scholarly journals Preventive Efficacy of an Antioxidant Compound on Blood Retinal Barrier Breakdown and Visual Dysfunction in Streptozotocin-Induced Diabetic Rats

2022 ◽  
Vol 12 ◽  
Author(s):  
Alessio Canovai ◽  
Rosario Amato ◽  
Alberto Melecchi ◽  
Massimo Dal Monte ◽  
Dario Rusciano ◽  
...  

In diabetic retinopathy (DR), high blood glucose drives chronic oxidative stress and inflammation that trigger alterations of the neurovascular balance finally resulting in vascular abnormalities and retinal cell death, which converge towards altered electroretinogram (ERG). In the last years, a growing body of preclinical evidence has suggested that nutrients with anti-inflammatory/antioxidant properties can be able to hamper DR progression since its very early stages. In the present study, we used a streptozotocin-induced rat model of DR, which mimics most aspects of the early stages of human DR, to test the preventive efficacy of a novel compound containing cyanidin-3-glucoside (C3G), verbascoside and zinc as nutrients with antioxidant and anti-inflammatory properties. Western blot, immunofluorescence and electroretinographic analyses demonstrated a dose-dependent inhibition of oxidative stress- and inflammation-related mechanisms, with a significant counterpart in preventing molecular mechanisms leading to DR-associated vasculopathy and its related retinal damage. Preventive efficacy of the compound on dysfunctional a- and b-waves was also demonstrated by electroretinography. The present demonstration that natural compounds, possibly as a consequence of vascular rescue following ameliorated oxidative stress and inflammation, may prevent the apoptotic cascade leading to ERG dysfunction, adds further relevance to the potential application of antioxidants as a preventive therapy to counteract DR progression.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yves Wang ◽  
Nhu Nguyen ◽  
Keith Nehrke ◽  
Paul S Brookes ◽  
Thu H Le

The glutathione S-transferase ( Gst ) gene family encodes antioxidant enzymes. In humans, a common null allele deletion variant of GST μ-1 ( GSTM1 ) is highly prevalent across populations and is associated with increased risk and progression of various diseases. Using a Gstm1 knockout (KO) mouse model, we previously showed that KO mice with angiotensin II-induced hypertension (HTN) have increased kidney injury compared to wild-type (WT) controls, mediated by elevated oxidative stress. In the same mouse model, we have recently reported that in a Langendorff-perfused cardiac ischemia-reperfusion injury (IRI) model, where damage is also mediated by oxidative stress, male KO hearts are protected while females are not. Here, we investigated the molecular mechanisms for this difference in male hearts. WT and KO mice of both sexes were studied at 12-20 weeks of age. Hearts were snap frozen at baseline and after 25 min of global ischemia, and kidneys were collected at baseline and 4 weeks following HTN induction. A panel of 18 Gst genes were probed by qPCR from baseline hearts and kidneys of both sexes. Global metabolites were assayed using Metabolon, Inc. from hearts of both sexes and kidneys of males, at both baseline and diseased states. Analysis by qPCR (n = 3/group) showed that male, but not female, KO hearts had upregulation of other Gst s. In contrast, no significant differences between were found in male kidneys. Metabolomics (n = 6/group) detected 695 metabolites in hearts and 926 in kidneys. There were increases in several metabolites in KO vs. WT hearts including those with antioxidant properties. Notably, increases in carnosine and anserine were observed in KO male hearts but not in female hearts, while that of other antioxidant-related metabolites were observed in hearts of both sexes, but not in kidneys. HTN induced significant increases in metabolites in KO vs. WT kidneys in the pathways related to and linking methionine, cysteine, and glutathione, which were not observed in hearts. In this study, gene expression and metabolites suggest that the mechanisms compensating for the loss of GSTM1 are both tissue and sex specific. The resulting differences in antioxidant enzymes and metabolites may explain the unexpected protection for male Gstm1 KO hearts in IRI.


Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 306 ◽  
Author(s):  
Francesca Oppedisano ◽  
Roberta Macrì ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Cristina Carresi ◽  
...  

Polyunsaturated fatty acids (n-3 PUFAs) are long-chain polyunsaturated fatty acids with 18, 20 or 22 carbon atoms, which have been found able to counteract cardiovascular diseases. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in particular, have been found to produce both vaso- and cardio-protective response via modulation of membrane phospholipids thereby improving cardiac mitochondrial functions and energy production. However, antioxidant properties of n-3 PUFAs, along with their anti-inflammatory effect in both blood vessels and cardiac cells, seem to exert beneficial effects in cardiovascular impairment. In fact, dietary supplementation with n-3 PUFAs has been demonstrated to reduce oxidative stress-related mitochondrial dysfunction and endothelial cell apoptosis, an effect occurring via an increased activity of endogenous antioxidant enzymes. On the other hand, n-3 PUFAs have been shown to counteract the release of pro-inflammatory cytokines in both vascular tissues and in the myocardium, thereby restoring vascular reactivity and myocardial performance. Here we summarize the molecular mechanisms underlying the anti-oxidant and anti-inflammatory effect of n-3 PUFAs in vascular and cardiac tissues and their implication in the prevention and treatment of cardiovascular disease.


Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 985 ◽  
Author(s):  
Abdelhafid Nani ◽  
Babar Murtaza ◽  
Amira Sayed Khan ◽  
Naim Akhtar Khan ◽  
Aziz Hichami

Nutrition transition can be defined as shifts in food habits, and it is characterized by high-fat (chiefly saturated animal fat), hypercaloric and salty food consumption at the expense of dietary fibers, minerals and vitamins. Western dietary patterns serve as a model for studying the impact of nutrition transition on civilization diseases, such as obesity, which is commonly associated with oxidative stress and inflammation. In fact, reactive oxygen species (ROS) overproduction can be associated with nuclear factor-κB (NF-κB)-mediated inflammation in obesity. NF-κB regulates gene expression of several oxidant-responsive adipokines including tumor necrosis factor-α (TNF-α). Moreover, AMP-activated protein kinase (AMPK), which plays a pivotal role in energy homeostasis and in modulation of metabolic inflammation, can be downregulated by IκB kinase (IKK)-dependent TNF-α activation. On the other hand, adherence to a Mediterranean-style diet is highly encouraged because of its healthy dietary pattern, which includes antioxidant nutraceuticals such as polyphenols. Indeed, hydroxycinnamic derivatives, quercetin, resveratrol, oleuropein and hydroxytyrosol, which are well known for their antioxidant and anti-inflammatory activities, exert anti-obesity proprieties. In this review, we highlight the impact of the most common polyphenols from Mediterranean foods on molecular mechanisms that mediate obesity-related oxidative stress and inflammation. Hence, we discuss the effects of these polyphenols on a number of signaling pathways. We note that Mediterranean diet (MedDiet) dietary polyphenols can de-regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and NF-κB-mediated oxidative stress, and metabolic inflammation. MedDiet polyphenols are also effective in upregulating downstream effectors of several proteins, chiefly AMPK.


2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Rahima Begum ◽  
Saurav Howlader ◽  
A. N. M. Mamun-Or-Rashid ◽  
S. M. Rafiquzzaman ◽  
Ghulam Md Ashraf ◽  
...  

The biological and therapeutic properties of seaweeds have already been well known. Several studies showed that among the various natural marine sources of antioxidants, seaweeds have become a potential source of antioxidants because of their bioactive compounds. Most of the metabolic diseases are caused by oxidative stress. It is very well known that antioxidants have a pivotal role in the treatment of those diseases. Recent researches have revealed the potential activity of seaweeds as complementary medicine, which have therapeutic properties for health and disease management. Among the seaweeds, brown seaweeds (Phaeophyta) and their derived bioactive substances showed excellent antioxidant properties than other seaweeds. This review focuses on brown seaweeds and their derived major bioactive compounds such as sulfated polysaccharide, polyphenol, carotenoid, and sterol antioxidant effects and molecular mechanisms in the case of the oxidative stress-originated disease. Antioxidants have a potential role in the modification of stress-induced signaling pathways along with the activation of the oxidative defensive pathways. This review would help to provide the basis for further studies to researchers on the potential antioxidant role in the field of medical health care and future drug development.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rosario Amato ◽  
Maria Grazia Rossino ◽  
Maurizio Cammalleri ◽  
Anna Maria Timperio ◽  
Giuseppina Fanelli ◽  
...  

Lisosan G (LG), a fermented powder obtained from whole grains, is a nutritional supplement containing a variety of metabolites with documented antioxidant properties. We have recently demonstrated that orally administered LG protects diabetic rodent retinas from oxidative stress, inflammation, apoptosis, blood-retinal barrier disruption, and functional damage. Here, we investigated whether LG may exert protective effects in a model of glaucoma and measured the amounts of selected LG components that reach the retina after oral LG administration. Six-month-old DBA/2J mice were given an aqueous LG solution in place of drinking water for 2 mo. During the 2 mo of treatment with LG, the intraocular pressure (IOP) was monitored and the retinal ganglion cell (RGC) functional activity was recorded with pattern-electroretinography (PERG). At the end of the 2-mo period, the expression of oxidative stress and inflammatory markers was measured with qPCR, and RGC survival or macroglial activation were assessed with immunofluorescence. Alternatively, LG was administered by gavage and the concentrations of four of the main LG components (nicotinamide, gallic acid, 4-hydroxybenzoic acid, and quercetin) were measured in the retinas in the following 24 h using mass spectrometry. LG treatment in DBA/2J mice did not influence IOP, but it affected RGC function since PERG amplitude was increased and PERG latency was decreased with respect to untreated DBA/2J mice. This improvement of RGC function was concomitant with a significant decrease of both oxidative stress and inflammation marker expression, of RGC loss, and of macroglial activation. All four LG metabolites were found in the retina, although with different proportions with respect to the amount in the dose of administered LG, and with different temporal profiles in the 24 h following administration. These findings are consistent with neuroenhancing and neuroprotective effects of LG in glaucoma that are likely to derive from its powerful antioxidant properties. The co-occurrence of different metabolites in LG may provide an added value to their beneficial effects and indicate LG as a basis for the potential treatment of a variety of retinal pathologies.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Sooriya Arachchige Sachini Jayawardana ◽  
Jayanetti Koralalage Ramani Radhika Samarasekera ◽  
Gardhi Hettiarachchige Chamari Madhu Hettiarachchi ◽  
Jaanaki Gooneratne ◽  
Muhammad Iqbal Choudhary ◽  
...  

The prevalence of inflammatory-mediated and oxidative stress-associated diseases is increasing worldwide, creating an increasing demand for novel sources of anti-inflammatory agents and antioxidants. This study was focused on determining the in vitro arachidonate 5-lipoxygenase (A5-LOX), xanthine oxidase (XO), hyaluronidase and oxidative burst inhibitory activities, and antioxidant properties of Ravi, Rawana, and Oshadha finger millet varieties using ethanolic and methanolic extracts. Among all extracts, the methanolic extract of Oshadha exhibited the highest A5-LOX (IC50 value: 484.42 μg/ml) and XO (IC50 value: 764.34 μg/ml) inhibitory activities. All extracts showed less than 50% hyaluronidase inhibitory activity at 1 mg/ml concentration. Methanolic extracts showed moderate inhibitory potential on reactive oxygen species (ROS) generated from whole blood phagocytes, with IC50 values ranging between 26.9 and 27.7 μg/ml, when compared to ibuprofen (IC50 value: 11.18 μg/ml). All extracts showed potent inhibition of ROS produced from polymorphonuclear neutrophils isolated from human blood when compared to ibuprofen (IC50 value: 2.47 μg/ml) and IC50 values of methanolic and ethanolic extracts ranged from 0.29 to 0.47 μg/ml and 1.35 to 1.70 μg/ml, respectively. All extracts had significantly high amounts of phenolic compounds including flavonoids and the potential to scavenge 2,2 ′ -azino-bis (3-ethylbenzothiazoline-6-sulfonic) acid (ABTS) cation, 2,2-diphenyl-1-picryl-hydrazyl (DPPH), and oxygen radicals. Besides, they were able to reduce metal ions and chelate metal ions terminating radical generating reactions. This is the first report of A5-LOX, XO, hyaluronidase, and oxidative burst inhibitory properties of any extract of any finger millet variety cultivated in Sri Lanka. The findings revealed the potential of using these finger millet extracts as natural sources of anti-inflammatory drug candidates. Additionally, the findings indicated that Ravi, Rawana, and Oshadha varieties are good sources of antioxidants. Therefore, consumption of these finger millet varieties on a regular basis may play an important role in the prevention and dietary management of oxidative stress-associated diseases.


Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 192 ◽  
Author(s):  
Thu Hang Nguyen ◽  
Hong Diep Le ◽  
Thanh Nguyen Thi Kim ◽  
Hai Pham The ◽  
Thi Mai Nguyen ◽  
...  

Oxidative stress and inflammation are commonly present in many chronic diseases. These responses are closely related to pathophysiological processes. The inflammatory process can induce oxidative stress and vice versa through the activation of multiple pathways. Therefore, agents with antioxidant and/or anti-inflammatory activities are very useful in the treatment of many pathologies. Clerodendrum cyrthophyllum Turcz, a plant belonging to the Verbenaceae family, is used in Vietnamese traditional medicine for treating migraine, hypertension, inflammation of the throat, and rheumatic arthritis. Despite its usefulness, studies on its biological properties are still scarce. In this study, ethanol extract (EE) of leaves of C. cyrtophyllum showed protective activity against CuSO4 toxicity. The protective activity was proven to relate to antioxidant and anti-inflammatory properties. EE exhibited relatively high antioxidant activity (IC50 of 16.45 µg/mL) as measured by DPPH assay. In an in vivo anti-antioxidant test, three days post fertilization (dpf) zebrafish larvae were treated with different concentrations of EE for 1 h and then exposed to 10 µM CuSO4 for 20 min to induce oxidative stress. Fluorescent probes were used to detect and quantify oxidative stress by measuring the fluorescent intensity (FI) in larvae. FI significantly decreased in the presence of EE at 5 and 20 µg/mL, demonstrating EE’s profound antioxidant effects, reducing or preventing oxidative stress from CuSO4. Moreover, the co-administration of EE also protected zebrafish larvae against oxidative damage from CuSO4 through down-regulation of hsp70 and gadd45bb expression and upregulation of sod. Due to copper accumulation in zebrafish tissues, the damage and oxidative stress were exacerbated overtime, resulting in the upregulation of genes related to inflammatory processes such as cox-2, pla2, c3a, mpo, and pro- and anti-inflammatory cytokines (il-1ß, il-8, tnf-α, and il-10, respectively). However, the association of CuSO4 with EE significantly decreased the expression of cox-2, pla2, c3a, mpo, il-8, and il-1ß. Taken together, the results suggest that EE has potent antioxidant and anti-inflammatory activities and may be useful in the treatment of various inflammatory diseases.


Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 950
Author(s):  
Martial Caillaud ◽  
Yu Aung Myo ◽  
Bryan McKiver ◽  
Urszula Osinska Warncke ◽  
Danielle Thompson ◽  
...  

Peripheral neuropathies (PN) can be triggered after metabolic diseases, traumatic peripheral nerve injury, genetic mutations, toxic substances, and/or inflammation. PN is a major clinical problem, affecting many patients and with few effective therapeutics. Recently, interest in natural dietary compounds, such as polyphenols, in human health has led to a great deal of research, especially in PN. Curcumin is a polyphenol extracted from the root of Curcuma longa. This molecule has long been used in Asian medicine for its anti-inflammatory, antibacterial, and antioxidant properties. However, like numerous polyphenols, curcumin has a very low bioavailability and a very fast metabolism. This review addresses multiple aspects of curcumin in PN, including bioavailability issues, new formulations, observations in animal behavioral tests, electrophysiological, histological, and molecular aspects, and clinical trials published to date. The, review covers in vitro and in vivo studies, with a special focus on the molecular mechanisms of curcumin (anti-inflammatory, antioxidant, anti-endoplasmic reticulum stress (anti-ER-stress), neuroprotection, and glial protection). This review provides for the first time an overview of curcumin in the treatment of PN. Finally, because PN are associated with numerous pathologies (e.g., cancers, diabetes, addiction, inflammatory disease...), this review is likely to interest a large audience.


2019 ◽  
Vol 21 (1) ◽  
pp. 263 ◽  
Author(s):  
Shara Francesca Rapa ◽  
Biagio Raffaele Di Iorio ◽  
Pietro Campiglia ◽  
August Heidland ◽  
Stefania Marzocco

Chronic kidney disease (CKD) is a debilitating pathology with various causal factors, culminating in end stage renal disease (ESRD) requiring dialysis or kidney transplantation. The progression of CKD is closely associated with systemic inflammation and oxidative stress, which are responsible for the manifestation of numerous complications such as malnutrition, atherosclerosis, coronary artery calcification, heart failure, anemia and mineral and bone disorders, as well as enhanced cardiovascular mortality. In addition to conventional therapy with anti-inflammatory and antioxidative agents, growing evidence has indicated that certain minerals, vitamins and plant-derived metabolites exhibit beneficial effects in these disturbances. In the current work, we review the anti-inflammatory and antioxidant properties of various agents which could be of potential benefit in CKD/ESRD. However, the related studies were limited due to small sample sizes and short-term follow-up in many trials. Therefore, studies of several anti-inflammatory and antioxidant agents with long-term follow-ups are necessary.


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