Depletion Of Endogenous Antioxidants Research Articles

Berberine mitigates acetamiprid-induced hepatotoxicity and inflammation via regulating endogenous antioxidants and NF-κB/TNF-α signaling in rats.

Acetamiprid is a neonicotinoid insecticide used on a large scale and has been reported for oxidative stress-mediated toxicity and physiological alterations in mammals. The plant-derived natural antioxidant berberine (BBR) possesses protective potential against inflammation, structural changes, and cellular toxicity. The current study aimed to investigate the toxic effects of acetamiprid exposure and the antioxidative and anti-inflammatory efficacy of BBR in rat liver tissue. The results showed that intragastric exposure of acetamiprid (21.7mg/kg b.wt, i.e., 1/10 of LD50) for 21days significantly elicited oxidative stress as evidenced by lipid peroxidation, protein oxidation, and depletion of endogenous antioxidants. Furthermore, acetamiprid exposure elevated NF-κB, TNF-α, IL-1β, IL-6, and IL-12 expression and caused structural alterations in liver tissue. Biochemical results showed that 2-h pre-treatment of BBR (150mg/kg b.wt; 21days) reduced damage to lipids and proteins, replenished GSH, enhanced SOD and catalase activities, and offered antioxidative effects against acetamiprid toxicity. Also, BBR suppressed inflammation by regulating NF-κB/TNF-α signaling in hepatic tissue of acetamiprid-intoxicated rats. Histopathological examination confirmed the hepatoprotective effects of BBR. Our findings indicate that BBR might be a potential ameliorative agent against oxidative stress-mediated hepatotoxicity.

Tannic Acid Mitigates Rotenone-Induced Dopaminergic Neurodegeneration by Inhibiting Inflammation, Oxidative Stress, Apoptosis, and Glutamate Toxicity in Rats.

Parkinson's disease (PD), a movement disorder, is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the brain. The etiopathogenesis of PD involves increased oxidative stress, augmented inflammation, impaired autophagy, accumulation of α-synuclein, and α-Glutamate neurotoxicity. The treatment of PD is limited and there is a lack of agents to prevent the disease/delay its progression and inhibit the onset of pathogenic events. Many agents of natural and synthetic origin have been investigated employing experimental models of PD, mimicking human PD. In the present study, we assessed the effect of tannic acid (TA) in a rodent model of PD induced by rotenone (ROT), a pesticide and an environmental toxin of natural origin reported to cause PD in agricultural workers and farmers. Rotenone (2.5 mg/kg/day, i.p.) was administered for 28 days, and TA (50 mg/kg, orally) was administered 30 min before ROT injections. The study results showed an increase in oxidative stress, as evidenced by the depletion of endogenous antioxidants and enhanced formation of lipid peroxidation products, along with the onset of inflammation following a rise in inflammatory mediators and proinflammatory cytokines. ROT injections have also augmented apoptosis, impaired autophagy, promoted synaptic loss, and perturbed α-Glutamate hyperpolarization in rats. ROT injections also induced the loss of dopaminergic neurons subsequent to the activation of microglia and astrocytes. However, TA treatment was observed to reduce lipid peroxidation, prevent loss of endogenous antioxidants, and inhibit the release and synthesis of proinflammatory cytokines, in addition to the favorable modulation of apoptosis and autophagic pathways. Treatment with TA also attenuated the activation of microglia and astrocytes along with preservation of dopaminergic neurons following reduced loss of dopaminergic neurodegeneration and inhibition of synaptic loss and α-Glutamate cytotoxicity. The effects of TA in ROT-induced PD were attributed to the antioxidant, anti-inflammatory, antiapoptotic, and neurogenesis properties. Based on the present study findings, it can be concluded that TA may be a promising novel therapeutic candidate for pharmaceutical as well as nutraceutical development owing to its neuroprotective properties in PD. Further regulatory toxicology and translational studies are suggested for future clinical usage in PD.

Hormesis and Oxidative Distress: Pathophysiology of Reactive Oxygen Species and the Open Question of Antioxidant Modulation and Supplementation.

Alterations of redox homeostasis leads to a condition of resilience known as hormesis that is due to the activation of redox-sensitive pathways stimulating cell proliferation, growth, differentiation, and angiogenesis. Instead, supraphysiological production of reactive oxygen species (ROS) exceeds antioxidant defence and leads to oxidative distress. This condition induces damage to biomolecules and is responsible or co-responsible for the onset of several chronic pathologies. Thus, a dietary antioxidant supplementation has been proposed in order to prevent aging, cardiovascular and degenerative diseases as well as carcinogenesis. However, this approach has failed to demonstrate efficacy, often leading to harmful side effects, in particular in patients affected by cancer. In this latter case, an approach based on endogenous antioxidant depletion, leading to ROS overproduction, has shown an interesting potential for enhancing susceptibility of patients to anticancer therapies. Therefore, a deep investigation of molecular pathways involved in redox balance is crucial in order to identify new molecular targets useful for the development of more effective therapeutic approaches. The review herein provides an overview of the pathophysiological role of ROS and focuses the attention on positive and negative aspects of antioxidant modulation with the intent to find new insights for a successful clinical application.

Delineation of Neuroprotective Effects and Possible Benefits of AntioxidantsTherapy for the Treatment of Alzheimer’s Diseases by Targeting Mitochondrial-Derived Reactive Oxygen Species: Bench to Bedside

Alzheimer's disease (AD) is considered the sixth leading cause of death in elderly patients and is characterized by progressive neuronal degeneration and impairment in memory, language, etc. AD is characterized by the deposition of senile plaque, accumulation of fibrils, and neurofibrillary tangles (NFTs) which are responsible for neuronal degeneration. Amyloid-β (Aβ) plays a key role in the process of neuronal degeneration in the case of AD. It has been reported that Aβ is responsible for the production of reactive oxygen species (ROS), depletion of endogenous antioxidants, increase in intracellular Ca2+ which further increases mitochondria dysfunctions, oxidative stress, release of pro-apoptotic factors, neuronal apoptosis, etc. Thus, oxidative stress plays a key role in the pathogenesis of AD. Antioxidants are compounds that have the ability to counteract the oxidative damage conferred by ROS. Therefore, the antioxidant therapy may provide benefits and halt the progress of AD to advance stages by counteracting neuronal degeneration. However, despite the beneficial effects imposed by the antioxidants, the findings from the clinical studies suggested inconsistent results which might be due to poor study design, selection of the wrong antioxidant, inability of the molecule to cross the blood-brain barrier (BBB), treatment in the advanced state of disease, etc. The present review insights into the neuroprotective effects and limitations of the antioxidant therapy for the treatment of AD by targeting mitochondrial-derived ROS. This particular article will certainly help the researchers to search new avenues for the treatment of AD by utilizing mitochondrial-derived ROS-targeted antioxidant therapies.

A Systematic Review of Carotenoids in the Management of Diabetic Retinopathy.

Diabetic retinopathy, which was primarily regarded as a microvascular disease, is the leading cause of irreversible blindness worldwide. With obesity at epidemic proportions, diabetes-related ocular problems are exponentially increasing in the developed world. Oxidative stress due to hyperglycemic states and its associated inflammation is one of the pathological mechanisms which leads to depletion of endogenous antioxidants in retina in a diabetic patient. This contributes to a cascade of events that finally leads to retinal neurodegeneration and irreversible vision loss. The xanthophylls lutein and zeaxanthin are known to promote retinal health, improve visual function in retinal diseases such as age-related macular degeneration that has oxidative damage central in its etiopathogenesis. Thus, it can be hypothesized that dietary supplements with xanthophylls that are potent antioxidants may regenerate the compromised antioxidant capacity as a consequence of the diabetic state, therefore ultimately promoting retinal health and visual improvement. We performed a comprehensive literature review of the National Library of Medicine and Web of Science databases, resulting in 341 publications meeting search criteria, of which, 18 were found eligible for inclusion in this review. Lutein and zeaxanthin demonstrated significant protection against capillary cell degeneration and hyperglycemia-induced changes in retinal vasculature. Observational studies indicate that depletion of xanthophyll carotenoids in the macula may represent a novel feature of DR, specifically in patients with type 2 or poorly managed type 1 diabetes. Meanwhile, early interventional trials with dietary carotenoid supplementation show promise in improving their levels in serum and macular pigments concomitant with benefits in visual performance. These findings provide a strong molecular basis and a line of evidence that suggests carotenoid vitamin therapy may offer enhanced neuroprotective effects with therapeutic potential to function as an adjunct nutraceutical strategy for management of diabetic retinopathy.

The postoperative redox status of patients with diabetes mellitus: a mini review.

The human organism is exposed to variable endogenous and exogenous factors that result in the induction of free radicals. Surgeries are associated with increased inflammation and production of free radicals through various mechanisms, including ischemia, hemolysis, or endogenous antioxidant depletion. Importantly, a more oxidized redox status could lead to the condition known as "oxidative stress," which is related to alterations in insulin signaling and may lead to insulin resistance and diabetes mellitus. Therefore, patients with diabetes who undergo surgery could be more vulnerable compared with healthy individuals. Thus, this review focuses on the currently available literature regarding the link between the redox status and diabetes complications after surgery and the methods used to assess the redox status of patients, which is the first step to designing an appropriate treatment strategy. To this end, we queried PubMed for novel works published up to May 2020.

Effect of low-dose X-rays on the liver of whole-body irradiated rats

Purpose: To investigate the effect of whole-body low-dose radiation (10 cGy of 6 MV x-rays) given prior to a challenging dose of 2 Gy x-rays on adaptive response in the liver of ratsMaterial and methods: Rats were either irradiated with 10 cGy, 2 Gy or 10 cGy 24 h prior to 2 Gy (10 cGy–2 Gy irradiated). Liver samples were analyzed for apoptosis, caspase-3, Bcl-2, by flow cytometry. DNA damage was determined by alkaline comet assay. The protein damage, lipid damage, and expression of endogenous antioxidants, Il-1β, Il-6, and TNF-α were determined by ELISA.Results: An increase in apoptosis paralleled with increase in DNA damage and expression of Il-1β, Il-6, and TNF-α, protein oxidation, and lipid peroxidation were detected in all irradiated groups. The irradiated rats with 10 cGy–2 Gy and the 2 Gy-irradiated showed the highest effect. The increase in oxidative damage of protein and lipid was accompanied with depletion of endogenous antioxidants. In all cases, the10 cGy–2 Gy irradiated group showed similar or higher effect than the 2 Gy-irradiated group.Conclusions: Under the present experimental conditions, There is no evidence that 10 cGy-irradiation protected the liver cells against a subsequent higher dose. The significant effect of 10 cGy-irradiation emphasizes the low-dose radiation-associated risk.

Hepatoprotective effects of blue honeysuckle on CCl4-induced acute liver damaged mice.

The objective of this study was to evaluate the hepatoprotective effects of blue honeysuckle (BH) on carbon tetrachloride (CCl4)‐induced acute hepatic damage in mice. The experiment used a total of 60 ICR mice, which were divided into six groups. Except for the intact control groups, all groups received a single intraperitoneal injection of CCl4 after a 7 day pre‐treatment period with distilled water, BH extracts, or silymarin. Twenty‐four hours after the CCl4 injection, the following observations, representative of classical oxidative stress‐mediated centrolobular necrotic acute liver injuries, were observed: decreased body weight; small nodule formation and enlargement on the gross inspections with related liver weight increase; elevation of serum AST and ALT, increases in hepatic lipid peroxidation and related depletion of endogenous antioxidants and antioxidative enzymes; centrolobular necrosis; increases in apoptotic markers, lipid peroxidation markers, and oxidative stress markers. However, liver damage was significantly inhibited by the pre‐treatment with BH extracts. The present study demonstrated that oral administration of BH extracts prior to exposure to CCl4 conferred favorable hepatoprotective effects. These results demonstrated that BHe possessed suitable properties for use as a potent hepatoprotective medicinal food.

Cardioprotective Effect of Ajwa Date Aqueous Extract on Doxorubicin-Induced Toxicity in Rats

Doxorubicin (DOX) is one of the most potent and widely used chemotherapeutic agents to treat several malignancies. However, the clinical use of DOX is seriously restricted due to its acute and chronic cardiotoxic side effects This study investigated the protective effect of (Ajwa) date aqueous extract (AJDAE) against doxorubicin-induced cardiotoxicity in rats. Sixty Wister albino male rats (150-200 gms.) were comprised in our study and divided into six equal groups: group I (untreated control), group II, group III, rats were orally received AJDAE (0.75 & 1.5 gm/ kg.bw) respectively, for 4 weeks, rats of groups IV, V and VI were intraperitoneally injected with one dose of doxorubicin (5 mg/kg.bw) at the end of the 4th week of the study to induce cardiotoxicity, rats of groups V & VI were orally received AJDAE (0.75 & 1.5 gm/ kg.bw) respectively. Cardiac enzymes, lipid profile, SOD, GR, GST, GPx, CAT and MDA in rats’ hearts homogenate, urinary 8OHdG as well as DNA integrity and histopathological changes were investigated in all studied rats.Oral administration of AJDAE (0.75 & 1.5 gm/ kg.bw) attenuated the cardiotoxicity of DOX, improved the cardiac enzymes, lipid profile, reduced the urinary 8OHdG and prohibited the depletion of endogenous antioxidants and suppressed lipid peroxidation (MDA). Moreover, AJDAE enhanced DNA integrity. Histological findings showed that AJDAE (0.75 & 1.5 gm/ kg.bw) administration reduced cardiomyocytes alterations, congestion, edema and the intense cellular stress exerted on myocardial fibers as well as restored the cardiomyocytes architecture. Our data showed that AJDAE obviously resulted in protective effects against DOX-induced cardiotoxicity in rat’s heart. It can be concluded that Ajwa date offers a considerable protection against DOX-induced cardiotoxicity.

Novel Nrf2-Inducer Prevents Mitochondrial Defects and Oxidative Stress in Friedreich's Ataxia Models.

Friedreich’s Ataxia (FRDA) is an autosomal recessive neurodegenerative disorder, affecting dorsal root ganglia (DRG), cerebellar dentate nuclei and heart. It is caused by a GAA repeat expansion mutation within the frataxin gene (FXN). This impedes FXN transcription resulting in a progressive decrease of the mitochondrial protein, frataxin. Increased oxidative stress leading to a chronic depletion of endogenous antioxidants affects the survival of the cells and causes neurodegeneration. In particular, cerebellar granule neurons (CGNs) show a significant increase of reactive oxygen species (ROS), lipid peroxidation and lower level of reduced glutathione (GSH). In FRDA, one of the major pathways of oxidant scavengers, the Nrf2 antioxidant pathway, is defective. Previous studies on FRDA-like CGNs showed that the reduced level of frataxin and the oxidative stress induce mitochondrial impairments. By triggering the Nrf2 endogenous pathway pharmacologically we determined whether this could promote mitochondrial fitness and counteract oxidative stress. In this work, we sought to investigate the beneficial effect of a promising Nrf2-inducer, omaveloxolone (omav), in CGNs from two FRDA mouse models, KIKO and YG8R, and human fibroblasts from patients. We found that CGNs from both KIKO and YG8R presented Complex I deficiency and that omav was able to restore substrate availability and Complex I activity. This was also confirmed in human primary fibroblasts from FRDA patients. Although fibroblasts are not the major tissue affected, we found that they show significant differences recapitulating the disease; this is therefore an important tool to investigate patients’ pathophysiology. Interestingly, we found that patient fibroblasts had an increased level of endogenous lipid peroxidation and mitochondrial ROS (mROS), and lower GSH at rest. Omav was able to reverse this phenotype, protecting the cells against oxidative stress. By stimulating the cells with hydrogen peroxide (H2O2) and looking for potential mitochondrial pathophysiology, we found that fibroblasts could not maintain their mitochondrial membrane potential (ΔΨm). Remarkably, omav was protective to mitochondrial depolarization, promoting mitochondrial respiration and preventing cell death. Our results show that omav promotes Complex I activity and protect cells from oxidative stress. Omav could, therefore, be used as a novel therapeutic drug to ameliorate the pathophysiology of FRDA.

Role of ROS and Nutritional Antioxidants in Human Diseases.

The overproduction of reactive oxygen species (ROS) has been implicated in the development of various chronic and degenerative diseases such as cancer, respiratory, neurodegenerative, and digestive diseases. Under physiological conditions, the concentrations of ROS are subtlety regulated by antioxidants, which can be either generated endogenously or externally supplemented. A combination of antioxidant-deficiency and malnutrition may render individuals more vulnerable to oxidative stress, thereby increasing the risk of cancer occurrence. In addition, antioxidant defense can be overwhelmed during sustained inflammation such as in chronic obstructive pulmonary diseases, inflammatory bowel disease, and neurodegenerative disorders, cardiovascular diseases, and aging. Certain antioxidant vitamins, such as vitamin D, are essential in regulating biochemical pathways that lead to the proper functioning of the organs. Antioxidant supplementation has been shown to attenuate endogenous antioxidant depletion thus alleviating associated oxidative damage in some clinical research. However, some results indicate that antioxidants exert no favorable effects on disease control. Thus, more studies are warranted to investigate the complicated interactions between ROS and different types of antioxidants for restoration of the redox balance under pathologic conditions. This review highlights the potential roles of ROS and nutritional antioxidants in the pathogenesis of several redox imbalance-related diseases and the attenuation of oxidative stress-induced damages.

Nepeta deflersiana attenuates isoproterenol-induced myocardial injuries in rats: Possible involvement of oxidative stress, apoptosis, inflammation through nuclear factor (NF)-κB downregulation

BackgroundNepeta deflersiana (Lamiaceae) is a perennial herb used in the Saudi and Yemeni folk medicine as an anti-inflammatory, carminative, and antirheumatic agent. PurposeThis study explores the phytochemistry of the plant and the cardioprotective effect of N. deflersiana ethanolic extract (NDEE) against isoproterenol (ISP)-induced myocardial injury in rats. Design/MethodsCardiac function, serum cardiac enzymes, myocardial antioxidants, inflammatory, and apoptotic biomarkers, and histopathological parameters were studied in ISP-injured Wistar rat heart tissues. ResultsTo the best of our knowledge, this is the first study to report the isolation of nine secondary metabolites from this plant: 1α-hydroxy-7α,14α,18-triacetoxy-isopimara-8,15-diene (1), β-sitosterol (2), lupeol (3), ursolic acid (4), 2,3-dihydroxy ursolic acid (5), caffeic acid (6), methyl rosmarinate (7), rosmarinic acid (8), and an irridoid glucoside 8-epi-7-deoxyloganic acid (9). To explain the mechanisms underlying the cardioprotective effect of NDEE, we evaluated the redox-sensitivity of NDEE in ISP-induced cardiac injury. The oral administration of NDEE (50 and 100 mg/kg b.w) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH, and NO) and myocyte injury marker enzymes and inhibited lipid peroxidation (MDA, MPO). Moreover, NDEE downregulated the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-10) and apoptotic markers (caspase-3 and Bax) and upregulated the anti-apoptotic protein Bcl2. Furthermore, NDEE pretreatment significantly downregulated cardiac NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity. Histological data showed that NDEE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the architecture of cardiomyocytes. ConclusionNDEE demonstrated strong antioxidant, cardioprotective, anti-inflammatory, and anti-apoptotic potential against myocardial damage. This further endorses the use of N. deflersiana in Yemeni folk medicine against cardiovascular diseases.

‘Ajwa’ dates (Phoenix dactylifera L.) extract ameliorates isoproterenol-induced cardiomyopathy through downregulation of oxidative, inflammatory and apoptotic molecules in rodent model

Background/PurposeAjwa, a special variety of Saudi Arabian dates (Phoenix dactylifera L.) is a rich source of nutrients, fibers and bioactive molecules. While previous studies have shown the therapeutic value of dates phytoconstituents in liver and kidney diseases etc., its cardioprotective potential remains elusive. We therefore, investigated the cardioprotective effect of lyophilized Ajwa extract (AJLE) ex vivo as well as in vivo. MethodsEx vivo cardioprotective effect of AJLE was evaluated on DCFH-toxicated cardiomyoblast cells (H9C2). In vivo hemodynamics, cardiac function, serum cardiac enzymes, myocardial antioxidant, inflammatory and apoptotic biomarkers as well as histopathological parameters were studied in IPS-injured Wistar rat heart tissues. ResultsAJLE (250 µg/ml) attenuated the cytotoxicity and enhanced the H9C2 proliferation by up to 40%. Oral administration of AJLE (250 and 500 mg/kg.bw) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH and NO) and myocyte injury marker enzymes, and inhibited lipid peroxidation (MDA, MPO). Moreover, AJLE downregulated the expressions of proinflammatory cytokines (IL-6, IL-10 and TNFα) and apoptotic markers (caspase-3 and Bax), and upregulated the anti-apototic protein Bcl2. Histological data showed that AJLE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the cardiomyocytes architecture. ConclusionTaken together, our data revealed that AJLE had strong antioxidant, hypolipidimic, cardioprotective, anti-inflammatory and anti-apoptotic potential against myocardial damage. This further endorses the use of Ajwa in Arabian traditional medicine against cardiovascular diseases.

Protective effects of Centella asiatica against isoproterenol-induced myocardial infarction in rats: biochemical, mitochondrial and histological findings

Myocardial infarction (MI) induced by isoproterenol (ISO) is a standardized model to study the beneficial effects of different drugs. The protective effect of Centella asiatica on ISO-induced cardiotoxicity and the antioxidant activity involved in the protection were investigated in rats. Wistar albino rats were used in the present study. Animals were randomly divided into six groups comprising of six animals in each group. MI was induced in rats with ISO (85 mg/kg, sc) twice at an interval of 24 hrs. ISO produced significant alterations in the creatine kinase, biochemical parameters and moderate necrosis in the heart. The effect of Centella asiatica oral treatment for 21 days at two doses (100 mg and 200 mg/kg, body weight) was evaluated against ISO -induced cardiac necrosis. Levels of marker enzymes (LDH and CK) were assessed in serum while antioxidant parameters viz., reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and malondialdehde (MDA) were assayed in heart homogenate. Significant myocardial necrosis, depletion of endogenous antioxidants and increase in serum levels of marker enzymes were observed in ISO-treated animals as compared with the normal control animals. Centella asiatica showed a significant cardioprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation as well as elevated the levels of antioxidant enzymes. The findings of the present study demonstrated that the cardioprotective effects of Centella asiatica on ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation of membrane.

Thymoquinone Protects against Myocardial Ischemic Injury by Mitigating Oxidative Stress and Inflammation.

The present study was aimed at investigating the cardioprotective activity of thymoquinone (TMQ), an active principle of the herb, Nigella sativa, which is used for the management of various diseases. The present study examined the cardioprotective effect of TMQ in isoproterenol- (ISP-) induced myocardial infarction in rats. Myocardial infarction was induced by two subcutaneous injections of ISP (85 mg/kg) at an interval of 24 hr. TMQ (20 mg/kg) was administered orally for 21 days. ISP-treated rats showed depletion of antioxidants and marker enzymes from myocardium along with lipid peroxidation and enhanced levels of proinflammatory cytokines. ISP also induced histopathological alterations in myocardium. Treatment with TMQ prevented the depletion of endogenous antioxidants and myocyte injury marker enzymes and inhibited lipid peroxidation as well as reducing the levels of proinflammatory cytokines. TMQ pretreatment also reduced myonecrosis, edema, and infiltration of inflammatory cells and showed preservation of cardiomyocytes histoarchitecture. The present study results demonstrate that TMQ exerts cardioprotective effect by mitigating oxidative stress, augmenting endogenous antioxidants, and maintaining structural integrity. The results of the present study indicate that TMQ may serve as an excellent agent alone or as adjuvant to prevent the onset and progression of myocardial injury.

Antiapoptotic and antioxidant effects of carvedilol and vitamin E protect against diabetic nephropathy and cardiomyopathy in diabetic Wistar albino rats.

Carvedilol is a novel β-adrenoreceptor blocker, with antioxidant properties inhibiting lipid peroxidation and preventing the depletion of endogenous antioxidants. Moreover, carvedilol was reported to enhance the expression of Bcl-2 gene, which has antioxidant and antiapoptotic effects. There are few researches testing the protective effect of carvedilol on the development of diabetic cardiomyopathy and nephropathy. In this study, we induced diabetes mellitus in male Wistar albino rats. We investigated carvedilol, as well as vitamin E, administrated in healthy and diabetic rats for 6 weeks to compare their effects on biochemical parameters and the expression of Bcl-2 protein in both myocardial and renal tissues by immunohistochemistry. The study showed that the diabetic rats not only had renal dysfunction and more myocardial damage, but also showed lower expression of Bcl-2 protein. Carvedilol and vitamin E treatments were associated with better renal function and less myocardial damage, lower blood glucose, and lipid peroxidation, higher antioxidant capacity, better serum lipids, and higher expression of Bcl-2 protein in diabetic rats. These results indicate that carvedilol and vitamin E treatments partly protect against myocardial and renal damage probably via their antioxidant and antiapoptotic properties in diabetic rats.

Inhibition of UVB-induced skin damage by exopolymers from Aureobasidium pullulans SM-2001 in hairless mice.

Because antioxidants from natural sources may be an effective approach to the treatment and prevention of UV radiation-induced skin damage, the effects of purified exopolymers from Aureobasidium pullulans SM-2001 ('E-AP-SM2001') were evaluated in UVB-induced hairless mice. E-AP-SM2001 consists of 1.7% β-1,3/1,6-glucan, fibrous polysaccharides and other organic materials, such as amino acids, and mono- and di-unsaturated fatty acids (linoleic and linolenic acids) and shows anti-osteoporotic and immunomodulatory effects, through antioxidant and anti-inflammatory mechanisms. Hairless mice were treated topically with vehicle, E-AP-SM2001 stock and two and four times diluted solutions once per day for 15weeks against UVB irradiation (three times per week at 0.18J/cm(2) ). The following parameters were evaluated in skin samples: myeloperoxidase (MPO) activity, cytokine levels [interleukin (IL)-1β and IL-10], endogenous antioxidant content (glutathione, GSH), malondialdehyde (MDA) levels, superoxide anion production; matrix metalloproteases (MMP-1, -9 and -13), GSH reductase and Nox2 (gp91phox) mRNA levels, and immunoreactivity for nitrotyrosine (NT), 4-hydroxynonenal (HNE), caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP). Photoageing was induced by UVB irradiation through ROS-mediated inflammation, which was related to the depletion of endogenous antioxidants, activation of MMPs and keratinocyte apoptosis. Topical treatment with all three doses of E-AP-SM2001 and 5nm myricetin attenuated the UV-induced depletion of GSH, activation of MMPs, production of IL-1β, the decrease in IL-10 and keratinocyte apoptosis. In this study, E-AP-SM2001 showed potent inhibitory effects against UVB-induced skin photoageing. Thus, E-AP-SM2001 may be useful as a functional ingredient in cosmetics, especially as a protective agent against UVB-induced skin photoageing.

Correlation between anthropometric measurement, lipid profile, dietary vitamins, serum antioxidants, lipoprotein (a) and lipid peroxides in known cases of 345 elderly hypertensive South Asian aged 56–64 y–A hospital based study

To address the association of dietary vitamins, anthropometric profile, lipid profile, antioxidant enzymes and lipid peroxidation in hypertensive participant compared with normotensive healthy controls. Dietary intake of vitamins was assessed by 131 food frequency questionnaire items in both hypertensive participants and normotensive age-sex matched healthy controls. The associated changes in serum antioxidants and lipid peroxidation were also assessed along with lipid profile and anthropometric measurements in both groups of subjects under study. Dietary vitamins intake was higher in hypertensive participants excepting for vitamin B2 and ascorbic acid compared to normotensive controls. Anthropometric variables in the hypertensive showed significant differences in weight, body mass index, waist circumference, hip circumference, waist-hip ratio and mid-arm circumference. The total cholesterol, low-density lipoprotein cholesterol, triglyceride were significantly higher (P<0.001) in hypertensive except high-density lipoprotein cholesterol which was significantly higher (P<0.001) in normotensive. The serum endogenous antioxidants and enzyme antioxidants were significantly decreased in hypertensive except serum albumin levels compared to normotensive along with concomitant increase in serum lipoprotein (a) malondialdehyde and conjugated diene levels. Based on the observations, our study concludes that hypertension is caused due to interplay of several confounding factors namely anthropometry, lipid profile, depletion of endogenous antioxidants and rise in oxidative stress.

Skin Photoaging and the Role of Antioxidants in Its Prevention

Photoaging of the skin depends primarily on the degree of ultraviolet radiation (UVR) and on an amount of melanin in the skin (skin phototype). In addition to direct or indirect DNA damage, UVR activates cell surface receptors of keratinocytes and fibroblasts in the skin, which leads to a breakdown of collagen in the extracellular matrix and a shutdown of new collagen synthesis. It is hypothesized that dermal collagen breakdown is followed by imperfect repair that yields a deficit in the structural integrity of the skin, formation of a solar scar, and ultimately clinically visible skin atrophy and wrinkles. Many studies confirmed that acute exposure of human skin to UVR leads to oxidation of cellular biomolecules that could be prevented by prior antioxidant treatment and to depletion of endogenous antioxidants. Skin has a network of all major endogenous enzymatic and nonenzymatic protective antioxidants, but their role in protecting cells against oxidative damage generated by UV radiation has not been elucidated. It seems that skin's antioxidative defence is also influenced by vitamins and nutritive factors and that combination of different antioxidants simultaneously provides synergistic effect.

Licorice treatment prevents oxidative stress, restores cardiac function, and salvages myocardium in rat model of myocardial injury

The present study examined the effects of licorice on antioxidant defense, functional impairment, histopathology, and ultrastructural alterations in isoproterenol (ISP)-induced myocardial injury in rats. Myocardial necrosis was induced by two subcutaneous injection of ISP (85mg/kg) at an interval of 24h. Licorice was administered orally for 30days in the doses of 100, 200, 400, or 800mg/kg. ISP-treated rats showed impaired hemodynamics, left ventricular dysfunction, and caused depletion of antioxidants and marker enzymes along with lipid peroxidation from myocardium. ISP also induced histopathological and ultrastructural alterations in myocardium. Pretreatment with licorice prevented the depletion of endogenous antioxidants and myocyte injury marker enzymes, inhibited lipid peroxidation, and showed recovery of hemodynamic and ventricular functions. Licorice treatment also reduced myonecrosis, edema, and infiltration of inflammatory cells and showed preservation of subcellular and ultrastructural components. Our results demonstrate that licorice exerts cardioprotection by reducing oxidative stress, augmenting endogenous antioxidants, and restoring functional parameters as well as maintaining structural integrity.