Amelioration Of Oxidative Stress Research Articles

Design, synthesis and biological evaluation of triazole-oxadiazole conjugates for the management of cognitive dysfunction

Acetylcholinesterase has been a promising target for the development of putative therapeutics against cognitive decline. The deleterious effect of oxidative stress on the learning and memory paradigms of an individual has also been well documented. In view of this, the present study demonstrates the design, synthesis and pharmacological evaluation of triazole-oxadiazole conjugates. Eighteen novel hybrids (6–23) have been synthesised by employing suitable synthetic procedures and characterized by various spectral and elemental techniques. Further these synthesised compounds were evaluated against behavioural alterations using step down passive avoidance and escape learning protocol at a dose of 0.5 mg/kg with reference to the standard, donepezil. All the synthesised compounds were evaluated for their in vitro acetylcholinesterase (AChE) inhibition at five different concentrations using mice brain homogenate as the source of the enzyme. Biochemical estimation of markers of oxidative stress (lipid peroxidation, superoxide dismutase, glutathione and catalase) has also been carried out to assess the role of synthesised molecules on the oxidative damage induced by scopolamine. The compounds 13, 17 and 23 displayed appreciable activity towards acetylcholinesterase inhibition. These compounds also decreased scopolamine induced oxidative stress, thus serving as promising leads for the amelioration of oxidative stress induced cognitive decline. The molecular docking study performed to predict the binding mode of the compounds also suggested that these compounds bind appreciably to the amino acids present in the active site of the recombinant human acetylcholinesterase (rhAChE). The results indicated that these compounds could be further traversed as inhibitors of AChE and oxidative stress for the treatment of cognitive dysfunction.

Myricetin derivative-rich fraction from Syzygium malaccense prevents high-fat diet-induced obesity, glucose intolerance and oxidative stress in C57BL/6J mice

Aim A high-fat diet (HFD) can lead to obesity and related metabolic disorders. This study evaluated the preventive efficacy of myricetin derivative-rich fraction (MD) from Syzygium malaccense leaf extract against HFD-induced obesity, hyperglycaemia, and oxidative stress in C57BL/6J mice. Methods HFD-fed mice were administered MD (50 mg/kg, 100 mg/kg, and 150 mg/kg) or 2 mg/kg metformin (positive control) orally for 16 weeks. Normal diet and HFD-fed control groups received normal saline. Results MD dose of 50 mg/kg was better than 100 mg/kg and 150 mg/kg in significantly reducing weight-gain, glucose intolerance, insulin resistance, lipid accumulation in liver and kidney, and improving the serum lipid profile. Lowered protein carbonyls and lipid hydroperoxides in urine and tissue homogenates and elevated reduced glutathione, ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant capacity (TEAC) levels in tissue homogenates indicated amelioration of oxidative stress. Conclusion MD has therapeutic value in the prevention and management of obesity, hyperglycaemia, and oxidative stress.

Molecular, Cellular, and Clinical Evidence That Sodium-Glucose Cotransporter 2 Inhibitors Act as Neurohormonal Antagonists When Used for the Treatment of Chronic Heart Failure.

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure. Initially, these drugs were believed to have a profile similar to diuretics or hemodynamically active drugs, but they do not rapidly reduce natriuretic peptides or cardiac filling pressures, and they exert little early benefit on symptoms, exercise tolerance, quality of life, or signs of congestion. Clinically, the profile of SGLT2 inhibitors resembles that of neurohormonal antagonists, whose benefits emerge gradually during sustained therapy. In experimental models, SGLT2 inhibitors produce a characteristic pattern of cellular effects, which includes amelioration of oxidative stress, mitigation of mitochondrial dysfunction, attenuation of proinflammatory pathways, and a reduction in myocardial fibrosis. These cellular effects are similar to those produced by angiotensin converting enzyme inhibitors, β‐blockers, mineralocorticoid receptor antagonists, and neprilysin inhibitors. At a molecular level, SGLT2 inhibitors induce transcriptional reprogramming of cardiomyocytes that closely mimics that seen during nutrient deprivation. This shift in signaling activates the housekeeping pathway of autophagy, which clears the cytosol of dangerous cytosolic constituents that are responsible for cellular stress, thereby ameliorating the development of cardiomyopathy. Interestingly, similar changes in cellular signaling and autophagic flux have been seen with inhibitors of the renin‐angiotensin system, β‐blockers, mineralocorticoid receptor antagonists, and neprilysin inhibitors. The striking parallelism of these molecular, cellular, and clinical profiles supports the premise that SGLT2 inhibitors should be regarded as neurohormonal antagonists when prescribed for the treatment of heart failure with a reduced ejection fraction.

Effect of fish oil and telmisartan on dehydroepiandrosterone-induced polycystic ovarian syndrome in rats: The role of oxidative stress, transforming growth factor beta-1, and nuclear factor kappa B.

Our aim was to explore the effect of telmisartan and/or fish oil on dehydroepiandrosterone (DHEA)‐induced PCOS in rats. Sixty female rats were divided into six equal groups as follows: Control; DHEA‐induced PCOS; DHEA + Telmisartan; DHEA + Fish oil; DHEA + Carboxymethyl cellulose; and DHEA + Telmisartan +Fish oil group. Plasma sex hormones, anthropometric measurements, and the glycemic indices were measured. Tissue oxidative stress parameters and the proinflammatory cytokines were assessed. The ovaries were subjected to histopathological and electron microscopic examination. Telmisartan and/or fish oil induced significant improvement of insulin resistance with amelioration of oxidative stress and inflammation compared to PCOS group. Also, telmisartan and/or fish oil restored the hormonal levels and the anthropometric measurements to the normal values. This was significant with telmisartan/fish oil combination compared to the use of each of these agents alone. In conclusion, this combination may represent a promising hope for amelioration of PCOS.

SIRT1-mediated amelioration of oxidative stress in kidney of alcohol-aflatoxin-B1-induced hepatocellular carcinoma by resveratrol is catalase dependent and GPx independent.

Hepatocellular carcinoma (HCC) is a type of primary liver cancer and dietary exposure to aflatoxins is a major risk factor of HCC. The current study aimed to assess the role of resveratrol and nicotinamide in renal toxicity during alcohol-aflatoxin-B1-induced HCC. The results revealed that resveratrol treatment normalized the level of urea, lipid peroxidation, lactate and lactate dehydrogenase, which were increased in HCC. It also downregulated the increased expression of sirtuin 1 in HCC kidney. Furthermore, amelioration of oxidative stress in kidney of HCC rats by resveratrol was observed to be catalase dependent and glutathione peroxidase independent.

Effects of dietary quercetin on the antioxidative status and cecal microbiota in broiler chickens fed with oxidized oil

This study was conducted to evaluate the effects of quercetin on the antioxidant ability, intestinal barrier functions, and cecal microbiota in broiler chickens fed with oxidized soya oil. Four hundred eighty male Arbor Acres broilers were randomly assigned to 5 treatments, each involving 8 cages (12 birds per cage). The treatment groups were as follows: the control group, birds fed with basal diets containing oxidized oil, and birds fed with basal diets containing oxidized oil and supplemented with 200 ppm of quercetin, 400 ppm of quercetin, and 800 ppm of quercetin. The results showed that dietary supplementation with quercetin at a dose of 400 ppm or 800 ppm alleviated the increased serum malondialdehyde (MDA) level induced by oxidized oil on day 11 (P = 0.005) and reversed the increased MDA level in the mucosa on day 11 (P = 0.021). Quercetin significantly upregulated the transcription of nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream genes such as catalase (P < 0.001), superoxide dismutase 1 (P < 0.001), glutathione peroxidase 2 (P = 0.018), heme oxygenase-1 (HO-1) (P = 0.0), and thioredoxin (P = 0.002) and reversed the mRNA expression of HO-1 (P = 0.007) in the ileal mucosa. Tight junction protein 1 was only downregulated by oxidized oil (P = 0.013). In addition, quercetin (800 ppm) alleviated the decreased mRNA expression of mucin 2 (MUC2), which contributed to the intestinal chemical barrier (P = 0.039). The supplemental dose of 400 ppm of quercetin was able to promote Lactobacillus in the cecum, which enhanced the gastrointestinal tract health. In summary, these results indicated that quercetin ameliorated the oxidized oil–induced oxidative stress by upregulating the transcription of Nrf2 and its downstream genes to restore redox balance and reinforced the intestinal barrier via higher expression and secretion of MUC2 and facilitating the growth of Lactobacillus in the cecum. Therefore, quercetin could be a potential feed additive that can be applied in poultry production for amelioration of oxidative stress caused by oxidized oil and preventing the potential invasion of exogenous pathogens.

Targeting oxidative stress, transforming growth factor beta-1, and the mammalian target of rapamycin by valproic acid to ameliorate bleomycin-induced scleroderma

Objective: To explore the possible ameliorative effect of valproic acid on the experimental model of skin fibrosis induced by bleomycin. Materials and Methods: Forty male BALB/c mice were divided into four equal groups as follows: control group, bleomycin group, bleomycin + Valproic acid group, and Valproic acid group. Mice were assessed for their body weight every 3 days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha, interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Furthermore, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Results: Administration of Valproic acid to bleomycin-treated mice resulted in the restoration of the body weight with significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. Conclusion: Valproic acid has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.

Prunus amygdalus extract exert antidiabetic effect via inhibition of DPP-IV: in-silico and in-vivo approaches

Prunus amygdalus (PA) is a popular invasive seed utilized in the management of diabetes in Jammu and Kashmir, India. The objective of the current study was to scrutinize the antidiabetic effect of Prunus amygdalus (PA) against Streptozotocin (STZ) induced diabetic rats and explore the possible mechanism of action at cellular and sub-cellular levels. Box Benkan Design (BBD) was performed to determine the effect of PA powder to methanol, extraction time and extraction temperature on DPPH and ABTS free radical scavenging activity of decoction. In-silico study was performed on GLUT1 (5EQG) and dipeptidyl peptidase IV (DPPIV) (2G63) protein. Type II diabetes mellitus was initiated by single intra-peritoneal injection of STZ. The Blood Glucose Level (BGL) and body weight were estimated at regular interval of time. The different biochemical parameters such as hepatic, antioxidant, and lipid parameters were estimated. At end of the study, pancreas was used for histopathological observation. The variation in DPPH antiradical scavenging activity 40.0–90.0% and ABTS antiradical scavenging activity 34–82%, were estimated respectively. STZ induced DM rats showed increased BGL at end of the experimental study. PA treatment significantly (p < 0.001) down-regulated the BGL level. PA significantly (p < 0.001) altered the biochemical, hepatic and antioxidant parameters in a dose-dependent manner. Histopathological examination demonstrated the constructive mass of β-cells in pancreas. Overall, the current study indicates that the PA treatment down-regulated the hyperglycemic, oxidative stress and hyperlipidaemia in diabetic rats, due to inhibition of enzymes or amelioration of oxidative stress. Communicated by Ramaswamy H. Sarma

Zinc exerts its renal protection effect on arsenic-exposed common carp: A signaling network comprising Nrf2, NF-κB and MAPK pathways

Epidemiological and laboratory investigations have extensively indicated that arsenic exposure accounts for several kidney diseases. Zinc has been suggested as a possible natural preventive and therapeutic agent. This study is designed to explore the beneficial effect of zinc supplementation against arsenic-induced renal toxicity in common carp, and the results point to signaling pathway possibly compromised. In the present study, renal injury was induced in common carp by waterborne exposure to arsenic (2.83 mg/L) for 30 days, and zinc (1 mg/L) was simultaneously supplemented. First, the arsenic-exposed fish showed histological and functional renal alterations (indicated by hematoxylin-eosin staining, biochemical indexes and a TUNEL assay). Moreover, as a reactive oxygen species (ROS) stimulant, arsenic was found to induce oxidative toxicity as determined by increased renal ROS, malondialdehyde, protein carbonyl and 8-hydroxydeoxyguanosine levels. When antioxidant-mediation attempts (through superoxide dismutase and glutathione)-mediated to restore homeostasis failed and ROS increased to extreme levels, inflammation (indicated by elevated inducible nitric oxide synthetase, tumor necrosis factor-alpha and interleukins levels) and apoptosis (through both mitochondrial- and death receptor-dependent pathways) were triggered. However, abnormalities in the upstream mediators Nrf2, NF-κB and MAPK were significantly ameliorated and blocked by treatment with zinc. In conclusion, zinc exerts a substantial protective effect against arsenic-triggered subchronic renal injury in common carp via the amelioration of oxidative stress, suppression of apoptosis and reduced inflammation through Nrf2, NF-κB and MAPK signaling.

Diosgenin Attenuates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats: Underlying Mechanisms

Objective: Prolonged diabetes mellitus causes impairments of cognition and attentional dysfunctions. Diosgenin belongs to a group of steroidal saponins with reported anti-diabetic and numerous protective properties. This research aimed to assess the effect of diosgenin on beneficially ameliorating learning and memory decline in a rat model of type 1 diabetes caused by streptozotocin (STZ) and to explore its modes of action including involvement in oxidative stress and inflammation.Methods:Rats were assigned to one of four experimental groups, comprising control, control under treatment with diosgenin, diabetic, and diabetic under treatment with diosgenin. Diosgenin was given daily p.o. (40 mg/kg) for 5 weeks. Results: The administration of diosgenin to the diabetic group reduced the deficits of functional performance in behavioral tests, consisting of Y-maze, passive avoidance, radial arm maze, and novel object discrimination tasks (recognitive). Furthermore, diosgenin treatment attenuated hippocampal acetylcholinesterase activity and malon­dialdehyde, along with improvement of antioxidants such as superoxide dismutase and glutathione. Meanwhile, the hippocampal levels of inflammatory indicators, namely interleukin 6, nuclear factor-κB, toll-like receptor 4, tumor necrosis factor α, and astrocyte-specific biomarker glial fibrillary acidic protein, were lower and, on the other hand, tissue levels of nuclear factor (erythroid-derived 2)-related factor 2 were elevated upon diosgenin administration. Besides, the mushroom-like spines of the pyramidal neurons of the hippocampal CA1 area decreased in the diabetic group, and this was alleviated following diosgenin medication. Conclusions: Taken together, diosgenin is capable of ameliorating cognitive deficits in STZ-diabetic animals, partly due to its amelioration of oxidative stress, inflammation, astrogliosis, and possibly improvement of cholinergic function in addition to its neuroprotective potential.

Nitrogen Deprivation-Induced Production of Volatile Organic Compounds in the Arachidonic-Acid-Accumulating Microalga Lobosphaera incisa Underpins Their Role as ROS Scavengers and Chemical Messengers

The green microalga Lobosphaera incisa accumulates long-chain polyunsaturated arachidonic acid sequestered in triacylglycerols under nitrogen (N)-starvation conditions. Many of L. incisa’s physiological and metabolic responses to N-starvation have been previously investigated. However, the temporal dynamics of the volatile organic compounds (VOCs) under different N availability and their role in L. incisa stress responses have yet to be elucidated. Here, we investigated the VOC profiles of L. incisa to reveal their emission patterns, and proposed their physiological roles under N-starvation. Using gas chromatography-mass spectrometry, 42 and 19 VOCs were identified in the algal biomass (AVOCs) and in the medium (MVOCs), respectively, belonging to alkanes, alkenes, benzenoids, esters, fatty alcohols, fatty aldehydes, fatty acids (FAs), FA esters, ketones, and terpenoids; most of these are the oxidative products of FAs or photosynthetic pigment degradation. The discriminant AVOCs and MVOCs produced under N-starvation were identified by principal component analyses and hierarchical clustering. A significant treatment- and time-dependent increase in volatile FAs and their oxidative products was observed in the algal biomass and medium under N-starvation as compared to N-replete controls, following a similar pattern as reactive oxygen species (ROS) production. This suggests that VOCs may be involved in ROS scavenging. Despite the increase in total VOCs, terpenoids and alkenes decreased significantly with N-starvation duration, along with chloroplast degradation. Transcriptomic data supported the VOC patterns and revealed the upregulation of genes involved in fatty aldehyde, fatty alcohol, and ketone synthesis, including lipoxygenase, thioesterase, and fatty acyl CoA reductase, along with a decrease in the expression of genes putatively implicated in alkene biosynthesis. Several VOCs were identified as potential biotechnological targets, and their putative biosynthetic pathways were proposed, which could be genetically manipulated to enhance the yields of high value products. We conclude that VOCs may play an important role in stress metabolism, ROS scavenging, and the amelioration of oxidative stress under N-starvation. Also, VOCs released in the medium may communicate the signal to neighboring cells, thus priming them to adjust their metabolic activities to adapt to N-starvation conditions, indicating that the function of VOCs as chemical signaling messengers is conserved from microalgae to higher plants.

MOF-encapsulated nanozyme enhanced siRNA combo: Control neural stem cell differentiation and ameliorate cognitive impairments in Alzheimer's disease model

Neural stem cells (NSC) transplantation is garnering considerable attention in the treatment of neurodegenerative diseases that are associated with cognitive decline. Current methods are mainly based on neuron-directional differentiation and NSC niche components majorization to promote neurogenesis. Unfortunately, the pathologically high level of oxidative stress will damage the neurons derived from NSC during therapy, compromising the neurogenesis effect. Herein, a facile and effective strategy has been presented for modulation of neuron-directional differentiation and amelioration of oxidative stress by integrating antioxidative nanozymes (ceria) into metal-organic frameworks (MOF) for synergistically enhancing neurogenesis. Specially, small interfering RNA (siSOX9) and retinoic acid (RA) are loaded in the MOF. The H2O2-responsive MOF would release cargos in the lesion area to promote neuron-directional differentiation. Moreover, the integrated ceria can perform robust SOD and CAT mimetic activities, which are capable of eliminating ROS and circumventing its oxidative damage to newborn neurons, leading to the longer survival rate and more enhanced outgrowth of the newborn neurons. With the gratifying drug delivery efficiency of MOF and excellent antioxidative capacity of nanozymes, the rational-designed nanoparticles can considerably promote neurogenesis and improve the cognitive function of aged 3 × Tg-AD (triple transgenic AD mouse model) mice. Our work provides a new way to promote nerve regeneration with the help of nanozymes.

Improvement of NRF2 gene expression and antioxidant status in patients with type 2 diabetes mellitus after supplementation with omega-3 polyunsaturated fatty acids: A double-blind randomised placebo-controlled clinical trial

BackgroundNrf2 is a transcription factor that induces the expression of several proteins with antioxidant properties such as sestrin2 (Sesn2) and is therefore considered as the major regulator of anti-oxidative defence system. ObjectivesThe aim of this research was to study the effect of supplementation with n-3 PUFAs on the antioxidant status and the gene expression of Nrf2 and Sestrin2 (Sesn2) in patients with type 2 diabetes mellitus (T2DM). ParticipantsSixty patients with T2DM were enrolled in a placebo-controlled, double-blind, randomised clinical trial. Intervention and designThe participants were randomly allocated to two intervention groups receiving either n-3 PUFAs (2,700 mg/day) (n = 30) or placebo soft gels containing 900 mg of edible paraffin (n = 30). The main outcome measures were the expression of Sesn2 and Nrf2 genes which were assessed in peripheral blood mononuclear cells (PBMCs) after RNA extraction and cDNA synthesis by real-time PCR. Total antioxidant status in plasma samples was also measured based on the ferric reducing ability of plasma. ResultsNRF2 gene expression was significantly increased in n-3 PUFA-supplemented subjects, compared with the placebo group. Plasma total antioxidant status was also significantly augmented in n-3 PUFA-supplemented subjects. SESN2 gene expression was not significantly affected by n-3 PUFA supplementation although a slight up-regulation was observed. ConclusionSupplementation with n-3 PUFAs enhanced NRF2 gene expression and improved overall antioxidant capacity and thus might be considered beneficial in the amelioration of oxidative stress and prevention of T2DM complications.Trial registration: IRCT20150926024198N4.

Allium cepa fraction attenuates STZ-induced dementia via cholinesterase inhibition and amelioration of oxidative stress in mice.

Background An earlier study demonstrated significant antioxidant and anticholinesterase activities of hydromethanol extract (HME) of Allium cepa. The aim of the study was to investigate the component responsible for these activities followed by an in vivo study. Methods In vitro antioxidant and anticholinesterase activities of standardized ethylacetate fraction (EAF) of HME were assessed. Bioactivity-guided fractionation showed that, as compared with its subfractions, EAF had most significant activity in 2,2-diphenyl-1-picrylhydrazyl and Ellman assays. Thus, EAF was further examined using a streptozotocin (STZ)-induced model of Alzheimer's disease in mice. STZ was injected intracerebroventricularly on days 1 and 3 (3 mg/kg) in mice. EAF was thereafter administered (42, 84, and 168 mg/kg b.w./day p.o.) from days 9 to 22. The Morris water maze test was used to evaluate learning and memory in mice. Acetylcholinesterase (AChE) activity and oxidative stress markers were assessed in the brain homogenates of mice. Additionally, histopathological studies were performed to observe effects in the brain at the cellular level. EAF was standardized based on quercetin and quercetin 4'-O-glucoside content using a validated thin layer chromatography densitometric method. Results STZ produced significant (p < 0.05) memory impairment along with oxidative stress and a cholinergic deficit in mice. EAF treatment ameliorated STZ-induced behavioral deficits and biochemical alterations in mice in a significant and dose-dependent manner. Conclusions Our results show that EAF is efficacious in improving memory and learning via AChE inhibition and antioxidant activity in the mice brain. Thus, AC could be explored further to find out a lead candidate for Alzheimer's disease.

The role of garlic oil in the amelioration of oxidative stress and tissue damage in rohu Labeo rohita treated with silver nanoparticles

Aquatic contamination with silver nanoparticles (Ag-NPs) can cause toxicity in target organisms that are directly exposed to them. Oxidative stress and tissue alterations are potential endpoints of Ag-NPs toxicity. We determined whether garlic oil can ameliorate the effects of toxicity induced by amine-coated and spherical Ag-NPs in 100 ± 5 g freshwater rohu Labeo rohita. The stock fish were placed in tanks with continuous water supply. There were three treatments and a control group, each with three replicates comprising five fish each. The treatments were: garlic only, Ag-NPs only, and garlic plus Ag-NPs. The Ag-NPs (30 mg/L) was supplied in water, whereas garlic oil (50 µl/kg) was given to the fish through a prepared feed. The treatment duration was 28 days. In the control and garlic oil treatment there were no observed alterations in fish. The Ag-NP treatment initiated inflammation and necrosis in hepatic parenchyma, which resulted in venous congestion. Garlic oil treatment reduced vascular congestion in hepatic tissues. Ag-NPs also induced cellular vacuolization and the build-up of a yellow pigment. Inflammatory gill filament cartilage and lamellae were observed, as were swelling and collapse of lamellae, accumulation of macrophages, and necrosis and fusion of secondary lamellae in gill sections of Ag-NP-treated fish. Garlic oil ameliorated these changes, although some alterations like fused secondary lamellae, separation between the epithelium and lamellae, and accumulation of macrophages were still recorded in gill sections of garlic-treated fish. Garlic oil increased the activity of antioxidants (superoxide dismutase, catalase, glutathione S-transferase and glutathione) and caused a reduction in lipid peroxidation and/or MDA content. Furthermore, garlic oil treatment also improved measured hematologic parameters. This study confirms the role of garlic as a natural antioxidant for the amelioration of oxidative stress and histological and hemotologic changes in fish exposed to Ag-NPs.

Renoprotective Effects of Gallic Acid Against Gentamicin Nephrotoxicity Through Amelioration of Oxidative Stress in Rats

Gallic acid (GA), as a strong antioxidant, was selected in this study to investigate its possible nephroprotective effects against gentamicin (GM)-induced nephrotoxicity. Twenty-four rats were separated into three groups (n=8): group 1 (control group) received saline (0.5 mL/day), group 2 (GM group) received GM (100 mg/kg/day), and group 3 (treated group) received GM (100 mg/kg/day) and GA (100mg/kg/day). All treatments were performed intraperitoneally for 12 days. After 12 days, the rats were euthanized, and kidneys were removed immediately. For serum preparation, blood samples were collected before killing. Kidney paraffin sections were prepared from one of the kidneys and stained by the periodic acid-Schiff process. GA significantly decreased GM-induced renal histopathological injuries, including tubular necrosis, tubular cast, and leucocyte infiltration compared with the GM group. Additionally, GA significantly improved proteinuria, serum levels of urea and creatinine, and serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with nephrotoxic animals. Furthermore, GA caused a significant improvement in the levels of cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and cardiac risk ratios 1 and 2 in comparison with nephrotoxic animals. GA administration was observed to significantly improve the levels of lipid peroxidation, nitric oxide (NO), and glutathione (GSH) compared with the GM group. Finally, the activities and gene expression levels of catalase (CAT) and glutathione peroxidase (GPX) significantly increased following GA administration compared with the GM group. Our results indicated that GA has potential protective effects against GM nephrotoxicity by reducing oxidative stress in rats.

Protective mechanisms of piperine against renal ischemia–reperfusion injury in rats

Background: Renal ischemia–reperfusion injury (IRI) is a major clinical problem associated with kidney transplantation, leading to high mortality and morbidity. IRI involves activation of oxidative stress and inflammatory pathways, eventually leading to cell death and organ failure. Piperine is a phenolic active ingredient of black pepper, which showed promising antioxidant and anti-inflammatory potential. Objectives: We hypothesized that piperine would protect against renal IRI in rats via inhibition of oxidative stress and inflammation. Materials and Methods: Male Sprague Dawley rats were subdivided into four groups; sham, IR, IR + piperine, and sham + piperine. All animals have been treated for 4 days with either vehicle or piperine (100 mg/kg/day). One hour after the last piperine or vehicle administration, animals were subjected to bilateral renal ischemia for 45 min by clamping both renal pedicles, followed by reperfusion for 24 h. At the end of the experiments, kidneys were harvested for the determination of lipid peroxidation (malondialdehyde [MDA]), reduced glutathione (GSH), inflammatory and apoptotic markers, and histopathology. Serum levels of creatinine and urea have been determined. Results: Induction of renal IR increased renal oxidative stress (increased MDA and decreased GSH) and the expression levels of inflammatory and proapoptotic genes (nuclear factor-kappa B, inducible nitric oxide synthase, cyclooxygenase-2, and caspase-3). Moreover, serum levels of creatinine and urea were significantly elevated. Alternatively, pretreatment of the animals with piperine resulted in normalization of these parameters. Conclusion: The results showed that piperine pretreatment protects against IRI in rat kidneys via mechanisms involving amelioration of oxidative stress along with inflammatory and apoptotic pathways.

Diosmin Regulates Oxidative Stress and Inflammatory Marker Levels in N-Methyl-N-Nitrosourea-Induced Gastric Carcinogenesis in Rats.

Gastric cancer is the most typical oncological illness globally. Though the incidence of gastric cancer has dropped dramatically over the last few years, the survival rate is yet concerning due to poor diagnostic strategy. The etiology of gastric cancer is majorly associated with dietary factors. For this reason, application of nontoxic natural agents with anticancer effects for patients is needed. Diosmin has been commonly utilized to treat various diseases both traditionally and now clinically. However, its effect on gastric carcinogenesis remains unclear. The effects of diosmin were used to evaluate how N-methyl-N-nitrosourea (MNU) induces gastric carcinogenesis in rats. The general and gross assessment of MNU in experimental animals was tabulated. Biological tumor markers (gastrin, ALP, LDH, and γ-GT) were examined. Oxidative markers (LPO) and antioxidative markers (GSH, vitamin E, and vitamin C) were determined. In addition, inflammatory cytokines (thioredoxin, glutaredoxin, NF-κB, TNF-α, IL-6, PGE2) were explored and justified with histopathological studies. Overall, the results showed positive anticancer activity demonstrated by improved body weight, reduced tumor rate, decreased oxidative marker value by increased antioxidative rate, and suppressed tumor biomarkers and inflammatory cytokines. The histopathological analysis was congruent with the data observed. Our conclusion that diosmin exerts its anticancer activity by up-regulation of antioxidants which might be responsible for amelioration of oxidative stress and inflammatory cytokines in carcinogenesis to prevent gastric cancer.

Citicoline Improves Human Vigilance and Visual Working Memory: The Role of Neuronal Activation and Oxidative Stress.

Introduction:Psychomotor performance task is used to assess the arousal and cognitive functions of the central nervous system. Alternatively, human visual working memory reflects the capability of the individual’s short-term memory. Psycho-mental stimuli are linked to the stimulation of Malondialdehyde (MDA) formations. Citicoline is a nootropic nucleotide agent with a favorable effect on the augmentation of human memory and cognitive function. Thus, the purpose of this study was to determine the effect of citicoline on human vigilance, visual working memory, and oxidative stress using healthy volunteers.Methods:40 healthy volunteers were enrolled and divided into two groups: group A: 20 volunteers received 500mg/day starch capsule for two weeks and group B: 20 volunteers received 500mg/day citicoline capsule for two weeks. Human vigilance, visual working memory, and oxidative stress markers of each volunteer were assessed before and after citicoline and placebo intake. The obtained data were analyzed by SPSS regarding P<0.05 as statistically significant.Results:Placebo had no significant effect on human vigilance and visual working memory after two weeks of therapy (P>0.05), whereas citicoline improved most variables of psychomotor performances and working memory (P<0.01). Placebo significantly increased serum MDA levels from 19.44±2.11 to 29.66±3.28 nmol/mL (P=0.0001), while citicoline significantly decreased MDA serum levels from 19.11±2.66 to 15.63±1.33 nmol/mL (P=0.0001).Conclusion:Citicoline improves human psychomotor vigilance, arousal, and visual working memory with significant amelioration of oxidative stress compared with placebo.

The Effect of Cupressus Sempervirens on Ulcerative Colitis: Do Pathological Changes Improve by Oxidative Stress Amelioration?

 &#x0D; Â