scholarly journals Resveratrol Butyrate Ester Protects Adenine-Treated Rats against Hypertension and Kidney Disease by Regulating the Gut–Kidney Axis

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 83
Author(s):  
Chien-Ning Hsu ◽  
Chih-Yao Hou ◽  
Chi-I Chang ◽  
You-Lin Tain
Keyword(s):  
Kidney Disease ◽  
Gut Microbiota ◽  
Signaling Pathway ◽  
Kidney Damage ◽  
Receptor Expression ◽  
High Dose ◽  
Sprague Dawley ◽  
Renal Hypertrophy ◽  
Aryl Hydrocarbon ◽  
Underlying Mechanisms

Despite recent advances in pharma-nutritional management, chronic kidney disease (CKD) remains an increasingly prevalent disorder. Resveratrol, a pleiotropic phytochemical, has been found to reduce the risk for several chronic diseases. Considering the low bioavailability of resveratrol, we recently synthesized resveratrol butyrate ester (RBE) via the esterification of resveratrol with butyrate. The aim of this study was to examine the effectiveness of RBE as regards protection from hypertension and kidney damage and explore the underlying mechanisms using a young rat adenine-induced CKD model. Three-week-old male Sprague Dawley rats received regular or 0.5% adenine chow for three weeks. Three groups of adenine-fed CKD rats (N = 8/group) received resveratrol (50 mg/L), or a low dose (25 mg/L) or high dose (50 mg/L) of RBE in drinking water from week 6 to week 12. As compared with the controls, adenine-treated rats had markedly increased creatinine levels and blood pressure, which was associated with renal hypertrophy and decreased creatinine clearance. Treatment with resveratrol or a low or high dose of RBE, similarly protected adenine-fed rats against hypertension and kidney damage. CKD-induced hypertension is associated with an altered gut microbiota profile, dysregulated renal short chain fatty acid (SCFA) receptor expression, activation of the aryl hydrocarbon receptor (AhR) signaling pathway, and reduced nitric oxide bioavailability. We found gut microbiota compositions were shaped differentially by resveratrol and RBE treatment in adenine-treated CKD rats. The beneficial effect of high-dose RBE was associated with reduced renal expression of SCFA G protein-coupled receptor 41 (GPR41) and olfactory receptor 78 (Olfr78), antagonizing the AhR signaling pathway, and increased abundance of beneficial bacteria such as genera Akkermansia, Blautia, and Enterococcus. Our study provided the first evidence documenting RBE as a novel phytochemical supplement targeting the gut–kidney axis to protect against adenine-induced kidney damage and hypertension.

scholarly journals Maternal Tryptophan Supplementation Protects Adult Rat Offspring against Hypertension Programmed by Maternal Chronic Kidney Disease: Implication of Tryptophan-Metabolizing Microbiome and Aryl Hydrocarbon Receptor

2020 ◽  
Vol 21 (12) ◽  
pp. 4552 ◽  
Author(s):  
Chien-Ning Hsu ◽  
I-Chun Lin ◽  
Hong-Ren Yu ◽  
Li-Tung Huang ◽  
Mao-Meng Tiao ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Aryl Hydrocarbon Receptor ◽  
Female Rats ◽  
Adult Offspring ◽  
Sprague Dawley ◽  
Aryl Hydrocarbon ◽  
Induced Hypertension ◽  
In Pregnancy

Hypertension and chronic kidney disease (CKD) can originate during early-life. Tryptophan metabolites generated by different pathways have both detrimental and beneficial effects. In CKD, uremic toxins from the tryptophan-generating metabolites are endogenous ligands of the aryl hydrocarbon receptor (AHR). The interplay between AHR, nitric oxide (NO), the renin–angiotensin system (RAS), and gut microbiota is involved in the development of hypertension. We examined whether tryptophan supplementation in pregnancy can prevent hypertension and kidney disease programmed by maternal CKD in adult offspring via the aforementioned mechanisms. Sprague–Dawley (SD) female rats received regular chow or chow supplemented with 0.5% adenine for 3 weeks to induce CKD before pregnancy. Pregnant controls or CKD rats received vehicle or tryptophan 200 mg/kg per day via oral gavage during pregnancy. Male offspring were divided into four groups (n = 8/group): control, CKD, tryptophan supplementation (Trp), and CKD plus tryptophan supplementation (CKDTrp). All rats were sacrificed at the age of 12 weeks. We found maternal CKD induced hypertension in adult offspring, which tryptophan supplementation prevented. Maternal CKD-induced hypertension is related to impaired NO bioavailability and non-classical RAS axis. Maternal CKD and tryptophan supplementation differentially shaped distinct gut microbiota profile in adult offspring. The protective effect of tryptophan supplementation against maternal CKD-induced programmed hypertension is relevant to alterations to several tryptophan-metabolizing microbes and AHR signaling pathway. Our findings support interplay among tryptophan-metabolizing microbiome, AHR, NO, and the RAS in hypertension of developmental origins. Furthermore, tryptophan supplementation in pregnancy could be a potential approach to prevent hypertension programmed by maternal CKD.

scholarly journals Shengjing Capsule Improves Spermatogenesis through Upregulating Integrin α6/β1 in the NOA Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jiamin Wang ◽  
Shankun Zhao ◽  
Lianmin Luo ◽  
Yangzhou Liu ◽  
Ermao Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sperm Quality ◽  
Sperm Count ◽  
Spermatogonial Stem Cells ◽  
Normal Group ◽  
Seminiferous Tubules ◽  
High Dose ◽  
Sprague Dawley ◽  
Underlying Mechanisms ◽  
Almost All

Objective. To evaluate the therapeutic effect of Shengjing capsules on nonobstructive azoospermia (NOA) in the rat model. Methods. Twenty-five male Sprague–Dawley rats were randomly divided into five groups as follows (n=5 per group): normal group, NOA group, and three Shengjing capsule treatment groups (low-dose, medium-dose, and high-dose groups, respectively). HE staining and semen smear were performed to assess sperm quality. The expression levels of PI3K/AKT and integrin α6/β1 were measured by qRT-PCR and western blot analyses. Results. In the NOA group, almost all of the seminiferous tubules were vacuolated with a thin layer of basal compartment containing some spermatogonial stem cells. The counts of sperms in the NOA group were strongly lower than those of the normal group (P=0.0001). The expression of PI3K/AKT and integrin α6/β1 was scarcely expressed in the NOA group. All indexes mentioned above were significantly different from those of the medium- and high-dose groups (P=0.001, all). The sperm count of rats treated with Shengjing capsules was significantly higher than that of the NOA group (P=0.0001). The rats of Shengjing capsule groups had more layers of spermatogonial stem cells and spermatocytes, and some had intracavitary sperms. Conclusions. Shengjing capsules may be a promising therapeutic medicine for NOA. The underlying mechanisms might involve activating SSCs by upregulating the integrin α6/β1 expression via the PI3K/AKT pathway.

scholarly journals Intermittent hypoxia exacerbates increased blood pressure in rats with chronic kidney disease

2018 ◽  
Vol 315 (4) ◽  
pp. F927-F941 ◽  
Author(s):  
Jennifer L. Riggs ◽  
Carolyn E. Pace ◽  
Heather H. Ward ◽  
Laura V. Gonzalez Bosc ◽  
Lynnette Rios ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intermittent Hypoxia ◽  
Interstitial Fibrosis ◽  
Control Diet ◽  
Kidney Injury ◽  
Kidney Damage ◽  
Plasma Creatinine ◽  
Sprague Dawley

Kidney injury and sleep apnea (SA) are independent risk factors for hypertension. Exposing rats to intermittent hypoxia (IH) to simulate SA increases blood pressure whereas adenine feeding causes persistent kidney damage to model chronic kidney disease (CKD). We hypothesized that exposing CKD rats to IH would exacerbate the development of hypertension and renal failure. Male Sprague-Dawley rats were fed a 0.2% adenine diet or control diet (Control) until blood urea nitrogen was >120 mg/dl in adenine-fed rats (14 ± 4 days, mean ± SE). After 2 wk of recovery on normal chow, rats were exposed to IH (20 exposures/h of 5% O2-5% CO2 7 h/day) or control conditions (Air) for 6 wk. Mean arterial pressure (MAP) was monitored with telemeters, and plasma and urine samples were collected weekly to calculate creatinine clearance as an index of glomerular filtration rate (GFR). Prior to IH, adenine-fed rats had higher blood pressure than rats on control diet. IH treatment increased MAP in both groups, and after 6 wk, MAP levels in the CKD/IH rats were greater than those in the CKD/Air and Control/IH rats. MAP levels in the Control/Air rats were lower than those in the other three groups. Kidney histology revealed crystalline deposits, tubule dilation, and interstitial fibrosis in both CKD groups. IH caused no additional kidney damage. Plasma creatinine was similarly increased in both CKD groups throughout whereas IH alone increased plasma creatinine. IH increases blood pressure further in CKD rats without augmenting declines in GFR but appears to impair GFR in healthy rats. We speculate that treating SA might decrease hypertension development in CKD patients and protect renal function in SA patients.

scholarly journals Molecular Basis of Kidney Defects in COVID-19 Patients

2020 ◽  
Author(s):  
Smartya Pulai ◽  
Madhurima Basu ◽  
Chinmay Saha ◽  
Nitai P. Bhattacharyya ◽  
Arpita Ray Chaudhury ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Signaling Pathway ◽  
Bacterial Infections ◽  
Enrichment Analysis ◽  
Kidney Damage ◽  
Gene Expressions ◽  
Infected Cells ◽  
Syncytial Virus

Background: Kidney damage is considered to be one of the risk factors for severity and mortality among COVID-19 patients. However, molecular nature of such observations remains unknown. Hypothesis: Altered gene expressions due to infection and in chronic kidney disease could explain severity in COVID-19 with kidney defects. Methods: We collected gene expression data from publicly available resources Gene Expression Omnibus CKD, Enrichr for deregulated genes in SARS-CoV infected cells in vitro, DisGeNET and others and carried out enrichment analysis using Enrichr. Result: Number of common genes altered in chronic kidney disease (CKD) and SARS-CoV infected cells was 2834. Enrichment analysis revealed that biological processes related viral life cycle and growth, cytokines, immunity, interferon, inflammation, apoptosis, autophagy, oxidative stress and others were significantly enriched with common deregulated genes. Similarly, significantly enriched pathways related to viral and bacterial infections, immunity and inflammation, cell cycle, ubiquitin mediated proteolysis, signaling pathways like Relaxin signaling pathway, mTOR signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway were enriched with the common deregulated genes. These processes and pathways are known to be related to kidney damage. DisGeNET terms enriched include and related to Dengue fever, chronic Hepatitis, measles, retroviridae infections, respiratory syncytial virus Infections and many others. Kidney dysfunction related terms ischemia of kidney, renal fibrosis and diabetic nephropathy. Conclusion: Common deregulated genes in SARS-CoV infected cells and chronic kidney disease, as well as their enrichment with molecular processes and pathways relevant for viral pathogenesis and renal dysfunctions, could explain the severity of COVID-19 with kidney disease. This observation not only provides molecular relation of severity in COVID-19 with renal dysfunctions but might also help in the management and treatment targets for these cases.

scholarly journals Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes

2006 ◽  
Vol 188 (2) ◽  
pp. 263-270 ◽  
Author(s):  
E Kim ◽  
S Sohn ◽  
M Lee ◽  
J Jung ◽  
R D Kineman ◽  
...  
Keyword(s):  
Receptor Expression ◽  
High Dose ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Β Cells ◽  
Igf I ◽  
Chemical Destruction ◽  
Catabolic State ◽  
Rats And Mice ◽  
The Impact

The impact of streptozotocin (STZ)-induced, insulinopenic diabetes on the GH axis of rats and mice differs from study to study, where this variation may be related to the induction scheme, severity of the diabetes and/or the genetic background of the animal model used. In order to begin differentiate between these possibilities, we compared the effects of two different STZ induction schemes on the GH axis of male Sprague–Dawley rats: (1) a single high-dose injection of STZ (HI STZ, 80 mg/kg, i.p.), which results in rapid chemical destruction of the pancreatic β-cells, and (2) multiple low-dose injections of STZ (LO STZ, 20 mg/kg for 5 consecutive days, i.p.), which results in a gradual, autoimmune destruction of β-cells. STZ-treated animals were killed after 3 weeks of hyperglycemia (>400 mg/dl), and in both paradigms circulating insulin levels were reduced to <40% of vehicle-treated controls. HI STZ-treated rats lost weight, while body weights of LO STZ-treated animals gradually increased over time, similar to vehicle-treated controls. As previously reported, HI STZ resulted in a decrease in circulating GH and IGF-I levels which was associated with a rise in hypothalamic neuropeptide Y (NPY) mRNA (355% of vehicle-treated controls) and a fall in GH-releasing hormone (GHRH) mRNA (45% of vehicle-treated controls) levels. Changes in hypothalamic neuropeptide expression were reflected by an increase in immunoreactive NPY within the arcuate and paraventricular nuclei and a decrease in GHRH immunoreactivity in the arcuate nucleus, as assessed by immunohistochemistry. Consistent with the decline in circulating GH and hypothalamic GHRH, pituitary GH mRNA levels of HI STZ-treated rats were 58% of controls. However, pituitary receptor mRNA levels for GHRH and ghrelin increased and those for somatostatin (sst2, sst3 and sst5) decreased following HI STZ treatment. The impact of LO STZ treatment on the GH axis differed from that observed following HI STZ treatment, despite comparable changes in circulating glucose and insulin. Specifically, LO STZ treatment did suppress circulating IGF-I levels to the same extent as HI STZ treatment; however, the impact on hypothalamic NPY mRNA levels was less dramatic (158% of vehicle-treated controls) where NPY immunoreactivity was increased only within the paraventricular nucleus. Also, there were no changes in circulating GH, hypothalamic GHRH or pituitary receptor expression following LO STZ treatment, with the exception that pituitary sst3 mRNA levels were suppressed compared with vehicle-treated controls. Taken together these results clearly demonstrate that insulinopenia, hyperglycemia and reduced circulating IGF-I levels are not the primary mediators of hypothalamic and pituitary changes in the GH axis of rats following HI STZ treatment. Changes in the GH axis of HI STZ-treated rats were accompanied by weight loss, and these changes are strikingly similar to those observed in the fasted rat, which suggests that factors associated with the catabolic state are critical in modifying the GH axis following STZ-induced diabetes.

scholarly journals Qingshen Buyang Formula Attenuates Renal Fibrosis in 5/6 Nephrectomized Rats via Inhibiting EMT and Wnt/β-Catenin Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Xueqin Zhang ◽  
Jing Fang ◽  
Zhiqiang Chen ◽  
Bingwu Zhao ◽  
Su Wu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Intragastric Administration ◽  
Sham Operation ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Sham Operation Group ◽  
Group 5 ◽  
Underlying Mechanisms

As renal fibrosis significantly contributes to various kinds of chronic kidney diseases, this study aimed to investigate the renal protective effects of Qingshen Buyang Formula against renal fibrosis on 5/6 nephrectomized rats, and its underlying mechanisms were explored. A total of 24 male Sprague-Dawley rats were randomly divided into sham operation group (Sham group), 5/6 nephrectomy group (5/6Nx group), and Qingshen Buyang Formula treatment group (QBF group). The intervention was intragastric administration for 12 weeks. In the end, the blood samples were collected to test renal functional parameters, urine proteins were measured, and the left kidneys were removed for histological studies, as well as mRNA and protein expression analysis. The results showed that Qingshen Buyang Formula significantly decreased BUN, Scr, and proteinuria in 5/6Nx rats. Meanwhile, it ameliorated the kidney injury and fibrosis, exemplified by the depressed expression of collagen I and fibronectin (FN), which are the main components of ECM. Furthermore, the process of EMT inhibited the Wnt/β-catenin signaling pathway related genes, such as Wnt4, TCF4, β-catenin, and p-GSK3β. Collectively, the Qingshen Buyang Formula can improve renal function and attenuate renal fibrosis, and its underlying mechanisms may be related with inhibiting EMT and Wnt/β-catenin signaling pathway.

scholarly journals Antidepressant-Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF-ERK-CREB Signaling Pathway in the Hippocampus and Frontal Cortex

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Lijing Yan ◽  
Xia Xu ◽  
Zhenyu He ◽  
Sheng Wang ◽  
Linlin Zhao ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Frontal Cortex ◽  
Signaling Pathway ◽  
Low Dose ◽  
Antidepressant Effect ◽  
Control Group ◽  
High Dose ◽  
Mild Stress ◽  
Sprague Dawley ◽  
Bdnf Mrna

Background. Fluoxetine (FLU) is the first-line and widely used medication for depression; however, FLU treatment is almost ineffective in 30%-40% of patients with depression. In addition, there are some problems in FLU treatment, such as delayed efficacy, large side effects, and poor tolerance. Chaihu Shugan San (CSS) is a classic and effective antidepressant Chinese herbal medicine that has been used in China for thousands of years. CSS or coadministration of CSS and FLU has become one of the most recommended methods in the treatment of depression in China. However, the specific pathways of CSS and coadministration of CSS and FLU for antidepressant are still unclear. Objective. This study was designed to evaluate the antidepressant effects of CSS and coadministration of CSS and FLU. Methods. The chronic unpredictable mild stress (CUMS) rat model was used to simulate depression. 120 healthy adult male Sprague-Dawley (SD) rats were randomly divided into seven groups: the control group, CUMS group, low-dose CSS group, high-dose CSS group, FLU group, coadministration of low-dose CSS and FLU group, and coadministration of high-dose CSS and FLU group. The rats in different groups were given different interventions. Then, the depression-like behavior and cognitive function were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and Y-maze test. What is more, the antidepressant mechanism of CSS and coadministration of CSS and FLU were studied through BDNF mRNA, ERK mRNA, CREB mRNA, BDNF, p-ERK/ERK, and p-CREB/CREB levels in the hippocampus and frontal cortex by Western blot and RT-PCR. Results. Compared with the CUMS group, CSS and coadministration of CSS and FLU could alleviate the depressive symptoms and improve cognitive function in CUMS rats (p<0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p<0.05). Besides, the high-dose CSS combined with the fluoxetine group was significantly better than the fluoxetine group and CSS group (p<0.05). Discussion and Conclusion. Finally, we found that both CSS and coadministration of CSS and FLU play an antidepressant role, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway in the hippocampus and frontal cortex. Among them, the coadministration of CSS and FLU can enhance the antidepressant effect of CSS or FLU alone, and the underlying mechanism needs further investigation.

scholarly journals Melatonin Prevents Chronic Kidney Disease-Induced Hypertension in Young Rat Treated with Adenine: Implications of Gut Microbiota-Derived Metabolites

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1211
Author(s):  
Chien-Ning Hsu ◽  
Hung-Wei Yang ◽  
Chih-Yao Hou ◽  
Guo-Ping Chang-Chien ◽  
Sufan Lin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Kidney Injury ◽  
Male Rats ◽  
Uremic Toxin ◽  
Protective Effects ◽  
Renal Hypertrophy ◽  
Α Diversity ◽  
Young Rat

Melatonin, a signaling hormone with pleiotropic biofunctions, has shown health benefits. Trimethylamine-N-oxide (TMAO) and asymmetric dimethylarginine (ADMA) are uremic toxins involved in the development of hypertension. TMAO originates from trimethylamine (TMA), a gut microbial product. ADMA is an endogenous nitric oxide (NO) synthase inhibitor. We examined whether melatonin therapy could prevent hypertension and kidney disease by mediating gut microbiota-derived metabolites and the NO pathway using an adenine-induced chronic kidney disease (CKD) young rat model. Six-week-old young Sprague Dawley rats of both sexes were fed a regular diet (C group), a diet supplemented with 0.5% adenine (CKD group), or adenine plus 0.01% melatonin in their drinking water (CKD + M group) for three weeks (N = 8/group). Adenine-fed rats developed renal dysfunction, hypertension, renal hypertrophy and increased uremic toxin levels of TMAO and ADMA. Melatonin therapy prevented hypertension in both sexes and attenuated kidney injury in males. Melatonin reversed the changes to the plasma TMAO-to-TMA ratio induced by CKD in both sexes. Besides, the protective effects of melatonin were associated with restoration of gut microbiota alterations, including increased α-diversity, and enhancement of the abundance of the phylum Proteobacteria and the genus Roseburia in male rats. Melatonin therapy also partially prevented the increases in ADMA in male CKD rats. Melatonin sex-specifically protected young rats against hypertension and kidney injury induced by CKD. The results of this study contribute toward a greater understanding of the interaction between melatonin, gut microbiota-derived metabolites, and the NO pathway that is behind CKD, which will help to prevent CKD-related disorders in children.

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