scholarly journals Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Benjamin P. Larkin ◽  
Long T. Nguyen ◽  
Miao Hou ◽  
Sarah J. Glastras ◽  
Hui Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Dna Methylation ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Low Dose ◽  
Maternal Obesity ◽  
Global Dna Methylation ◽  
Dietary Obesity ◽  
And Oxidative Stress

BackgroundMaternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation. We used mouse models of maternal obesity and offspring obesity to determine whether administration of low-dose hydralazine during gestation can prevent fetal programming of CKD in offspring.MethodsFemale C57BL/6 mice received high fat diet (HFD) or chow prior to mating, during gestation and lactation. During gestation, dams received subcutaneous hydralazine (5 mg/kg) or saline thrice-weekly. Male offspring weaned to HFD or chow, which continued until endpoint at 32 weeks. Biometric and metabolic parameters, renal global DNA methylation, renal functional and structural changes, and renal markers of fibrosis, inflammation and oxidative stress were assessed at endpoint.ResultsOffspring exposed to maternal obesity or diet-induced obesity had significantly increased renal global DNA methylation, together with other adverse renal effects including albuminuria, glomerulosclerosis, renal fibrosis, and oxidative stress. Offspring exposed to gestational hydralazine had significantly reduced renal global DNA methylation. In obese offspring of obese mothers, gestational hydralazine significantly decreased albuminuria, glomerulosclerosis, and serum creatinine. Obese offspring of hydralazine-treated lean mothers displayed reduced markers of renal fibrosis and oxidative stress.ConclusionGestational hydralazine decreased renal global DNA methylation and exerted renoprotective effects in offspring. This supports a potential therapeutic effect of hydralazine in preventing maternal obesity or dietary obesity-related CKD, through an epigenetic mechanism.

scholarly journals Low-dose hydralazine during gestation reduces renal fibrosis in rodent offspring exposed to maternal high fat diet

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248854
Author(s):  
Benjamin P. Larkin ◽  
Sonia Saad ◽  
Sarah J. Glastras ◽  
Long T. Nguyen ◽  
Miao Hou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Methylation ◽  
Fetal Programming ◽  
High Fat Diet ◽  
Renal Fibrosis ◽  
Low Dose ◽  
Maternal Obesity ◽  
Metabolic Parameters ◽  
Global Dna Methylation ◽  
High Fat

Background Maternal high fat diet (HFD) promotes chronic kidney disease (CKD) in offspring. This is in accordance with the theory of fetal programming, which suggests adverse conditions occurring in utero predispose offspring to chronic conditions later in life. DNA methylation has been proposed as a key mechanism by which fetal programming occurs and is implicated in CKD progression. DNA demethylating drugs may interrupt the fetal programming of CKD by maternal obesity. Hydralazine, an antihypertensive agent, demethylates DNA at low doses which do not reduce blood pressure. We used a mouse model of maternal obesity to determine whether gestational administration of low-dose hydralazine to mothers can prevent CKD in offspring. Methods C57BL/6 dams received HFD or chow from 6 weeks prior to mating and were administered subcutaneous hydralazine (5mg/kg) or saline thrice weekly during gestation. Male offspring were weaned to chow and were sacrificed at either postnatal week 9 or week 32. Biometric and metabolic parameters, renal global DNA methylation, renal structural and functional changes and markers of fibrosis, oxidative stress and inflammation were measured in offspring at weeks 9 and 32. Results In week 9 offspring, maternal HFD consumption did not significantly alter anthropometric or metabolic parameters, or renal global DNA methylation. Week 32 offspring had increased renal global DNA methylation, together with albuminuria, glomerulosclerosis, renal fibrosis and oxidative stress. Administration of low-dose hydralazine to obese mothers during gestation reduced renal global DNA methylation and renal fibrotic markers in week 32 offspring. Conclusion Gestational hydralazine reduced renal global DNA methylation in offspring of obese mothers and attenuated maternal obesity-induced renal fibrosis. These data support the use of low-dose hydralazine as a demethylating agent to prevent CKD arising in offspring due to maternal HFD consumption.

scholarly journals Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 472
Author(s):  
Elisabetta Margiotta ◽  
Lara Caldiroli ◽  
Maria Luisa Callegari ◽  
Francesco Miragoli ◽  
Francesca Zanoni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Interleukin 10 ◽  
Uremic Toxins ◽  
Interleukin 12 ◽  
European Working ◽  
And Oxidative Stress

Background: Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. Methods: We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m2, not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Results: Sarcopenic patients had a greater abundance of the Micrococcaceae and Verrucomicrobiaceae families and of Megasphaera, Rothia, Veillonella, Akkermansia and Coprobacillus genera. They had a lower abundance of the Gemellaceae and Veillonellaceae families and of Acidaminococcus and Gemella genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. Conclusions: In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients.

scholarly journals Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0159411 ◽  
Author(s):  
Keith G. Avin ◽  
Neal X. Chen ◽  
Jason M. Organ ◽  
Chad Zarse ◽  
Kalisha O’Neill ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
And Oxidative Stress

scholarly journals Alteration and association between serum ACE2/ angiotensin(1-7)/Mas axis and oxidative stress in chronic kidney disease

Medicine ◽  
2020 ◽  
Vol 99 (31) ◽  
pp. e21492 ◽  
Author(s):  
Chengqian Shi ◽  
Keda Lu ◽  
Hong Xia ◽  
Peipei Zhang ◽  
Bingbing Zhang
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
And Oxidative Stress

Misdistribution of iron and oxidative stress in chronic kidney disease

2019 ◽  
Vol 133 ◽  
pp. 248-253 ◽  
Author(s):  
Takeshi Nakanishi ◽  
Takahiro Kuragano ◽  
Masayoshi Nanami ◽  
Yasuyuki Nagasawa ◽  
Yukiko Hasuike
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
And Oxidative Stress

scholarly journals Dietary Antioxidant Supplements and Uric Acid in Chronic Kidney Disease: A Review

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1911 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Evangelia Dounousi ◽  
Theodoros Eleftheriadis ◽  
Vassilios Liakopoulos
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Serum Levels ◽  
Maintenance Hemodialysis ◽  
Antioxidant Supplements ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Oxidative Stress

Increased serum levels of uric acid have been associated with the onset and development of chronic kidney disease (CKD), cardiovascular disease, and mortality, through several molecular pathogenetic mechanisms, such as inflammation and oxidative stress. Oxidative stress is present even in the early stages of CKD, progresses parallelly with the deterioration of kidney function, and is even more exacerbated in end-stage renal disease patients undergoing maintenance hemodialysis. Although acting in the plasma as an antioxidant, once uric acid enters the intracellular environment; it behaves as a powerful pro-oxidant. Exogenous intake of antioxidants has been repeatedly shown to prevent inflammation, atherosclerosis and oxidative stress in CKD patients. Moreover, certain antioxidants have been proposed to exert uric acid-lowering properties. This review aims to present the available data regarding the effects of antioxidant supplements on both oxidative stress and uric acid serum levels, in a population particularly susceptible to oxidative damage such as CKD patients.

scholarly journals Acute effects of intradialytic aerobic exercise on solute removal, blood gases and oxidative stress in patients with chronic kidney disease

2017 ◽  
Vol 39 (2) ◽  
Author(s):  
Joseane Böhm ◽  
Mariane Borba Monteiro ◽  
Francini Porcher Andrade ◽  
Francisco Veríssimo Veronese ◽  
Fernando Saldanha Thomé
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aerobic Exercise ◽  
Blood Gases ◽  
Acute Effects ◽  
And Oxidative Stress
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