, and apoptosis after cisplatin–induced AKI. Furthermore, conditional disruption of TAK1 in proximal tubular epithelial cells reduced caspase-3 activation, proinflammatory molecule expression, and JNK phosphorylation in the kidney in cisplatin-induced AKI. Taken together, cisplatin activates TAK1-JNK signaling pathway to promote tubular epithelial cell apoptosis and inflammation in cisplatin-induced AKI. Targeting TAK1 could be a novel therapeutic strategy against cisplatin-induced AKI.

scholarly journals All-Trans Retinoic Acid Attenuates Fibrotic Processes by Downregulating TGF-β1/Smad3 in Early Diabetic Nephropathy

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 525 ◽  
Author(s):  
Edith Sierra-Mondragon ◽  
Rafael Rodríguez-Muñoz ◽  
Carmen Namorado-Tonix ◽  
Eduardo Molina-Jijon ◽  
Daniel Romero-Trejo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Retinoic Acid ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Smooth Muscle Actin ◽  
Kidney Injury ◽  
Alpha Smooth Muscle Actin ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Tgf Β1

Diabetic nephropathy (DN) involves damage associated to hyperglycemia and oxidative stress. Renal fibrosis is a major pathologic feature of DN. The aim of this study was to evaluate anti-fibrogenic and renoprotective effects of all-trans retinoic acid (ATRA) in isolated glomeruli and proximal tubules of diabetic rats. Diabetes was induced by single injection of streptozotocin (STZ, 60 mg/Kg). ATRA (1 mg/Kg) was administered daily by gavage, from days 3–21 after STZ injection. ATRA attenuated kidney injury through the reduction of proteinuria, renal hypertrophy, increase in natriuresis, as well as early markers of damage such as β2-microglobulin, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL). The following parameters increased: macrophage infiltration, localization of alpha-smooth muscle actin (αSMA)-positive cells in renal tissue, and pro-fibrotic proteins such as transforming growth factor-β (TGF-β1), laminin beta 1 (LAM-β1), and collagens IV and I. Remarkably, ATRA treatment ameliorated these alterations and attenuated expression and nuclear translocation of Smad3, with increment of glomerular and tubular Smad7. The diabetic condition decreased expression of retinoic acid receptor alpha (RAR-α) through phosphorylation in serine residues mediated by the activation of c-Jun N-terminal kinase (JNK). ATRA administration restored the expression of RAR-α and inhibited direct interactions of JNK/RAR-α. ATRA prevented fibrogenesis through down-regulation of TGF-β1/Smad3 signaling.

scholarly journals Metabolic Syndrome (MetS) and Nonalcoholic Steatohepatitis (NASH): Study of biochemical markers Free Fatty Acid (FFA), Total Antioxidant Status (TAOS), Adiponectin, Transforming Growth Factor (TGF-beta1), in occurence of NASH

2009 ◽  
Vol 1 (1) ◽  
pp. 40
Author(s):  
Agus Sulaeman ◽  
A Rifai Amiruddin ◽  
Gatot Susilo Lawrence
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Growth Factor ◽  
Free Fatty Acid ◽  
Fatty Liver ◽  
Antioxidant Status ◽  
Transforming Growth Factor ◽  
Total Antioxidant Status ◽  
Total Antioxidant ◽  
Tgf Β1

BACKGROUND: The prevalence of metabolic syndrome (MetS) in USA and Makassar are 22% and 23.7%. The prevalence of Non Alcoholic Steatosis Hepatosis (NASH) in MetS has not been reported. Study in Non-alcoholic Fatty Liver Disease (NAFLD) is 25–90 % in obesity patients. In NASH, there is accumulation of lipid in hepatocyte (raised free fatty acid level), raised stress oxidative (decreased total antioxidant status), raised of inflammation process (decreased adiponectin) and hepatic fibrotic process (raised TGF β1). The aim of this study is to investigate the correlation of free fatty acid, total antioxidant status, adiponectin and TGF-β1 with the occurrence of NASH.METHODS: This was a case control study in man aged ≥30 years old. Metabolic syndrome (MetS) was defined by IDF categories. NASH was defined as fatty liver plus raised type IV collagen level ≥140 ng/ml and Alanine Transferase (ALT) level 1.5x upper normal limit.RESULT: The samples consisted of 8 MetS subjects, 11 MetS subjects with fatty liver and 2 MetS subjects with suspect NASH. Low level of adiponectin and high level free fatty acid led to progression from Fatty Liver (FL) to NASH. Level of total antioxidant and Level of TGF-β1 were relatively steady in NASH.CONCLUSION: The level of Free Fatty acid in subjects with MetS-FL was higher than in subjects with MetS, but was lower than in subjects with MetS-NASH. No difference in total antioxidants status level was observed among all groups. Level of adiponectin decreased in subjects with MetS-FL and MetS-NASH compared with subjects with MetS only. The level of TGF-β1 increased in subjects with MetS-FL more than in subjects with MetS only, and was steady low in subjects with MetS-NASH.KEYWORDS: metabolic syndrome, NASH, free fatty acid, total antioxidant status, adiponectin, transforming growth factor β1

scholarly journals Melatonin Alleviates Contrast-Induced Acute Kidney Injury by Activation of Sirt3

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Chunmei Zhang ◽  
Mengying Suo ◽  
Lingxin Liu ◽  
Yan Qi ◽  
Chen Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Transforming Growth Factor ◽  
Kidney Injury ◽  
Transforming Growth Factor Β ◽  
Activity Levels ◽  
Protective Effects ◽  
Melatonin Treatment

Oxidative stress and apoptosis play a vital role in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). The purpose of our study was to investigate the protective effects and mechanisms of melatonin against CI-AKI in a CI-AKI mouse model and NRK-52E cells. We established the CI-AKI model in mice, and the animals were pretreated with melatonin (20 mg/kg). Our results demonstrated that melatonin treatment exerted a renoprotective effect by decreasing the level of serum creatinine (SCr) and blood urea nitrogen (BUN), lessening the histological changes of renal tubular injuries, and reducing the expression of neutrophil gelatinase-associated lipid (NGAL), a marker of kidney injury. We also found that pretreatment with melatonin remarkably increased the expression of Sirt3 and decreased the ac-SOD2 K68 level. Consequently, melatonin treatment significantly decreased the oxidative stress by reducing the Nox4, ROS, and malondialdehyde (MDA) content and by increasing the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity levels. The antiapoptotic effect of melatonin on CI-AKI was revealed by decreasing the ratio of Bax/Bcl2 and the cleaved caspase3 level and by reducing the number of apoptosis-positive tubular cells. In addition, melatonin treatment remarkably reduced the inflammatory cytokines of interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and transforming growth factor β (TGFβ) in vivo and in vitro. Sirt3 deletion and specific Sirt3 siRNA abolished the above renoprotective effects of melatonin in mice with iohexol-induced acute kidney injury and in NRK-52E cells. Thus, our results demonstrated that melatonin exhibited the renoprotective effects of antioxidative stress, antiapoptosis, and anti-inflammation by the activation of Sirt3 in the CI-AKI model in vivo and in vitro. Melatonin may be a potential drug to ameliorate CI-AKI in clinical practice.

scholarly journals Lovastatin Inhibits Transforming Growth Factor-β1 Expression in Diabetic Rat Glomeruli and Cultured Rat Mesangial Cells

2000 ◽  
Vol 11 (1) ◽  
pp. 80-87
Author(s):  
SUNG IL KIM ◽  
DONG CHEOL HAN ◽  
HI BAHL LEE
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Diabetic Rats ◽  
Kidney Weight ◽  
Urine Albumin Excretion ◽  
Urine Albumin ◽  
Ecm Proteins ◽  
Tgf Β1

Abstract. Diabetic nephropathy is a leading cause of end-stage renal disease and is characterized by excessive deposition of extracellular matrix (ECM) proteins in the glomeruli. Transforming growth factor-β (TGF-β) is the major mediator of excessive accumulation of ECM proteins in diabetic nephropathy through upregulation of genes encoding ECM proteins as well as downregulation of genes for ECM-degrading enzymes. It has been shown that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, delays the onset and progression of different models of experimental nephropathy. To evaluate the effect of lovastatin on the development and progression of diabetic nephropathy, streptozotocin-induced diabetic rats were studied for 12 mo. In untreated diabetic rats, there were significant increases in blood glucose, urine albumin excretion, kidney weight, glomerular volume, and TGF-β1 mRNA expression in the glomeruli compared with normal control rats treated with citrate buffer only. Treatment with lovastatin in diabetic rats significantly suppressed the increase in urine albumin excretion, kidney weight, glomerular volume, and TGF-β1 mRNA expression despite high blood glucose levels. To elucidate the mechanisms of the renal effects of lovastatin, rat mesangial cells were cultured under control (5.5 mM) or high (30 mM) glucose with lovastatin alone, mevalonate alone, or with both. Under high glucose, TGF-β1 and fibronectin mRNA and proteins were upregulated. These high glucose-induced changes were suppressed by lovastatin (10 μM) and nearly completely restored by mevalonate (100 μM). These results suggest that lovastatin has a direct cellular effect independent of a cholesterol-lowering effect and delays the onset and progression of diabetic nephropathy, at least in part, through suppression of glomerular expression of TGF-β1.

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