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Context. Endothelial dysfunction and diabetic cardiomyopathy are critical complications of diabetes. Gallic acid (GA) plays a significant role in cardiovascular disorders resulted from diabetes. In addition, increased plasma miR-24, miR-126 associated with endothelial dysfunction. Aim. The current study was designed to assess the effects of GA on plasma miR-24, miR-126 levels in the diabetic rats. Animals and Methods. Adult male Sprague-Dawley rats were divided into three groups (n=8): control (C), diabetic (D) and diabetic group treated with GA (D+G, 25 mg/kg, by gavage) for eight weeks. The blood glucose level, body weight, lipid profile, blood pressure, plasma miR-24 and miR-126 levels, antioxidant and inflammatory biomarkers were measured. Results. The plasma levels of miR-24, miR-126, body weight, high-density lipoprotein cholesterol (HDL-c), total anti-oxidant capacity (TAC) and the systolic blood pressure significantly reduced and blood glucose, total cholesterol (TC), triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-c), malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and low-density lipoprotein cholesterol (LDL-c) significantly elevated among the diabetic rats compared with the control group. However, GA restored body weight, blood pressure, TC, TG, VLDL-c, TNF-a, miR-126, blood glucose, HDL-c, MDA, TAC, miR-24 and IL-6 among the GA treated rats compared with the diabetic group. Conclusion. GA improves inflammation, oxidative stress and hypotension result from diabetes. These protective effects are probably mediated via increasing plasma miR-24 and miR-126 levels. [ABSTRACT FROM AUTHOR]

Background This study aimed to evaluate the role of H2S on gastric emptying rate ( GER) and also to determine the effect of gastric distention on mRNA and protein expression of cystathionine β-lyase ( CBS) and cystathionine γ-synthase ( CSE) in diabetic-gastroparetic and normal rats. Methods Adult normal rats intraperitoneally received either propargylglycine ( PAG), L-cysteine or Na HS 30 min prior to GER marker (acetaminophen) to investigate H2S involvement in GER and the same protocols were performed in diabetes-induced gastroparesis rats. The role of calcitonin gene related peptide ( CGRP) neurons in the prokinetic effect of endogenous H2S on GER was determined. The level of CBS and CSE expressions in response to gastric distention were also determined. The effect of H2S on frequency and tension of spontaneous contractions of gastric smooth muscle strips was investigated. Key Results Our results showed that: (i) H2S and L-cysteine increased GER in gastroparetic and normal rats. (ii) The increased levels of CSE expression in response to gastric distention in diabetic rats were lower than in normal rats. (iii) PAG inhibited the excitatory effect of capsaicin on GER and on tension of spontaneous contractions of strips. (iv) Hydrogen sulphide increased the frequency and tension of spontaneous contractions of gastric strip muscles in normal and diabetic rats. Conclusions & Inferences The results showed that delayed GER in diabetic rats can be due to down-regulation of H2S biosynthesis enzyme, CSE and suggested that a potential prokinetic role for H2S to treat the delayed gastric emptying in diabetic patients. [ABSTRACT FROM AUTHOR]

Cisplatin nephrotoxicity is a well-known emergency clinical condition caused by oxidative stress and inflammation. Naringin (NAR) is considered an antioxidant agent with renoprotective effects capable of removing reactive oxygen species. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) are reported to have anti-inflammatory and antioxidant properties. The present research examined the renoprotective effect of the combination of NAR and AD-MSCs as opposed to each one alone on cisplatin-induced nephrotoxicity through SIRT-1/Nrf-2/HO-1 pathway. This study included five groups (n = 8 each) of male Sprague-Dawley rats (200 - 220 g): sham, cisplatin: rats receiving cisplatin (6.5 mg/kg, i.p.) on the 4th day; NAR+cisplatin: rats pretreated with NAR (1 week, i.p.) + cisplatin on the 4th day; AD-MSCs: rats receiving AD-MSCs (1 × 10 6 ) by injection through the tail vein on the 5th day + cisplatin on the 4th day; and NAR+AD-MSCs+cisplatin. On the 8th day, the animals were anesthetized to obtain tissue and blood samples. Biochemical factors, inflammation, oxidative stress, and gene expression were explored. Cisplatin increased blood urea nitrogen, creatinine, inflammation, and oxidative stress. Moreover, mRNA expression of Sirtuin1, nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (HO-1) remarkably reduced. Furthermore, cisplatin led to a disturbance in kidney structure (glomerular atrophy, cell infiltrations, and tubular dysfunction) as confirmed by histology findings. However, NAR pretreatment, AD-MSC administration, or a combination of both significantly reversed these changes. Overall, when used together, NAR and AD-MSCs had stronger cisplatin-induced effects on kidney dysfunction by inhibiting inflammation, reducing oxidative stress, and increasing the Sirtuin1/Nrf-2/HO-1 pathway., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play a vital role in myocardial ischemia/reperfusion (I/R) injury. This enzyme may affect sarcoplasmic reticulum Ca 2+ ATPase (SERCA2), ryanodine receptor (RyR2) and sodium/calcium exchanger (NCX1) during myocardial ischemia/reperfusion injury. The objective of this investigation was to analyze the effects of the combination of GSK650394 (SGK1 inhibitor) and gallic acid on the calcium ions regulation, inflammation, and cardiac dysfunction resulting from ischemia/reperfusion (I/R) injury in the heart. Sixty male Wistar rats were randomly divided into six groups, pretreated with gallic acid or vehicle for 10 days. Then the heart was isolated and exposed to I/R. In the SGK1 inhibitor groups, GSK650394 was infused 5 min before ischemia induction. After that, Ca 2+ homeostasis, inflammatory factors, cardiac function, antioxidant activity, and myocardial damage were evaluated. The findings suggested that the use of two drugs in combination therapy produced more significant improvements in left ventricular end diastolic pressure, left ventricular systolic pressure, RR-interval, ST-elevation, inflammation factors, and antioxidant enzymes activity as compared to the use of each drug. Despite this, there was a significant decrease observed in heart marker enzymes (including lactate dehydrogenase (LDH), troponin-I (cTn-I), creatine kinase-MB (CK-MB) and creatine phosphokinase (CPK) when compared to the ischemic group. Additionally, the expression of RyR2, NCX1, and SERCA2 genes showed a noteworthy increase as compared to the ischemic group. The findings of this study propose that using both of these agents on myocardial I/R injury could have superior advantages compared to using only one of them., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Methotrexate-induced nephrotoxicity is a medical emergency which is associated with a variety of side effects. Vanillic acid (VA), as an antioxidant, removes free radical oxygen to protect cell defense. Therefore, this study investigated VA's beneficial effects on nephrotoxicity induced by methotrexate through its anti-apoptosis, antioxidant, and anti-inflammatory properties. Our study included five groups of male Wistar rats (n = 8): sham, MTX (Methotrexate) group: rats receiving methotrexate (20 mg/kg, intraperitoneally) on Day 2. Moreover, the remaining groups consisted of animals that received vanillic acid (25, 50, and 100 mg/kg, orally for seven days) plus MTX on the 2 nd day. The rats were deeply anesthetized on the eighth day to obtain blood and renal tissue samples. The results showed that MTX can increase blood urea nitrogen and creatinine. However, VA (50 and 100 mg/kg) improved renal function as approved by histological findings. Compared with MTX-treated rats, VA enhanced the contents of total antioxidant capacity (TAC) and reduced renal malondialdehyde (MDA). Moreover, VA reduced mRNA expressions of caspase-3 and Bcl-2-associated x protein (Bax) and caused mRNA overexpression of the renal B-cell lymphoma-2 (Bcl-2), and Nrf-2 (Nuclear factor erythroid 2-related factor 2) compared to the MTX group. Also, VA administration significantly reduced inflammatory agents. Overall, VA protects the kidneys against methotrexate-induced nephrotoxicity via anti-apoptosis, antioxidant, and anti-inflammatory properties. Our results revealed that the most effective dose of VA was 100 mg/kg., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: Shortness of breath and syncope are common symptoms of right ventricular failure caused by pulmonary arterial hypertension (PAH), which is the result of blockage and increased pressure in the pulmonary arteries. There is a significant amount of evidence supporting the idea that inflammation and vascular calcification (VC) are important factors in PAH pathogenesis. Therefore, we aimed to investigate the features of the inflammatory process and gene expression involved in VC in monocrotaline (MCT)-induced PAH rats. MCT (60 mg/kg, i.p.) was used to induce PAH. Animals were given normal saline or rosmarinic acid (RA) (10, 15, and 30 mg/kg, gavage) for 21 days. An increase in right ventricular systolic pressure was evaluated as confirming PAH. To determine the level of inflammation in lung tissue, pulmonary edema and the total and differential white blood cell counts in the bronchoalveolar lavage fluid were measured. Also, the expression of NFκB, OPG, Runx2, and P-selectin genes was investigated to evaluate the level of VC in the heart. Our experiment showed that RA significantly decreased right ventricular hypertrophy, inflammatory factors, NFκB, Runx2, and P-selectin gene expression, pulmonary edema, total and differential white blood cell count, and increased OPG gene expression. Therefore, our research showed that RA protects against MCT-induced PAH by reducing inflammation and VC in rats., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Right ventricular hypertrophy (RVH) often results in failure of the right ventricle or even the left ventricle. Rosmarinic acid (RA), a natural polyphenol, is commonly found in Boraginaceae species and some species of ferns and hornworts. This study looked at how RA affects oxidative stress and left ventricular hemodynamic functions as well as RVH in monocrotaline (MCT) induced RVH model rats., Materials and Methods: To cause RVH, MCT (60 mg/kg) was intraperitoneally (IP) injected. Rats were given saline or RA (10, 15, and 30 mg/kg, gavage, over 21 days). In anesthetized rats, the lead II electrocardiogram was recorded. The hemodynamic functions of the isolated heart were measured using the Langendorff apparatus (at constant pressure). Investigations were made into the right ventricular hypertrophy index (RVHI), the activities of superoxide dismutase, catalase, glutathione, and Wnt and β-catenin gene expressions in the left ventricle. H&E staining was used., Results: A significant decline in electrocardiogram parameters and anti-oxidant enzyme activities, an increase in QTc (Q-T corrected) intervals, MDA (Malondialdehyde), RVHI, and Wnt/β-catenin gene expression, and also significant changes in the hemodynamic parameters were demonstrated in the MCT group. RA improved the above-mentioned factors., Conclusion: According to the findings, RA may act as a cardioprotective agent against cardiovascular complications brought on by RVH due to its capacity to boost the activity of cardiac anti-oxidant enzymes and decrease the expression of genes involved in vascular calcification., Competing Interests: All authors declare no conflicts of interest.

Exposure to dust storm particulate matter (PM) is detrimental to kidney tissue. In this study, the impacts of chronic intake of dusty PM were explored as a major objective in a specified compartment to make a real-like dust storm (DS) model, and the role of hesperidin (HSP) as an antioxidant on kidney tissue was assessed in rats. Thirty-two male Wistar rats (200-220 g) were randomly allocated into 4 groups: CA+NS: (clean air and normal saline as a vehicle of HSP). Dusty PM and NS (DS+NS). HSP+ CA: rats received 200 mg/kg of HSP by gavage for 28 days, once daily in addition to exposure to clean air. HSP+DS: HSP plus DS. In DS groups, the animals were exposed to dust storms at a concentration of 5000-8000 μg/m 3 in the chamber for 1 h daily, for 4 consecutive weeks, except Thursdays and Fridays. At the end of the experiment, the animals were sacrificed for biochemical, inflammatory, oxidative stress, molecular parameters, and histological evaluation. DS significantly enhanced blood urea nitrogen and creatinine, inflammatory (tumor necrosis factor-α, and interleukin-1β), and oxidative stress indexes. Likewise, a significant increase was seen in mRNA Smads, collagen-I, and transforming growth factor-β1 (TGF-β1) expressions in the kidney. Histological findings showed contracted glomeruli and kidney structure disorder. In addition, Masson's trichrome staining demonstrated renal fibrosis. Nevertheless, HSP could significantly reverse these changes. Our data confirmed that DS results in kidney fibrosis through enhancing Smads/TGF-β1 signaling. However, HSP was able to inhibit these changes as confirmed by histological findings., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play an important role in ischemic-reperfusion (I/R) injury and myocardial dysfunction. Although many studies have been conducted on individual antioxidants, little attention has been paid to the effects of co-administration of an antioxidant with an SGK1 inhibitor on cardiac function after I/R., Methods: This study aimed to determine the effects of gallic acid (as an antioxidant) combined with an SGK1 inhibitor on I/R-induced cardiac dysfunction and inflammation. Sixty male Wistar rats were randomized into 6 groups, pretreated with gallic acid or vehicle for 10 days. Subsequently, the heart was isolated and exposed to I/R. In groups that received the SGK1 inhibitor, the heart was perfused with the SGK1 inhibitor GSK650394, 5 min before induction of ischemia. After that, cardiac function, inflammatory factors, and myocardial damage were evaluated., Results: The combination of these two compounds improved cardiac contractility, heart rate, rate pressure product, left ventricular developed pressure, left ventricular systolic pressure, perfusion pressure, and QRS voltage significantly (P < 0.05). In addition, concomitant therapy of these two agents reduced tumor necrosis factor-alpha and interleukin-6, and the activity of creatine kinase-MB, lactate dehydrogenase, and troponin-I (P < 0.05)., Conclusion: The results indicated that administration of gallic acid with the SGK1 inhibitor may have a potentiating effect on the improvement of cardiac dysfunction and I/R-induced inflammation., Competing Interests: The authors have no relevant financial or non-financial interests to disclose.

Objectives: Oxidative stress and serum and glucocorticoid-induced Kinase 1 gene (SGK1) perform a central role in the consequences of ischemia in the heart. This research aimed to investigate the effect of coadministration of gallic acid and the GSK650394 (as SGK1 gene inhibitor) on the ischemic complications of a rat model of cardiac ischemia/reperfusion (I/R) injury., Materials and Methods: Sixty male Wistar rats were divided into 6 groups with or without pretreatment with gallic acid for 10 days. After that, the heart was isolated and perfused with Krebs-Henseleit solution. A 30 min of ischemia was performed followed by a 60 min reperfusion. In 2 groups, GSK650394 was infused 5 min before ischemia induction. Ten minutes after reperfusion commencement, cardiac marker enzyme (CK-MB, LDH, and cTn-I) activities were measured in the cardiac perfusate. At the end of reperfusion, the activity of anti-oxidant enzymes (Catalase, Superoxide dismutase, and Glutathione peroxidase), lipid peroxidation (MDA), total anti-oxidant capacity (TAC), intracellular reactive oxygen species (ROS), infarct size, and SGK1 gene expression were measured in the heart tissue., Results: The results indicated that dual therapy with both drugs significantly improved endogenous anti-oxidant enzyme activity and TAC more than each drug alone. However, the heart marker enzymes (CK-MB, LDH, and cTn-I), MDA, ROS, infarct size, and SGK1 gene expression were reduced significantly compared with the ischemic group., Conclusion: The results of this study suggest that concomitant administration of both drugs in the case of cardiac I/R injury may have a more beneficial effect than each one alone., Competing Interests: The authors have no relevant financial or non-financial interests to disclose.

Competing Interests: None.

Objective: The kidney is well-known as the vital organ which is responsible for maintaining body homeostasis and secretion of toxic metabolites. Renal injury is accompanied by oxidative stress which results in cellular apoptosis, lipid peroxidation, and reduction of antioxidant levels. Plant extracts and their phytoconstituents, owing to free radical scavenging properties, seem to be valuable against modern synthetic and chemical drugs. Naringin is a flavonoid present in citrus fruits with pharmacologic effects including antioxidant, anti-inflammatory, and anti-apoptotic properties. This review summarizes the renoprotective effects of naringin and discusses mechanisms of its action against renal injury., Materials and Methods: For this paper, original subject-related articles published up to October 2020 have been reviewed in the databases, including PubMed, Scopus, and Web of Science, and Google Scholar., Results: Naringin increases antioxidant enzyme activity, and glutathione content, reduces lipid peroxidation and inhibits inflammatory cytokines. In the molecular investigation, naringin activates the Nrf-2 signaling, prevents apoptosis signaling, and inhibits the autophagy pathway. Besides, naringin could protect the kidney through modulating microRNA-10a in the kidney tissue in an acute kidney injury model., Conclusion: This review recommends that naringin can be considered a promising candidate to treat kidney dysfunction induced by oxidative stress in the future., Competing Interests: The authors have declared that there is no conflict of interest.

Cisplatin, an antineoplastic drug used in cancer therapy, -induced nephrotoxicity mediated by the production of reactive oxygen species (ROS). Gallic acid (GA) is identified as an antioxidant substance with free radical scavenging properties. This research was designed to examine the ameliorative impact of GA caused by cisplatin-induced nephrotoxicity through apoptosis and long non-coding RNA (lncRNA) Taurine-upregulated gene 1 (TUG1) expression. Thirty-two male Sprague Dawley rats (200 - 220 g) were randomly allocated to four groups: (1) control group; (2) rats treated with cisplatin (7.5 mg/kg, i.p.) on the fourth day; and the two other groups include rats pretreated with GA (20 and 40 mg/kg by gavage) for s7 days and cisplatin (7.5 mg/kg, i.p.) at the fourth day. The rats were anesthetized and sacrificed for collecting samples, 72 h after cisplatin administration. The blood samples were used to investigate biochemical factors and kidney tissue was evaluated for measuring oxidative stress and inflammatory factors and the gene expression of molecular parameters. The results indicated that GA administration increased the B-cell lymphoma-2 (Bcl-2) mRNA and lncRNA TUG1 expression, and reduced Bcl-2-associated x protein (Bax), and caspase-3 expression. Likewise, the TAC level increased, and kidney MDA content decreased by administration of GA. GA also decreased the inflammatory factor levels, including IL-1β and TNF-α. Moreover, GA led to the improvement of kidney dysfunction as evidenced by reducing plasma BUN (blood urea nitrogen) and Cr (creatinine). Taken together, GA could protect the kidney against cisplatin-induced nephrotoxicity through antioxidant, anti-inflammatory, and anti-apoptosis properties and reduction of lncRNA TUG1 expression., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hyperlipidemia is a common metabolic disorder in the general population, which may arise in hypothyroidism. Apelin is an endogenous ligand that acts as an adiponectin, and is involved in energy storage and metabolism. This study evaluated the effects of apelin administration per se or in combination with T4 on the serum level of thyroid-stimulating hormone (TSH), body weight, and lipid profile, along with the serum level of apelin, and its mRNA expression in heart, in 6-propyl-2-thiouracil (PTU)-induced hypothyroid rats. Male Wistar rats were assigned to five different groups: control, H (hypothyroid), H+A, H+T, and H+A+T. All groups except the control one received PTU (0.05%) in the drinking water for 6 weeks. In addition to PTU, the H+A, H+T, and H+A+T groups received apelin (200 μg/kg/day, i.p.), l-thyroxin (T4) (20 μg/kg/day, via gavage tube), and apelin+T4 during the last 14 days of the trial, respectively. A combined application of T4 and apelin in the H+A+T group effectively diminished mean TSH level, low-density-lipoprotein cholesterol/high-density-lipoprotein cholesterol ratio, and atherogenic index in these animals when compared with these values for the H group. Coadministration of apelin with T4 may offer valuable therapeutic benefits, specifically lowering blood plasma TSH, lipid disorder, and atherosclerosis biomarkers in PTU-induced hypothyroid rats., (© 2021 International Union of Biochemistry and Molecular Biology, Inc.)

Objectives: Exposures to particulate matter (PM) have been related to increased risk for cardiovascular health effects and can promote cardiac ischemia and oxidative stress. Crocin has strong antioxidant properties and stress-reducing effects. Therefore, this study considered the effect of crocin on cardiovascular parameters in rats exposed to PM 10 ., Materials and Methods: Forty Wistar rats (male, 250-300 g) were grouped as control, receiving normal saline and crocin, receiving PM 10 , receiving PM 10 +Crocin. Instillation of PM 10 into the trachea was done. Forty-eight hours after exposure to the normal saline or PM, the heart was separated. Hemodynamic and electrophysiological factors were measured. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase activity (CAT), malondialdehyde (MDA), xanthine oxidase, were evaluated by kits., Results: The voltage of the QRS complex was significantly reduced and PR and QTc intervals increased in PM 10 groups. Hemodynamic parameters before ischemia and in the ischemic-reperfusion stage, in the PM 10 group, showed a significant decrease. In the ischemic hearts of the PM 10 group, a significant decline in the activity of CAT, SOD, and GPx, and a significant increase in MDA and XOX enzymes activity were observed, and crocin improved all of these factors., Conclusion: Cardiac ischemia causes abnormal hemodynamic factors of the heart, which are exacerbated by PM 10 and further reduce the heart's contractile strength. Increased oxidative stress due to PM 10 is probably one of the important reasons for these changes. This study suggests that the use of antioxidants such as crocin improves the cardiovascular adverse effects of myocardial ischemia and PM 10 exposure., Competing Interests: The authors declare no conflicts of interest.

Context: The hyperglycemia (Hyper) induces oxidative stress in kidney tubular cells. Myricitrin (Myr) has an antioxidant effect along with low bioavailability., Objective: The present research investigated the effects of Myr and its solid lipid nanoparticles (SLN) on isolated proximal tubules exposed to the hyperglycemic condition., Materials and Methods: In this experimental study, the proximal tubules of mice were dissected by the microdissection method and the tubules were prepared for experimental or Real Time-PCR measurement., Results: The malondialdehyde level, transforming growth factor-β, nuclear factor kappa B and Bax genes expression increased in Hyper and decreased in Hyper + Myr and its SLN-treated groups compared to Hyper. Superoxide dismutase, total antioxidant capacity, the viability of proximal tubules and Bcl-2 gene expression decreased in untreated Hyper and increased in all treatment groups compared to Hyper., Conclusion: The hyperglycemia-induced oxidative disorder, inflammation and apoptosis in proximal tubules and that administrating Myr and its SLN improved them.

Emphysema is associated with an abnormal airspace enlargement distal to the terminal bronchioles accompanied by destructive changes in the alveolar walls and chronic inflammation. Air pollution can cause respiratory diseases such as chronic obstructive pulmonary disease (COPD) and emphysema in urban areas. As a natural antioxidant compound, gallic acid may be effective in controlling inflammation and preventing disease progression. In this research, we investigated the protective role of gallic acid in the inflammatory process and the possible signaling pathway in the elastase-induced emphysema. Forty-eight rats were divided into six different groups including the following: control, gallic acid (7.5, 15, and 30 mg/kg), porcine pancreatic elastase (PPE), and PPE+gallic acid 30 mg/kg. Oxidative stress indexes such as malondialdehyde and antioxidant enzyme activity were measured in all groups. The gene expression levels of heme oxygenase-1 (HO-1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined as key regulators of antioxidant and inflammation system. The PPE group showed pulmonary edema and a significant change in arterial blood gas values, which was associated with decreased antioxidant activity of enzymes and changes in NF-κB, HO-1, and Nrf2 gene expression in comparison to the control group. Co-treatment with gallic acid preserved all these changes approximately to the normal levels. The results confirmed that elastase-induced emphysema leads to lung injuries, which are associated with oxidative stress and inflammation. Also, the results suggested that gallic acid as a natural antioxidant agent can modulate the Nrf2 signaling pathway to protect the lung against elastase-induced emphysema. Therefore, we documented the evidence for the importance of NF-κB inhibitors and Nrf2 activators as a target for new treatments in respiratory dysfunction caused by oxidative agents., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: From the beginning of the COVID-19 pandemic, the development of infrastructures to record, collect and report COVID-19‏ ‏data has become a fundamental necessity in the world. The disease registry system can help build an infrastructure to collect data systematically. The study aimed to design a minimum data set for the COVID-19 registry system., Methods: A qualitative study to design an MDS for the COVID-19 registry system was performed in five phases at Ahvaz University of Medical Sciences in Khuzestan Province in southwestern Iran, 2020-2021. In the first phase, assessing the information requirements was performed for the COVID-19 registry system. Data elements were identified in the second phase. In the third phase, the MDS was selected, and in the four phases, the COVID-19 registry system was implemented as a pilot study to test the MDS. Finally, based on the experiences gained from the COVID-19 registry system implementation, the MDS were evaluated, and corrections were made., Results: MDS of the COVID-19 registry system contains eight top groups including administrative (34 data elements), disease exposure (61 data elements), medical history and physical examination (138 data elements), findings of clinical diagnostic tests (101 data elements), disease progress and outcome of treatment (55 data elements), medical diagnosis and cause of death (12 data elements), follow-up (14 data elements), and COVID-19 vaccination (19 data elements) data, respectively., Conclusion: Creating a standard and comprehensive MDS can help to design any national data dictionary for COVID-19 and improve the quality of COVID-19 data., (© 2021. The Author(s).)

Background: Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses., Objectives: The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury., Methods: Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey's post hoc test. A p-value <0.05 was considered significant., Results: NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury., Conclusions: The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.

Introduction: Ischemic stroke is one of the leading causes of morbidity and mortality worldwide. Neuroprotective strategies were reported to attenuate cognitive deficits after ischemic incidents. Here we studied the neuroprotective potential of chrysin in a rat model of cerebral Ischemia/Reperfusion (I/R) in the presence or absence of Estrogen Receptors (ERs)., Methods: Adult male Wistar rats were pretreated with chrysin (CH) (CH; 30 mg/kg; gavage; for 21 consecutive days) alone or with selective ERs antagonists (ERα antagonist MPP; ERβ antagonist PHTPP; IP) or nonselective ERs antagonist (ICI182780; IP). Then, the bilateral common carotid arteries were occluded for 20 min, which was followed by 72 h reperfusion. Subsequently, cognitive performance was evaluated by Morris Water Maze (MWM) and shuttle box tasks, and afterward, their hippocampi were removed for ELISA assays and H&E staining. Oxidative indicators Malondialdehyde (MDA) and Glutathione Peroxidase (GPx), as well as inflammation mediators interleukin (IL)-1β and tumor necrosis factor-alpha (TNFα), were measured using commercial kits., Results: Results of the current study showed that the anti-oxidative and anti-inflammatory properties of CH are possible mechanisms that could improve cognitive deficits and prevent neuronal cell death following I/R (P<0.001). These effects were reversed by ICI182780 (P>0.05). Furthermore, when chrysin was co-treated with ERβ antagonist, PHTPP showed a weak neuroprotective effect in I/R rats. However, these parameters were not significantly different when chrysin was combined with ERα antagonist MPP., Conclusion: Our data confirm that chrysin could potentially serve as a neuroprotective agent against devastating effects of cerebral I/R injury, which may be mediated via its interaction with ERs, especially ERβ., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2021 Iranian Neuroscience Society.)

Background and Purpose: Hyperglycemia induced oxidative stress and inflammation lead to development of diabetic cardiomyopathy. Diabetic patients are more at risk for myocardial infarction than non-diabetics. The current study has investigated the involvement of PPARγ activation in effects of crocin as a natural carotenoid against cardiac infarction in diabetic rats., Materials and Methods: Diabetes was induced in male Wistar rats by streptozotocin injection (55 mg/kg, i.p) 15 min after the administration of nicotinamide (110 mg/kg). Then saline, crocin (40 mg/kg, orally) and GW9662 (1 mg/kg, as PPARγ antagonist) were injected for 4 weeks. Isoprenaline was administrated on the 27th and 28th days to induce infarction. Cardiac injury markers, antioxidant enzymes content, blood glucose level, lipid profile, pro and anti-inflammatory cytokines, and PPARγ gene expression were measured., Results: GSH, CAT content, CK-MB isoenzyme, LDH level, IL-10 and PPARγ gene expression in myocardial tissue were decreased in diabetic rats receiving isoprenaline and inflammatory cytokines TNFα and IL-6 and also plasma lipids were increased. Crocin administration significantly ameliorated inflammatory cytokines levels, CK-MB, and LDH contents and also it could enhance antioxidant capacity and PPARγ expression. However, GW9662 administration reversed the effects of crocin., Conclusion: Overexpression of PPARγ in crocin treated rats and inhibition of crocin effects by GW9662 reflected the potential involvement of PPARγ pathway in the protective effects of crocin., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© Springer Nature Switzerland AG 2020.)

Objectives: Cardiovascular disease has an important role in mortality caused by lung injury. Emphysema is associated with impaired pulmonary gas exchange efficiency and airflow limitation associated with small airway inflammation. The aim was to evaluate the interactions between lung injury, inflammation, and cardiovascular disease. Since gallic acid has antioxidant and anti-inflammatory effects, we hypothesized that gallic acid protects the lung and the related heart dysfunction in elastase-induced lung injury., Materials and Methods: Forty-eight Sprague-Dawley male rats were randomly divided into six groups: Control, Porcine pancreatic elastase (PPE) , PPE+GA, and 3 groups for different doses of gallic acid (GA 7.5, GA 15, GA 30 mg/kg). PPE was injected intra-tracheally on days 1 and 10 of the test. In each group, electrocardiography, hemodynamic parameters, oxidative stress, and bronchoalveolar lavage fluid were examined., Results: PPE administration showed a decrease in HR and QRS voltage of electrocardiogram parameters, as well as in hemodynamic parameters ( P <0.05, P <0.01, and P <0.001) and superoxide dismutase (SOD) ( P <0.05). Tumor Necrosis Factor α (TNF-α) ( P <0.001), interleukin 6 (IL-6) ( P <0.001), interleukin 6 (MDA) ( P <0.001), and the total number of white blood cells ( P <0.001) showed an increase in PPE groups. Gallic acid preserved the values of hemodynamic properties, oxidative stress, inflammation, and electrocardiogram parameters in comparison to the PPE group., Conclusion: Briefly, this study showed the valuable effect of gallic acid in cardiac dysfunction related to elastase-induced lung injury. These findings suggested that gallic acid, as a natural antioxidant, has a potential therapeutic effect on preventing oxidative stress, inflammation, and subsequent cardiovascular disease.

Intermittent fasting (IF) is an intervention that can be beneficial for health span and mitigate the risk of developing age-related cardiovascular diseases; however, the involved mechanisms are not well understood. The present study investigated the effects of IF regimens on the plasma level of angiotensin II (Ang II), and the expression of Ang II receptors (AT1aR and AT2R) and angiotensin-converting enzyme 2 (ACE2) in the heart and aorta of male, 3-, 12-, and 24-month-old Wistar rats fed ad libitum (AL), fed ad libitum and fasted 1 day per week (FW), or fasted every other day (EOD) for 3 months. Aging was associated with high circulating levels of Ang II, high level of AT1aR protein expression in the heart and aorta, and low level of AT2R protein expression in the heart and aorta. Both FW and EOD decreased Ang II levels ( p  < 0.01, p  < 0.001) and AT1aR protein expression in the heart ( p  < 0.01, p  < 0.001) and aorta ( p  < 0.001) of old rats. Both FW and EOD increased the expression of AT2R protein in the heart ( p  < 0.05 and p  < 0.001, respectively). However, only EOD increased the expression of AT2R protein ( p  < 0.05) in the aorta. In the old group, both the FW and EOD regimens induced a significant increase in the expression of ACE2 protein in the heart ( p  < 0.01, p  < 0.001 vs. age-matched AL group, respectively). The results suggest that a part of the recovery effect of fasting on cardiovascular system in old rats is mediated through restoration of the balance of renin-angiotensin system.

Intermittent fasting can be effective in reducing metabolic disorders and age-related diseases. However, there remain questions about the effects of fasting with respect to the age in which fasting begins, the fasting models, and the mechanisms involved. We investigated the effects of age of beginning fasting and chronic mild and severe fasting models on blood pressure (BP), insulin/glucose profile, and expression of klotho, sirtuin1 (SIRT1), and sirtuin3 (SIRT3) in male Wistar rats. Young (3 months), middle-aged (12 months), and old (22 months) animals were randomly divided into three subgroups and fed as ad libitum (AL), AL with fasting 1 day per week (FW), and AL with fasting every other day (EOD), respectively, for 3 months. The FW reduced the weight gain in young animals ( p  < 0.001 vs. AL), whereas EOD induced weight loss in all three age categories ( p  < 0.001). Aging was associated with high BP, high glucose, and insulin levels. Both FW and EOD feedings decreased BP and blood glucose level ( p  < 0.001) and EOD decreased insulin level ( p  < 0.05 vs. AL) in old animals. Parallel to aging, the expression of SIRT1 and klotho significantly decreased in plasma and EOD feeding recovered this defect. Both FW and EOD feedings increased the expression of SIRT3 in middle-aged and old rats. Age is a determining factor for the effectiveness of fasting and old animals respond more desirably to fasting. The effect of EOD fasting is more effective than FW fasting in improving the metabolic factors, partly through the recovery of SIRT1 and klotho.

Trimetazidine (TMZ) improves endothelial dysfunction. However, its beneficial effect on endothelial miRNAs is unexplored in diabetes. The aim of the present study was to evaluate the effects of TMZ on plasma miRNA-24 and miRNA-126, dyslipidemia, inflammation, and blood pressure in the diabetic rats. Adult male Sprague-Dawley rats were randomly assigned into four groups (250 ± 20 g, n = 8): a control (C), an untreated diabetic (D), a diabetic group administrated with TMZ at 10 mg/kg (T10), and a diabetic group administrated with TMZ at 30 mg/kg (T30) for eight weeks. Diabetes was induced by injection of alloxan (120 mg/kg). The plasma levels of miR-24, miR-126, lipid profile, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), blood glucose, body weight and systolic blood pressure were measured. The diabetic rats showed decreased plasma miR-24, HDL-c ( P < 0.05), miR-126 ( P < 0.01), body weight changes percent, body weight, and systolic blood pressure ( P < 0.001) and increased triglycerides (TG), VLDL-c ( P < 0.05), TNF-α, total cholesterol (TC) ( P < 0.01) glucose, MDA and IL-6 ( P < 0.001). Interestingly, all these changes were significantly improved by TMZ treatment. Our findings propose that TMZ has protective effects on decreased plasma miR-24 and miR-126 levels, inflammation, dyslipidemia and hypotension, and it may participate in endothelial dysfunction and atherosclerosis.

Chronic obstructive pulmonary disease (COPD) is one of the most important factors in the progress of cardiovascular disease (CVD) which is associated with limited airflow and alveolar demolition. The aim of this study is to investigate the possible protective effect of ellagic acid (EA), as a natural anti-oxidant, against pulmonary arterial hypertension (PAH) and development of lung and heart injuries induced by elastase. Sixty healthy male Sprague-Dawley rats (150-180 g) were divided into six groups: control (saline 0.9%, 1 ml/kg, by gavage), porcine pancreatic elastase (PPE) (25 UI/kg, intratracheal), EA (10, 15, and 30 mg/kg, gavage), PPE + EA (30 mg/kg, by gavage). Lead II electrocardiogram was used to evaluate the inotropic and chronotropic parameters of rat heart using Bio-Amp device and the LabChart software. The anti-oxidant levels (superoxide dismutase, catalase, and glutathione) and malondialdehyde were measured by appropriate kits, and right ventricular systolic pressure (RVSP) was recorded by the PowerLab system and measured by the LabChart software (ADInstruments). Elastase administration caused an increase in RVSP which was in line with elevated inflammatory cells and cytokines, as well as lipid peroxidation, and decreased anti-oxidant levels. Also, electrocardiogram parameters significantly changed in elastase group compared with control rats. Co-treatment with EA not only restored elastase-depleted anti-oxidant levels and prevented pulmonary arterial hypertension but also improved cardiac chronotropic and inotropic properties. Our results documented that elastase administration leads to pulmonary arterial hypertension and EA, as an anti-inflammatory and anti-oxidant factor, can protect development of lung and heart injuries induced by elastase.