Metabolic syndrome (MS) is a constellation of metabolic derangements associated with vascular endothelial dysfunction and oxidative stress and is widely regarded as an inflammatory condition, ...accompanied by an increased risk for cardiovascular disease. The present study tried to investigate the implications of telomerase activity with inflammation and impaired endothelial function in patients with metabolic syndrome. Telomerase activity in circulating peripheral blood mononuclear cells (PBMC), TNF-α, IL-6 and ADMA were monitored in 39 patients with MS and 20 age and sex-matched healthy volunteers. Telomerase activity in PBMC, TNF-α, IL-6 and ADMA were all significantly elevated in patients with MS compared to healthy volunteers. PBMC telomerase was negatively correlated with HDL and positively correlated with ADMA, while no association between TNF-α and IL-6 was observed. IL-6 was increasing with increasing systolic pressure both in the patients with MS and in the healthy volunteers, while smoking and diabetes were positively correlated with IL-6 only in the patients' group. In conclusion, in patients with MS characterised by a strong dyslipidemic profile and low diabetes prevalence, significant telomerase activity was detected in circulating PBMC, along with elevated markers of inflammation and endothelial dysfunction. These findings suggest a prolonged activity of inflammatory cells in the studied state of this metabolic disorder that could represent a contributory pathway in the pathogenesis of atherosclerosis.
(1) Background: Various epidemiological studies suggest that oxidative stress and disrupted neuronal function are mechanistically linked to neurodegenerative diseases (NDs), including Parkinson's ...disease (PD) and Alzheimer's disease (AD). DNA damage, oxidative stress, lipid peroxidation, and eventually, cell death such as NDs can be induced by nitrosamine-related compounds, leading to neurodegeneration. A limited number of studies have reported that exposure to diethylnitrosamine (DEN), which is commonly found in processed/preserved foods, causes biochemical abnormalities in the brain. Artichoke leaves have been used in traditional medicine as a beneficial source of bioactive components such as hydroxycinnamic acids, cynarine, chlorogenic acid, and flavonoids (luteolin and apigenin). The aim of this study is to investigate the favorable effects of exogenous artichoke (Cynara scolymus) methanolic leaf extract supplementation in ameliorating DEN-induced deleterious effects in BALB/c mouse brains. (2) Methods: This study was designed to evaluate DEN (toxicity induction by 100 mg/kg) and artichoke (protective effects of 0.8 and 1.6 g/kg treatment) for 14 days. All groups underwent a locomotor activity test to evaluate motor activity. In brain tissue, oxidative stress indicators (TAC, TOS, and MDA), Klotho and PPARγ levels, and apoptotic markers (Bax, Bcl-2, and caspase-3) were measured. Brain slices were also examined histopathologically. (3) Results: Artichoke effectively ameliorated DEN-induced toxicity with increasing artichoke dose. Impaired motor function and elevated oxidative stress markers (decreasing MDA and TOS levels and increasing TAC level) induced by DEN intoxication were markedly restored by high-dose artichoke treatment. Artichoke significantly improved the levels of Klotho and PPARγ, which are neuroprotective factors, in mouse brain tissue exposed to DEN. In addition, caspase-3 and Bax levels were reduced, whereas the Bcl-2 level was elevated with artichoke treatment. Furthermore, recovery was confirmed by histopathological analysis. (4) Conclusions: Artichoke exerted neuroprotective effects against DEN-induced brain toxicity by mitigating oxidant parameters and exerting antioxidant and antiapoptotic effects. Further research is needed to fully identify the favorable impact of artichoke supplementation on all aspects of DEN brain intoxication.
Acute kidney injury (AKI) is associated with increased morbidity, prolonged hospitalization, and mortality, especially in high risk patients. Phosphodiesterase 5 inhibitors (PDE5Is), currently ...available as first-line therapy of erectile dysfunction in humans, have shown a beneficial potential of reno-protection through various reno-protective mechanisms. The aim of this work is to provide a comprehensive overview of the available literature on the reno-protective properties of PDE5Is in the various forms of AKI. Medline was systematically searched from 1946 to November 2019 to detect all relevant animal and human studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 83 studies were included for qualitative synthesis. Sildenafil is the most widely investigated compound (42 studies), followed by tadalafil (20 studies), icariin (10 studies), vardenafil (7 studies), zaprinast (4 studies), and udenafil (2 studies). Even though data are limited, especially in humans with inconclusive or negative results of only two clinically relevant studies available at present, the results of animal studies are promising. The reno-protective action of PDE5Is was evident in the vast majority of studies, independently of the AKI type and the agent applied. PDE5Is appear to improve the renal functional/histopathological alternations of AKI through various mechanisms, mainly by affecting regional hemodynamics, cell expression, and mitochondrial response to oxidative stress and inflammation.
Cardiac complications are common in carbon monoxide (CO) poisoning and associated with high morbidity and mortality. We have previously shown that erythropoietin (EPO) could reduce CO-induced cardiac ...ischemia in rat. In the current study, the anti-apoptotic effect of EPO during CO cardiotoxicity was investigated in order to elucidate the mechanism of EPO anti-ischemic action.
Wistar rats were exposed to CO (250, 1000 and 3000ppm). EPO (5000IU/kg) was administered to all groups by intraperitoneal injection at the end of CO exposure period. TUNEL and caspase-3 activity levels were assessed to investigate the effects of CO exposure and subsequent EPO administration on myocardial apoptosis. The changes of mitochondrial membrane potential (MMP) were also assessed with sensitive lipophilic dye JC-1 by flow cytometry. The roles of Bcl2 and Bax in EPO protective effect were investigated by Western blotting.
Myocardial apoptosis was observed following CO exposure. Moreover, mitochondrial membrane depolarization and significant reduction in Bcl2/Bax ratio were shown following CO poisoning especially at 3000ppm. On the other hand, EPO administration could effectively suppress apoptosis in myocardial cells. Also, EPO significantly prevented the CO-induced depolarization of MMP (p<0.001) and preserved Bcl2/Bax ratio (p<0.01).
EPO reduces myocardial injury due to CO intoxication. Thus EPO could be suggested as a possible candidate for the management of CO cardiotoxicity with clinical applications.
(1) Background: Human health risks and hazards from chemical substances are well regulated internationally. However, cardiotoxicity, is not defined as a stand-alone hazard and therefore there are no ...defined criteria for the classification of substances as cardiotoxic. Identifying and regulating substances that cause cardiovascular adverse effects would undoubtedly strengthen the national health systems. (2) Methods: To overcome the aforementioned gap, a roadmap is proposed for identifying regulatory criteria from animal studies and endorse legislation in order to classify substances as cardiotoxic. The roadmap consists of: (i) the identification of the appropriate animal species and strains; (ii) the identification of the lines of scientific evidence (e.g., histopathological, biochemical and echocardiographic indices etc.) from animal studies with relevance to humans; (iii) the statistical analysis and meta-analysis for each line of scientific evidence after exposure to well-established cardiotoxicants to humans (e.g., anthracyclines) in order to identify threshold values or range of normal and/ or altered values due to exposure; (iv) validation of the above described lines of evidence in animals exposed to other alleged cardiotoxic substances (e.g., anabolic androgen steroids (AAS) and pesticides); (v) establishment of mechanisms of action based on information of either known or alleged cardiotoxicants; and (vi) introduction of novel indices and in silico methods. (3) Results: Preliminary results in rats indicate a clear distinction from normal values to values measured in rats exposed to anthracyclines regarding left ventricle (LV) fractional shortening (FS) and LV ejection fraction (EF). A distinctive pattern is similarly observed for Creatine Kinase-Myocardial Band isoenzyme (CK-MB) and cardiac tissue glutathione (GSH). These findings are encouraging and indicate that there is room for targeted research to this end, and that these specific indices and biochemical markers should be further investigated in order to be developed to regulatory criteria. (4) Conclusions: Further research should be conducted by both the scientific and regulatory community that aims to clearly define the cardiotoxicity hazard caused by chemicals and develop a full set of scientific criteria.
(1) Background: Doxorubicin (DOX) is extensively used for cancer treatments; however, its clinical application is limited because of its cardiotoxic adverse effects. A combination of DOX and agents ...with cardioprotective properties is an effective strategy to ameliorate DOX-related cardiotoxicity. Polyphenolic compounds are ideal for the investigation of novel cardioprotective agents. Chlorogenic acid (CGA), an essential dietary polyphenol found in plants, has been previously reported to exert antioxidant, cardioprotective, and antiapoptotic properties. The current research evaluated CGA's in vivo cardioprotective properties in DOX-induced cardiotoxicity and the probable mechanisms underlying this protection. (2) Methods: CGA's cardioprotective properties were investigated in rats that were treated with CGA (100 mg/kg, p.o.) for fourteen days. The experimental model of cardiotoxicity was induced with a single intraperitoneal (15 mg/kg i.p.) injection of DOX on the 10th day. (3) Results: Treatment with CGA significantly improved the DOX-caused altered cardiac damage markers (LDH, CK-MB, and cTn-T), and a marked improvement in cardiac histopathological features accompanied this. DOX downregulated the expression of Nrf2/HO-1 signaling pathways, and the CGA reversed this effect. Consistently, caspase-3, an apoptotic-related marker, and dityrosine expression were suppressed, while Nrf2 and HO-1 expressions were elevated in the cardiac tissues of DOX-treated rats after treatment with the CGA. Furthermore, the recovery was confirmed by the downregulation of 8-OHdG and dityrosine (DT) expressions in immunohistochemical findings. (4) Conclusions: CGA demonstrated a considerable cardioprotective effect against DOX-induced cardiotoxicity. One of the possible mechanisms for these protective properties was the upregulation of the Nrf2/HO-1-dependent pathway and the downregulation of DT, which may ameliorate oxidative stress and cardiomyocyte apoptosis. These findings suggest that CGA may be cardioprotective, particularly in patients receiving DOX-based chemotherapy.
Cinnamon effect on blood pressure remains controversial. The present pilot study assessed cinnamon effect on blood pressure, and metabolic profile of stage 1 hypertension patients (S1HTN).
This ...double-blind placebo-controlled randomized trial was conducted between June and October 2019, in Mashhad, Iran. Study inclusion criteria comprised S1HTN diagnosis, based on 24-hour ambulatory blood pressure monitoring (ABPM). Subjects were randomly assigned to two groups: cinnamon group (capsule, 1500 mg/day, 90 days) and placebo group. On days 0 and 90, ABPM derived systolic and diastolic blood pressure (SBP and DBP, respectively), blood lipid profile, and fasting blood sugar (FBS) were recorded.
The two groups did not differ significantly regarding vascular risk factors, educational status, lipid profile and blood pressure at baseline, except for lower HDL-c in cinnamon group (p=0.03). On day 90, there was no significant difference between two study groups for lipid profile and blood pressure. A statistically significant decrease in mean 24-hr SBP and mean day SBP was observed in the cinnamon group, while mean night SBP and mean night DBP were decreased significantly in the placebo group after 90 days. A statistically significant decrease in mean change of day value of SBP was found in the cinnamon group, compared to the placebo. On day 90, FBS remained practically unchanged but a significant increase in HDL-c (5.8 unit; p=0.01) and a significant decrease in LDL-c levels (17.7 unit; p=0.009) were observed in the cinnamon group compared to placebo group.
Cinnamon caused a statistically significant decrease in mean ambulatory SBP but in a clinically moderate way, and lipid profile was significantly improved. Therefore, cinnamon might be considered a complementary treatment in subjects with S1HTN.
Taxifolin (TXF) is a flavonoid found abundantly in citrus/onion. Encouraging results on its renoprotective effect have been reported in a limited number of drug-induced nephrotoxicity animal models. ...The present study aimed to evaluate for the first time the potential renoprotective effects of TXF in a paracetamol (PAR)-induced nephrotoxicity rat model.
Rats were divided into three equal groups (
= 6 animals per group). Group 1 (PAR group, PARG) received PAR diluted in normal saline by gavage (1000 mg/kg). Group 2 (TXF group, TXFG) received TXF diluted in normal saline by gavage (50 mg/kg) one hour after PAR administration. Group 3 (control group, CG) received normal saline. Twenty-four hours after PAR administration, all animals were sacrificed using high-dose anesthesia. Blood samples were collected and kidneys were removed.
The serum blood urea nitrogen, creatinine levels and serum malondialdehyde levels were significantly increased in the PARG. The serum glutathione peroxidase, glutathione reductase and total glutathione levels were significantly higher in the TXFG. At the same time, the kidneys of the PARG animals demonstrated tubular epithelium swelling, distension and severe vacuolar degeneration. The kidneys of the TXFG animals showed mildly dilated/congested blood vessels.
The TXF renoprotective effects are promising in preventing PAR-induced nephrotoxicity, mainly through antioxidant activity, and warrant further testing in future studies.
The aim of our study was to assess the effect of 8 weeks of pulmonary rehabilitation (PR) in patients with pulmonary embolism (PE) during unsupervised PR (unSPR
) versus supervised PR (SPR
) on ...cardiopulmonary exercise testing (CPET) parameters, sleep quality, quality of life and cardiac biomarkers (NT-pro-BNP). Fourteen patients with PE (unSPR
, n = 7, vs. SPR
, n = 7) were included in our study (age, 50.7 ± 15.1 years; BMI, 30.0 ± 3.3 kg/m
). We recorded anthropometric characteristics and questionnaires (Quality of life (SF-36) and Pittsburg sleep quality index (PSQI)), we performed blood sampling for NT-pro-BNP measurement and underwent CPET until exhausting before and after the PR program. All patients were subjected to transthoracic echocardiography prior to PR. The SPR
differed in mean arterial pressure at rest before and after the PR program (87.6 ± 3.3 vs. 95.0 ± 5.5, respectively,
= 0.010). Patients showed increased levels of leg fatigue (rated after CPET) before and after PR (
= 0.043 for SPR
,
= 0.047 for unSPR
) while the two groups differed between each other (
= 0.006 for post PR score). Both groups showed increased levels in SF-36 scores (general health;
= 0.032 for SPR
,
= 0.010 for unSPR
; physical health;
= 0.009 for SPR
,
= 0.022 for unSPR
) and reduced levels in PSQI (cannot get to sleep within 30-min;
= 0.046 for SPR
,
= 0.007 for unSPR
; keep up enough enthusiasm to get things done;
= 0.005 for SPR
,
= 0.010 for unSPR
) following the PR program. The ΝT-pro-BNP was not significantly different before and after PR or between groups. PR may present a safe intervention in patients with PE. The PR results are similar in SPR
and unSPR
.
Etiology of Renal Replacement Therapy in Iran Morovatdar, Negar; Tayebi Nasrabad, Gholamreza; Tsarouhas, Konstantinos ...
International journal of nephrology,
2019, Letnik:
2019
Journal Article
Recenzirano
Odprti dostop
Introduction. End-stage renal disease (ESRD) is one of the most common life-threatening diseases. In the past two decades, several factors were held responsible as the cause of this condition. The ...present study aimed to determine the causes of ESRD in the province of Khorasan Razavi, Iran. Materials and Methods. This cross-sectional study was conducted on 2404 ESRD patients who referred to 39 hemodialysis centers in Khorasan Razavi province, Iran, and were registered in the Mashhad University of Medical Sciences (MUMS), between 2000 and December 2018. Sociodemographic data and causes of ESRD were extracted from data registry. Results. The mean age at onset of hemodialysis for 2404 patients was 52.8 ± 16.4 years, and 57.1% of the patients were male. Clinical profile of hypertension (28.3%) and diabetes mellitus (24.8%) were the most common known causes of ESRD in our patients. Hypertension was more prevalent in male patients compared with females (30 vs 25%, respectively) while diabetes was more prevalent in females compared with males (25.4 vs 24.4%, respectively), p=0.009. Educational level was significantly associated with the cause of ESRD (p<0.001). Age of onset of ESRD in hypertensive patients was significantly lower compared with diabetic patients (51.5 ± 16.3 vs 58.28 ± 12.9 years, respectively; p<0.001). Conclusions. In the current study, the most common causes of ESRD were hypertension and diabetes mellitus. Primary prevention of hypertension and diabetes and proper treatment must be considered to reduce the burden of ESRD in Iran.
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