iTRAQ-Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha-1-Antitrypsin as Potential Biomarkers

Background. Chronic renal failure (CRF) has become a global health problem and bears a huge economic burden. FuShengong Decoction (FSGD) as traditional Chinese medicine has multiple pharmacological effects. Objectives. To understand the underlying molecular mechanism and signaling pathway involved in the FSGD treatment of CRF and screen differentially expressed proteins in rats with CRF treated with FSGD. Methods. Thirty-three male Sprague-Dawley rats were randomly divided into control group, CRF group, and FSGD group. Differentially expressed proteins were screened by iTRAQ coupled with nanoLC-MS/MS, and these identified proteins were later analyzed by GO, KEGG, and STRING. Additionally, haptoglobin (HP) and alpha-1-antitrypsin (AAT) were finally verified by ELISA, Western blot, and real time PCR. Results. A total of 417 proteins were identified. Nineteen differentially expressed proteins were identified in the FSGD group compared with the model group, of which 3 proteins were upregulated and 16 proteins were downregulated. Cluster analysis indicated that inflammatory response was associated with these proteins and complement and coagulation cascade pathways were predominantly involved. The validation methods further confirmed that the levels of HP and AAT were significantly increased. Conclusions. HP and AAT may be the important biomarkers in the pathogenesis of CRF and FSGD therapy.

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Serum-Derived Neuronal Exosomal miRNAs as Biomarkers of Acute Severe Stress

International Journal of Molecular Sciences ◽

10.3390/ijms22189960 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9960

Author(s):

Minkyoung Sung ◽

Soo-Eun Sung ◽

Kyung-Ku Kang ◽

Joo-Hee Choi ◽

Sijoon Lee ◽

...

Keyword(s):

Acute Stress ◽

Stress Hormones ◽

Differentially Expressed ◽

Control Group ◽

Severe Stress ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Exosomal Mirnas ◽

Differentially Expressed Mirnas ◽

Exosomal Mirna

Stress is the physical and psychological tension felt by an individual while adapting to difficult situations. Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed to determine whether differentially expressed miRNAs could be used as biomarkers of acute stress. Specifically, acute severe stress was induced in Sprague-Dawley rats via electric foot-shock treatment. In this acute severe-stress model, time-dependent changes in the expression levels of stress hormones and neuroinflammation-related markers were analyzed. In addition, nEVs were isolated from the serum of control mice and stressed mice at various time points to determine when brain damage was most prominent; this was found to be 7 days after foot shock. Next-generation sequencing was performed to compare neuronal exosomal miRNA at day 7 with the neuronal exosomal miRNA of the control group. From this analysis, 13 upregulated and 11 downregulated miRNAs were detected. These results show that specific miRNAs are differentially expressed in nEVs from an acute severe-stress animal model. Thus, this study provides novel insights into potential stress-related biomarkers.

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Altered norepinephrine turnover in the brain of rats with chronic renal failure.

Journal of the American Society of Nephrology ◽

10.1681/asn.v4111901 ◽

1994 ◽

Vol 4 (11) ◽

pp. 1901-1907

Author(s):

R Bigazzi ◽

E Kogosov ◽

V M Campese

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Locus Coeruleus ◽

Turnover Rate ◽

Nucleus Tractus Solitarius ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Norepinephrine Turnover ◽

Hypothalamic Nuclei ◽

And Control

Disturbances of the sympathetic nervous system have been described in chronic renal failure, but their role in the genesis and maintenance of hypertension frequently associated with this condition has not been established. The neuroadrenergic activity in brain nuclei involved in the regulation of blood pressure in uremic animals has also not been previously evaluated. In these studies, the neuroadrenergic activity was measured in the anterior, lateral, and posterior hypothalamic nuclei, in the locus coeruleus, and in the nucleus tractus solitarius of Sprague Dawley rats 5/6 nephrectomized or sham operated 4 wk before the experiments. Neuroadrenergic activity was determined by calculating norepinephrine (NE) turnover rate (in picograms per milligram per hour), 3, 6 and 12 h after inhibition of NE synthesis with L-methyltyrosine. The endogenous NE concentration was significantly greater in the posterior hypothalamic nuclei (21,501 +/- 1,777 pg/mg wet wt) and in the locus coeruleus (16,152 +/- 1,114 pg/mg wet tissue) of uremic compared with control rats (12,213 +/- 1,404 and 7,991 +/- 622 pg/mg wet wt, respectively). On the other hand, the endogenous NE content of the nucleus tractus solitarius and the anterior hypothalamic nuclei did not differ between uremic and control rats. The turnover rate of NE in the posterior hypothalamic nuclei of uremic rats (2150 +/- 430 pg/mg per hour) was significantly faster (P < 0.05) than in control rats (977 +/- 244 pg/mg per hour). The turnover rate of NE in the locus coeruleus of uremic rats (2,584 +/- 323 pg/mg per hour) was also significantly faster than in control animals (400 +/- 140 pg/mg per hour; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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Failure of Loading with Sodium Bicarbonate to Protect against Acute Renal Failure Induced by Mercuric Chloride in the Rat

Clinical Science ◽

10.1042/cs0530149 ◽

1977 ◽

Vol 53 (2) ◽

pp. 149-154 ◽

Cited By ~ 2

Author(s):

J. E. Beaumont ◽

T. A. Kotchen ◽

J. H. Galla ◽

R. G. Luke

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Renin Activity ◽

Sodium Balance ◽

Control Group ◽

Sprague Dawley ◽

Urinary Volume ◽

Sprague Dawley Rats

1. To investigate the mechanism by which sodium loading protects against acute renal failure we compared the effects of prior chronic loading with NaCl, or with NaHCO3, on renal function after injection of HgCl2. 2. Twenty-four male Sprague-Dawley rats were divided into three groups of eight rats. One group drank isotonic NaCl solution, a second drank isotonic NaHCO3 solution and the third control group drank deionized water. Acute renal failure was induced by HgCl2 on day 9, and the rats were killed 48 h after injection. 3. Net sodium balances and plasma volumes were similar in both groups of sodium-loaded rats. After HgCl2 serum creatinine was significantly less and urinary volume was greater in NaCl-loaded than in both NaHCO3-loaded and water-drinking animals. 4. Plasma renin activity of both NaCl- and NaHCO3-loaded animals was less than that of control rats. However, renal renin content was suppressed by NaCl but not by NaHCO3 loading. 5. Loading with NaCl afforded greater protection against HgCl2-induced acute renal failure than NaHCO3. Since this difference was not related to changes in sodium balance or plasma volume before HgCl2, or plasma renin activity after HgCl2, the results support the hypothesis that intrarenal renin plays a role in the pathogenesis of HgCl2-induced acute renal failure in the rat.

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High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

Cardiorenal Medicine ◽

10.1159/000446547 ◽

2016 ◽

Vol 6 (4) ◽

pp. 317-327 ◽

Cited By ~ 3

Author(s):

Pavlos Kashioulis ◽

Ola Hammarsten ◽

Niels Marcussen ◽

Emman Shubbar ◽

Aso Saeed ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Cardiac Troponin ◽

Troponin T ◽

Cardiac Injury ◽

Serum Levels ◽

Left Ventricular ◽

Sprague Dawley ◽

Small Artery ◽

Sprague Dawley Rats

Aims: To examine the effects of 2 weeks of high-NaCl diet on left ventricular (LV) morphology and serum levels of cardiac troponin T (cTnT) in rats with adenine-induced chronic renal failure (ACRF). Methods: Male Sprague-Dawley rats either received chow containing adenine or were pair-fed an identical diet without adenine [controls (C)]. Approximately 10 weeks after the beginning of the study, the rats were randomized to either remain on a normal NaCl diet (NNa; 0.6%) or to be switched to high-NaCl chow (HNa; 4%) for 2 weeks, after which acute experiments were performed. Results: Rats with ACRF showed statistically significant increases (p < 0.001) in arterial pressure (AP), LV weight and fibrosis, and serum cTnT levels compared to controls. Two weeks of high-NaCl intake augmented the increases in AP, LV weight and fibrosis, and serum cTnT concentrations only in ACRF rats (p < 0.05 for group × NaCl intake interaction). Compared to group C-NNa, cTnT levels were elevated approximately 6-fold in group ACRF-NNa and 24-fold in group ACRF-HNa. Focal LV injury with cardiomyocyte necrosis, scarring, and fibrinoid necrosis of small arteries were only detected in group ACRF-HNa. There was a strong correlation between the degree of LV fibrosis and serum cTnT levels in ACRF rats (r = 0.81, p < 0.01). Conclusion: Two weeks of high-NaCl diet in rats with ACRF produces LV injury and aggravates increases in serum cTnT levels, presumably by causing hypertension-induced small artery lesions leading to myocardial ischemia. This model may be suitable for studying pathophysiological mechanisms in chronic renicardiac syndromes.

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Biochemical changes in the pancreas of rats with chronic renal failure

AJP Renal Physiology ◽

10.1152/ajprenal.1985.249.4.f518 ◽

1985 ◽

Vol 249 (4) ◽

pp. F518-F523

Author(s):

G. A. Kaysen ◽

A. P. Majumdar ◽

M. A. Dubick ◽

G. D. Vesenka ◽

G. Mar ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

The Other ◽

Sprague Dawley ◽

Pancreatic Acini ◽

Cholecystokinin Octapeptide ◽

Dna And Rna ◽

Sprague Dawley Rats ◽

Cationic Trypsinogen ◽

Protease Inhibitory Activity

Chronic renal failure (CRF) was produced in female Sprague-Dawley rats by 7/8 nephrectomy. Creatinine clearance was depressed significantly (P less than 0.005) and blood urea nitrogen (BUN) increased in CRF rats when compared with the sham-operated (S) controls. CRF caused no apparent change in body weight but significantly increased pancreatic weight as well as increased DNA, RNA, and protein content. Pancreatic protein-to-DNA and RNA-to-DNA ratios were also found to be significantly higher in CRF rats than in the S controls. Trypsin-like activity and immunoreactive cationic trypsinogen levels were both increased in the pancreas of CRF rats, but not in their serum. On the other hand, protease inhibitory activity in the pancreas and serum was significantly decreased by CRF. The ability of the dispersed pancreatic acini isolated from CRF rats to incorporate [3H]-leucine into protein, in the absence and presence of 0.25 nM cholecystokinin octapeptide (CCK-8), was found to be lower than in the controls. Furthermore, discharge of both trypsinogen and chymotrypsinogen induced by CCK-8 was markedly reduced from acini of CRF rats as compared with the S controls. In contrast, lactate dehydrogenase (LDH) was released more readily from pancreatic acini of CRF. It is concluded that mild CRF produces hyperplasia and hypertrophy of the pancreas and lowers the responsiveness of acini to CCK-8 with respect to synthesis and secretion of proteins.

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Effect of Experimentally Induced Hepatic and Renal Failure on the Pharmacokinetics of Topiramate in Rats

BioMed Research International ◽

10.1155/2014/570910 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Kamal M. Matar ◽

Yasin I. Tayem

Keyword(s):

Renal Failure ◽

Pharmacokinetic Profile ◽

Treated Group ◽

Time Profile ◽

Control Group ◽

Sprague Dawley ◽

Elimination Phase ◽

Sprague Dawley Rats ◽

And Control ◽

Control Plasma

We aimed to investigate the effect of induced hepatic and renal failure on the pharmacokinetics of topiramate (TPM) in rats. Twenty-four Sprague-Dawley rats were used in this study. Renal or hepatic failure was induced by a single i.p. dose of 7.5 mg/kg cisplatin (n=8) or 0.5 mL/kg carbon tetrachloride (CCl4) (n=8), respectively. Three days after cisplatin dose or 24 h after CCl4dose, the rats were administered a single oral dose of 20 mg/kg TPM. The plasma samples were quantified by LC-MS/MS method. Compared to control, plasma concentration-time profile in CCl4-treated and, to a lesser extent, in cisplatin-treated rats decreased more slowly particularly in the elimination phase. TPM oral clearance (CL/F) in CCl4-treated group was significantly lower than that in control (P<0.001), whereasAUC0−∞, T1/2, and Vd/F were significantly higher in CCl4-treated rats compared to the control (P<0.01). The CL/F was not significantly different between cisplatin-treated rats and control (P>0.05). However, in cisplatin-treated rats, the T1/2 and Vd/F were significantly higher than that in the control group (P<0.01). Both conditions failed to cause a significant effect onCmaxorTmax. The present findings suggest that induced hepatic or renal failure could modify the pharmacokinetic profile of TPM in the rat.

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Skeletal Muscle Metabolomic Responses to Endurance and Resistance Training in Rats under Chronic Unpredictable Mild Stress

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041645 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1645

Author(s):

Xiangyu Liu ◽

Xiong Xue ◽

Junsheng Tian ◽

Xuemei Qin ◽

Shi Zhou ◽

...

Keyword(s):

Resistance Exercise ◽

Endurance Exercise ◽

Field Tests ◽

Treadmill Running ◽

Control Group ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Sprague Dawley ◽

Exercise Interventions ◽

Sprague Dawley Rats

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.

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Ranitidine as an alcohol dehydrogenase inhibitor in acute methanol toxicity in rats

Human & Experimental Toxicology ◽

10.1177/0960327109353777 ◽

2009 ◽

Vol 29 (2) ◽

pp. 93-101 ◽

Cited By ~ 8

Author(s):

Amal A El-Bakary ◽

Sahar A El-Dakrory ◽

Sohayla M Attalla ◽

Nawal A Hasanein ◽

Hala A Malek

Keyword(s):

Alcohol Dehydrogenase ◽

High Performance ◽

Negative Control Group ◽

Positive Control ◽

Negative Control ◽

Control Group ◽

Sprague Dawley ◽

Blood Samples ◽

Methanol Poisoning ◽

Sprague Dawley Rats

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.

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Effect of Proportional Reduction of Sodium Intake on the Adaptive Increase in Glomerular Filtration Rate/Nephron and Potassium and Phosphate Excretion in Chronic Renal Failure in the Rat

Clinical Science ◽

10.1042/cs0490193 ◽

1975 ◽

Vol 49 (3) ◽

pp. 193-200 ◽

Cited By ~ 2

Author(s):

C. H. Espinel

Keyword(s):

Renal Failure ◽

Glomerular Filtration Rate ◽

Chronic Renal Failure ◽

Glomerular Filtration ◽

Sodium Excretion ◽

Filtration Rate ◽

Sodium Intake ◽

Dietary Sodium ◽

Control Group ◽

Phosphate Excretion

1. The influence of dietary sodium intake on the glomerular filtration rate (GFR/nephron) and potassium and phosphate excretion was examined at three stages of progressive chronic renal failure produced in rats by sequential partial nephrectomies. 2. The adaptive increased sodium excretion per nephron in the control group receiving a constant sodium intake did not occur in the experimental group that had a gradual reduction of dietary sodium in direct proportion to the fall in GFR. 3. Despite the difference in sodium excretion, the increase in GFR/nephron, the daily variation in the amount of potassium and phosphate excreted, the increase in potassium and phosphate excretion per unit nephron, and the plasma potassium and phosphate concentrations were the same in the two groups. 4. The concept of ‘autonomous adaptation’ in chronic renal failure is presented.

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Mineralocorticoid Receptor Activation by Aldosterone or Corticosterone Induces Hypertension, Myocardial Infarction and Proteinuria

Hypertension ◽

10.1161/hyp.36.suppl_1.723-a ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 723-723

Author(s):

Qing-Feng Tao ◽

Diego Martinez vasquez ◽

Ricardo Rocha ◽

Gordon H Williams ◽

Gail K Adler

Keyword(s):

Myocardial Infarction ◽

Drinking Water ◽

Mineralocorticoid Receptor ◽

Critical Role ◽

Weight Ratio ◽

Myocardial Necrosis ◽

Receptor Activation ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

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