Advanced Oxidation Protein Products Research Articles

Differential Responses of Young and Old Erythrocytes Stored with Vitamin C and Vitamin E in Additive Solution-7.

Oxidative stress (OS) causes biochemical and morphological alterations in erythrocytes. The primary factors contributing to OS are aging and storage. Antioxidants significantly alleviate OS. Therefore, this study aimed to investigate the response of young and old erythrocytes to vitamin C and vitamin E during storage. Erythrocytes were separated into young and old by the Percoll method. Each erythrocyte subpopulation was categorized into the i) Control (additive solution-7 [AS-7]) and ii) vitamin C and vitamin E in AS-7 (VC+VE) groups and stored for 21 days at 4°C. OS, antioxidant, and aging markers were analyzed on days 1, 14, and 21. The activity of antioxidant enzymes was similar throughout storage in young cells. However, superoxide dismutase activity elevated in old cells (Control and VC+VE) on days 1 and 21. Catalase (CAT) activity increased on days 14 and 21, whereas glutathione peroxidase (GPX) increased on days 1 and 14 in old Controls. However, in old VC+VE, CAT increased on day 21 and GPX increased on day 1. Advanced oxidation protein products, superoxides, glutathione, and uric acid increased in old cells throughout storage. Malondialdehyde decreased in old VC+VE compared with old Control on days 14 and 21. Sialic acids and glutamate oxaloacetate transaminase activity were higher in young cells compared to old cells. Young cells exhibited lower oxidative changes throughout storage. Vitamin C and vitamin E were effective in maintaining the redox balance in old cells. These findings emphasize the need for specific approaches for different subpopulations during erythrocyte banking.

Novel Properties of Old Propranolol-Assessment of Antiglycation Activity through In Vitro and In Silico Approaches.

Hypertension has earned the "silent killer" nickname since it may lead to a number of comorbidities, including diabetes and cardiovascular diseases. Oxidative stress and protein glycation play vital roles in the pathogenesis of hypertension. Several studies have shown that they profoundly account for vascular dysfunction, endothelial damage, and disruption of blood pressure regulatory mechanisms. Of particular note are advanced glycation end products (AGEs). AGEs alter vascular tissues' functional and mechanical properties by binding to receptors for advanced glycation end products (RAGE), stimulating inflammation and free radical-mediated pathways. Propranolol, a nonselective beta-adrenergic receptor antagonist, is one of the most commonly used drugs to treat hypertension and cardiovascular diseases. Our study is the first to analyze propranolol's effects on protein glycoxidation through in vitro and in silico approaches. Bovine serum albumin (BSA) was utilized to evaluate glycoxidation inhibition by propranolol. Propranolol (1 mM) and BSA (0.09 mM) were incubated with different glycating (0.5 M glucose, fructose, and galactose for 6 days and 2.5 mM glyoxal and methylglyoxal for 12 h) or oxidizing agents (chloramine T for 1 h). Biomarkers of protein glycation (Amadori products (APs), β-amyloid (βA), and advanced glycation end products (AGEs)), protein glycoxidation (dityrosine (DT), kynurenine (KYN), and N-formylkynurenine (NFK)), protein oxidation (protein carbonyls (PCs), and advanced oxidation protein products (AOPPs)) were measured by means of colorimetric and fluorimetric methods. The scavenging of reactive oxygen species (hydrogen peroxide, hydroxyl radical, and nitric oxide) and the antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion chelating (FIC) assays)) of propranolol were also evaluated. Additionally, in silico docking was performed to showcase propranolol's interaction with BSA, glycosides, and AGE/RAGE pathway proteins. The products of protein glycation (↓APs, ↓βA, ↓AGEs), glycoxidation (↓DT, ↓KYN, ↓NFK), and oxidation (↓PCs, ↓AOPPs) prominently decreased in the BSA samples with both glycating/oxidizing factors and propranolol. The antiglycoxidant properties of propranolol were similar to those of aminoguanidine, a known protein oxidation inhibitor, and captopril, which is an established antioxidant. Propranolol showed a potent antioxidant activity in the FIC and H2O2 scavenging assays, comparable to aminoguanidine and captopril. In silico analysis indicated propranolol's antiglycative properties during its interaction with BSA, glycosidases, and AGE/RAGE pathway proteins. Our results confirm that propranolol may decrease protein oxidation and glycoxidation in vitro. Additional studies on human and animal models are vital for in vivo verification of propranolol's antiglycation activity, as this discovery might hold the key to the prevention of diabetic complications among cardiology-burdened patients.

CYP2E1 mediated advanced oxidation protein products exacerbate acetaminophen induced drug-derived liver injury in vitro and in vivo

Drug-induced liver injury (DILI) is prevalent in the treatment of chronic kidney disease (CKD). Advanced oxidation protein products (AOPPs) are markers of CKD progression and participate in the occurrence and development of liver diseases. However, the mechanisms underlying the regulation of DILI in CKD have not been established. Herein, we demonstrate the involvement of Cytochrome p450 2E1 (CYP2E1) in DILI induced by AOPPs is exacerbated by exposure to acetaminophen (APAP). We used a adenine-induced CKD model, a model of DILI induced by APAP, and the AOPPs model was generated by intraperitoneal injection. The decline in renal function was associated with a significantly increased concentration of Scr, BUN and AOPPs, and renal tissue fibrosis. The ALT, AST, and AOPPs levels and liver tissue necrosis increased significantly in CKD model group compared with the sodium carboxymethyl cellulose (CMCNa) group. In the AOPPs model, compared to the PBS controls, ALT, AST, and AOPP levels, and liver tissue necrosis increased significantly. In HepG2 or L0–2 cell lines, cell survival was significantly reduced in the AOPP + APAP treatment and CYP2E1 protein expression was increased. FPS-ZM1 or NAC attenuated the hepatocyte toxicity induced by AOPP + APAP and suppression of CYP2E1 expression. AOPPs exacerbated APAP-induced DILI through CYP2E1 signaling pathways. Protein uremic toxins, such as AOPPs, can modify drug toxicity in patients with CKD. This study provides new a rationale to reduce the generation of DILIs in clinical treatment in patients with CKD. AOPPs targeting may present a novel approach to reduce the occurrence of DILI.

Investigating the Anti-inflammatory Effect of Quinoline Derivative: N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine Hydrochloride Loaded Soluble Starch Nanoparticles Against Methotrexate-induced Inflammation in Experimental Model

BackgroundIt is necessary to develop advanced therapies utilizing natural ingredients with anti-inflammatory qualities in order to lessen the negative effects of chemotherapeutics.ResultsThe bioactive N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine hydrochloride (NIQBD) was synthesized. After that, soluble starch nanoparticles (StNPs) was used as a carrier for the synthesized NIQBD with different concentrations (50 mg, 100 mg, and 200 mg). The obtained StNPs loaded with different concentrations of NIQBD were coded as StNPs-1, StNPs-2, and StNPs-3. It was observed that, StNPs-1, StNPs-2, and StNPs-3 exhibited an average size of 246, 300, and 328 nm, respectively. Additionally, they also formed with homogeneity particles as depicted from polydispersity index values (PDI). The PDI values of StNPs-1, StNPs-2, and StNPs-3 are 0.298, 0.177, and 0.262, respectively.In vivo investigation of the potential properties of the different concentrations of StNPs loaded with NIQBD against MTX-induced inflammation in the lung and liver showed a statistically substantial increase in levels of reduced glutathione (GSH) accompanied by a significant decrease in levels of oxidants such as malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), matrix metalloproteinase 9/Gelatinase B (MMP-9), and levels of inflammatory mediators including interleukin 1-beta (IL-1β), nuclear factor kappa-B (NF-κB) in both lung and liver tissues, and a significant decrease in levels of plasma homocysteine (Hcy) compared to the MTX-induced inflammation group. The highly significant results were obtained by treatment with a concentration of 200 mg/mL.Histopathological examination supported these results, where treatment showed minimal inflammatory infiltration and congestion in lung tissue, a mildly congested central vein, and mild activation of Kupffer cells in liver tissues.ConclusionCombining the treatment of MTX with natural antioxidant supplements may help reducing the associated oxidation and inflammation.

DIET-INDUCED CHANGES IN SOME PARAMETERS OF OXIDATIVE SATUS IN WISTAR RATS – COMPARISON BETWEEN THREE DIFFERENT DIETS AND EFFECTS OF REPLACING DIETARY SUCROSE WITH STEVIOL GLYCOSIDES

PURPOSE: The aim of the study was to evaluate the effects of a high-fat diet, high-carbohydrate diet and a combined high-fat high-carbohydrate diet on some parameters of oxidative status in a rat experimental model, and to test the potential positive effects of replacing sucrose with stevia extract in some of the diets. METHODS: The following parameters of oxidative status were measured: advanced oxidation protein products (AOPP), catalase, glutathione and ferric reducing ability of plasma (FRAP). Fifty-six male Wistar rats were used in the study. Rats were divided into seven groups: 1) group BD (before diet), in which parameters were measured before beginning of the diet; and six more groups in which parameters were measured after 5 weeks on the respective dietary regimen, as follows: 2) group SD (standard diet); 3) group HFD (high-fat diet); 4) group HCHD (high-carbohydrate diet); 5) group HFHCHD (high-fat high-carbohydrate diet); 6) group SD-S (standard diet with added stevia extract); 7) group HFD-S (high-fat diet with added stevia extract). RESULTS: Diets enriched with fats and carbohydrates induce significant changes in some of the oxidative status parameters. CONCLUSIONS: A five-week experimental diet enriched with fats and carbohydrates has the potential to disrupt pro-oxidant / antioxidant balance in rats.

Anaerobic glycolysis and oxidative stress interrelation in erythrocytes under administration of Cornus mas L. fruit extracts to rats with streptozotocin-induced diabetes mellitus

Background. In diabetes mellitus (DM), analysis of changes in the biochemical profile of erythrocytes is the important stage of complex scientific research to clarify the mechanism of action of medicinal products based on plant raw materials. The fruits of Cornus mas L. are widely known. The biologically active compounds of these fruits show multiple biological effects. However, the effect of the fruit extracts of cornelian cherry on the functional state of erythrocytes in diabetes has not been sufficiently studied. The high glucose concentration in erythrocytes induces various structural and functional changes, which lead to numerous disturbances in their metabolism. Glucose transported into erythrocytes by facilitated diffusion via GLUT2 undergoes catabolic breakdown in anaerobic glycolysis (90 % of all glucose) and pentose phosphate pathway (the rest 10 %). ATP and reduced coenzymes of NADH + H+ and NADPH + H+ formed due to metabolism participate in maintaining the structure of hemoglobin. Enzymes of the antioxidant defense system, which prevent hemoglobin oxidation into methemoglobin, are especially important. Hyperglycemia and the development of oxidative stress in diabetes are the cause of a decrease in the activity of antioxidant enzymes and the accumulation of ligand forms of hemoglobin (HbCO2, MetHb, HbA1c). Therefore, the work aimed to investigate the effect of extracts of red and yellow fruits of Cornus mas L. on the content of end products of the glycolytic breakdown of glucose in erythrocytes and biochemical markers of the antioxidant status of these blood cells in rats with streptozotocin-induced diabetes. Materials and Methods. DM 1 type in animals was induced by intraperitoneal injection of streptozotocin. Experiments were performed on male Wistar rats, who, from the 10th day after diabetes induction, were administered per os extracts of red and yellow fruits of the cornelian cherry and loganic acid obtained from yellow fruits at a dose of 20 mg/kg of body weight for 14 days. On the 24th day of the experiment, the rats were decapitated under ether anesthesia, and blood was taken. The content of pyruvate and lactate (as the end products of anaerobic glycolysis) and L-lactate dehydrogenase activity were determined in plasma and erythrocytes, as well as biochemical markers of the antioxidant status of erythrocytes (activity of superoxide dismutase, catalase and glutathione peroxidase, level of reduced glutathione, TBA-reactive substances, concentration of oxidative modifications of proteins and advanced oxidation protein products). Results. The activity of catalase, superoxide dismutase, glutathione peroxidase and the concentration of reduced glutathione significantly increased against the decrease in the content of oxidative modifications of proteins, advanced oxidation protein products, TBA-reactive substances, pyruvate, L-lactate, and lactate dehydrogenase in rats with DM after administration of the fruit extracts of the cornelian cherry. Noteworthy, these biochemical indicators made it possible to assess the intensity of anaerobic glycolysis and the antioxidant status of blood erythrocytes in streptozotocin diabetes. Conclusions. Extracts of Cornus mas L. fruits might be potential natural drugs for the treatment of metabolic disorders in diabetes, as they have a corrective effect on the catabolic breakdown of glucose and the antioxidant defense system of erythrocytes, preventing the development of oxidative stress. It should be pointed out that the extract of red fruits of cornelian cherry showed the best effect among the studied extracts in normalizing these indicators.

Green tea supplementation prevented oxidative stress, fibrosis, and myocardial damage in isoproterenol-induced Swiss albino mice

IntroductionOne of the main causes of death and morbidity in people with cardiovascular disorders is myocardial infarction. This study investigated the impact of green tea (GT) leaf powder on isoproterenol (ISO)-induced myocardial infarction in Swiss albino mice. Methods and materials4 to 5 weeks male Swiss albino mice were divided into four groups with 6 mice in every group: Control, ISO, Control + GT and ISO+ GT leaves powder. All of the mice were sacrificed at the end of the investigation. Heart organ and blood plasma samples were taken, and they were tested for oxidative stress indicators and several biochemical parameters. To investigate the formation of mononuclear cells and fibrosis in the heart histopathological staining of tissue sections was also carried out. ResultsIn this experiment, supplementation with green tea leaf powder in ISO-administered mice prevented the increased activity of the AST, ALT, and ALP enzymes. Additionally, three more tests were performed such as CK-MB, Creatinine, and Uric acid whose levels were increased by isoproterenol, and treatment of green tea reduced these elevated levels. Due to the supplementation of green tea leaf powder, ISO-administered mice had lower levels of lipid peroxidation product, nitric oxide, advanced protein oxidation product, and myeloperoxidase. Mice exposed to ISO had considerably higher levels of oxidative stress markers and lower levels of cellular antioxidants including catalase activity, SOD activity, and reduced glutathione concentration. Additionally, the heart of ISO-induced mice revealed substantial fibrosis and inflammatory cell infiltration. Furthermore, green tea leaf powder supplementation prevented inflammatory cell infiltration and fibrosis in ISO-administered mice. ConclusionIn conclusion, the findings imply that supplementing with green tea leaf powder might lower the risk of myocardial infarction in mice given ISO, potentially by reducing oxidative stress, inflammation, and fibrosis.

Structural characterization and bioactivities of maize bran feruloylated arabinoxylan and oligosaccharides obtained by a combined hydrothermal and enzymatic pre-treatment

Feruloylated arabinoxylans (F-AX) are gaining importance due to their immense health benefits as nutraceuticals. In the current study, we extracted F-AX from maize bran by a combination of hydrothermal pre-treatment and xylanase and cellulase double enzymatic digestion and studied them in detail. The F-AX composition included carbohydrate (533.74 ± 7.59 mg/g), and phenolic acid (153.71 ± 3.55 mg/g) with an arabinoxylan percentage of 74.17% and degree of substitution of 0.99. Ferulic acid was the major phenolic acid found esterified to arabinose. The GC, FTIR, UPLC, and methylation analysis revealed the typical structure of arabinoxylan with bound ferulic acid and a highly substituted xylopyranose backbone. The LC-MS/MS analysis revealed the structure of F-AXOS, which were the predominant oligosaccharides in the purified fraction. The F-AX showed potent antioxidant activity (DPPH, ABTS, and FRAP) and could effectively inhibit the formation of advanced glycation end products (argpyrimidine, pentosidine, and vesperlysine) and protein oxidation products (dityrosine and N′-formylkynurenine). F-AX also showed potent antiproliferative activity against the human colon cancer cells - Colo 205 and HCT 116. The current study revealed that the combined extraction method has yielded a unique blend of F-AX with bioactivities and these molecules have the potential to be used in the development of innovative functional foods.

Berberine attenuates brain aging via stabilizing redox homeostasis and inflammation in an accelerated senescence model of Wistar rats.

Aging is a multifaceted and progressive physiological change of the organism categorized by the accumulation of deteriorating processes, which ultimately compromise the biological functions. The objective of this study was to investigate the anti-aging potential of berberine (BBR) in D-galactose (D-Gal) induced aging in rat models. In this study, male Wistar rats were divided into four groups: The control group was given only vehicle, the BBR group was treated with berberine orally, the D-Gal group was treated with D-galactose subcutaneously and the BBR + D-Gal group was treated with D-galactose and berberine simultaneously. D-galactose exposure elevated the pro-oxidants such as malondialdehyde (MDA) level, protein carbonyl and advanced oxidation protein products (AOPP) in the brain. It decreased the anti-oxidants such as reduced glutathione (GSH) and ferric reducing antioxidant potential (FRAP) in the brain. D-galactose treatment also reduced the mitochondrial complexes (I, II, III and IV) activities and elevated the inflammatory markers such as interleukine-6 (IL-6), tumor necrosis factor- α (TNF-α) and C-reactive protein (CRP). The mRNA expressions of IL-6 and TNF-α in the brain were upregulated following D-galactose exposure. Berberine co-treatment in D-galactose induced aging rat model prevented the alteration of pro-oxidant and anti-oxidant in the brain. Berberine treatment restored the mitochondrial complex activities in the brain and also normalized the inflammatory markers. Based on these findings we conclude that berberine treatment has the potential to mitigate brain aging in rats via stabilizing the redox equilibrium and neuroinflammation.

Elucidation of the Role of TRPV1, VEGF-A, TXA2, Redox Homeostasis, and Inflammatory Cascades in Protection against Cold Injuries by Herbosomal-Loaded PEG-Poloxamer Topical Formulation.

High-altitude regions, cold deserts, permafrost regions, and the polar region have some of the severest cold conditions on earth and pose immense perils of cold injuries to exposed individuals. Accidental and unintended exposures to severe cold, either unintentionally or due to occupational risks, can greatly increase the risk of serious conditions including hypothermia, trench foot, and cold injuries like frostbite. Cold-induced vasoconstriction and intracellular/intravascular ice crystal formation lead to hypoxic conditions at the cellular level. The condition is exacerbated in individuals having inadequate and proper covering and layering, particularly when large area of the body are exposed to extremely cold environments. There is a paucity of preventive and therapeutic pharmacological modalities that have been explored for managing and treating cold injuries. Given this, an efficient modality that can potentiate the healing of frostbite was investigated by studying various complex pathophysiological changes that occur during severe cold injuries. In the current research, we report the effectiveness and healing properties of a standardized formulation, i.e., a herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF), on frostbite. The intricate mechanistic pathways modulated by the novel formulation have been elucidated by studying the pathophysiological sequelae that occur following severe cold exposures leading to frostbite. The results indicate that n-HPTF ameliorates the outcome of frostbite, as it activates positive sensory nerves widely distributed in the epidermis transient receptor potential vanilloid 1 (TRPV1), significantly (p < 0.05) upregulates cytokeratin-14, promotes angiogenesis (VEGF-A), prominently represses the expression of thromboxane formation (TXA2), and significantly (p < 0.05) restores levels of enzymatic (glutathione reductase, superoxide dismutase, and catalase) and nonenzymatic antioxidants (glutathione). Additionally, n-HPTF attenuates oxidative stress and the expression of inflammatory proteins PGF-2α, NFκB-p65, TNF-α, IL-6, IL-1β, malondialdehyde (MDA), advanced oxidative protein products (AOPP), and protein carbonylation (PCO). Masson's Trichrome staining showed that n-HPTF stimulates cellular proliferation, and increases collagen fiber deposition, which significantly (p < 0.05) promotes the healing of frostbitten tissue, as compared to control. We conclude that protection against severe cold injuries by n-HPTF is mediated via modulation of pathways involving TRPV1, VEGF-A, TXA2, redox homeostasis, and inflammatory cascades. The study is likely to have widespread implications for the prophylaxis and management of moderate-to-severe frostbite conditions.

Shedding light on the shadows: oxidative stress and its pivotal role in prostate cancer progression.

Data on oxidative protein damage, total antioxidant capacity (TAC) and lipid peroxidation in progression of prostate cancer remain elusive. So far, the influence of the presence of perineural invasion on the level of oxidative stress has not been described. Additionally, there is limited data on the level of oxidative stress in patients' urine. We compared the levels of oxidative stress markers in serum and urine in 50 patients with prostate cancer depending on the tumor stage and histological grade, the Gleason score, and the presence of perineural invasion. We found a significantly de-creased level of serum thiol groups and TAC in participants with prostate cancer. Similarly, serum Amadori products and malondialdehyde (MDA) were higher in patients than in healthy men. There was a significantly decrease in TAC and a significantly increased MDA in the urine of prostate cancer patients. As the stage of cancer increased, a decrease in the thiol group concentration and TAC as well as an increase in the concentration of lipid peroxidation products in the serum was observed. The serum level of advanced oxidation protein products (AOPP) increased in the group with Gleason scores greater than 7. Furthermore, serum thiol groups and TAC were reduced in the group with Gleason >7 as compared to Gleason <7. The presence of perineural invasion significantly reduced serum and urinary TAC and increased urinary AOPP concentration. These results indicate a significant role for oxidative damage in prostate carcinogenesis and its progression. Characterizing oxidative and nitrosative damage to proteins may be useful in designing targeted therapies for prostate cancer patients.

Naringenin mitigates aluminum toxicity-induced learning memory impairments and neurodegeneration through amelioration of oxidative stress.

Aluminum chloride (AlCl3) is a potent neurotoxic substance known to cause memory impairment and oxidative stress-dependent neurodegeneration. Naringenin (NAR) is a dietary flavonoid with potent antioxidant and anti-inflammatory properties which was implemented against AlCl3-induced neurotoxicity to ascertain its neuroprotective efficacy. Experimental neurotoxicity in mice was induced by exposure of AlCl3 (10 mg/kg, p.o.) followed by treatment with NAR (10 mg/kg, p.o.) for a total of 63 days. Assessed the morphometric, learning memory dysfunction (novel object recognition, T- and Y-maze tests), neuronal oxidative stress, and histopathological alteration in different regions of the brain, mainly cortex, hippocampus, thalamus, and cerebellum. AlCl3 significantly suppressed the spatial learning and memory power which were notably improved by administration of NAR. The levels of oxidative stress parameters nitric oxide, advanced oxidation of protein products, protein carbonylation, lipid peroxidation, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and the activity of acetylcholine esterase were altered 1.5-3 folds by AlCl3 significantly. Treatment of NAR remarkably restored the level of oxidative stress parameters and maintained the antioxidant defense system. AlCl3 suppressed the expression of neuronal proliferation marker NeuN that was restored by NAR treatment which may be a plausible mechanism. NAR showed therapeutic efficacy as a natural supplement against aluminum-intoxicated memory impairments and histopathological alteration through a mechanism involving an antioxidant defense system and neuronal proliferation.

Advanced oxidation protein products and catalase activity in patients with psoriasis

Advanced oxidation protein products and catalase activity in patients with psoriasis

A chronic intermittent haemodialysis pig model for functional evaluation of dialysis membranes.

Performance evaluation of new dialysis membranes is primarily performed in vitro, which can lead to differences in clinical results. Currently, data on dialysis membrane performance and safety are available only for haemodialysis patients. Herein, we aimed to establish an in vivo animal model of dialysis that could be extrapolated to humans. We created a bilateral nephrectomy pig model of renal failure, which placed a double-lumen catheter with the hub exposed dorsally. Haemodialysis was performed in the same manner as in humans, during which clinically relevant physiologic data were evaluated. Next, to evaluate the utility of this model, the biocompatibility of two kinds of membranes coated with or without vitamin E used in haemodiafiltration therapy were compared. Haemodialysis treatment was successfully performed in nephrectomized pigs under the same dialysis conditions (4 h per session, every other day, for 2 weeks). In accordance with human clinical data, regular dialysis alleviated renal failure in pigs. The vitamin E-coated membrane showed a significant reduction rate of advanced oxidation protein products during dialysis than non-coated membrane. In conclusion, this model mimics the pathophysiology and dialysis condition of patients undergoing haemodialysis. This dialysis treatment model of renal failure will be useful for evaluating the performance and safety of dialysis membranes.

THE IMPACT OF EDARAVONE ON THE MARKERS OF CARBONYL-OXIDATIVE STRESS IN RATS WITH TRAUMATIC BRAIN INJURY

In the condition of traumatic brain injury (TBI), the brain develops a series of complex metabolic changes, including protein carbonylation, enhanced lipid peroxidation, impaired neurotransmitter release, and imbalanced energy supply, that are associated with the development of different functional disorders so the search for preventive medications in this pathology is very important. Edaravone is considered a supplementary drug in the treatment of different functional disorders of the central nervous system, but the mechanisms of its protective action remain under question. Aim. This comparative research aimed to study the effects of edaravone on the biomarkers of carbonyl-oxidative stress (COS) in rats with traumatic brain injury. TBI was caused by mechanical damage with a metal weight (450 g) falling from a height of 170 cm. Methods. Advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances, protein carbonyls (PC370/PC430) were studied using spectrophotometry in serum and fraction S1 in brain cortex and hippocampus of experimental animals. Edaravone supplementation may provide significant protection against brain hemorrhagic complications by reducing COS and oxidative modification of proteins. Resylts. In our study, edaravone demonstrated moderate efficacy in reducing serum PC430 and AOPP levels, indicating its ability to attenuate TBI-induced oxidative damage. In addition to its systemic effects, edaravone exerted targeted effects on COS-modified proteins in the hippocampus, even though such biomarkers were not altered significantly by TBI alone. Concluson. Further research is necessary to elucidate the primary mechanisms of action of this drug based on the data obtained.

Changes in biomarkers of the redox status in whole blood and red blood cell lysates in canine hypothyroidism

Hypothyroidism is the most commonly diagnosed endocrine disease in dogs. The objective of this study was to evaluate the changes in the redox status in canine hypothyroidism using whole blood (WB) and red blood cell (RBCs) lysates. For this purpose, a panel of five antioxidants and five oxidants biomarkers was measured in WB and RBCs lysates of 30 dogs with hypothyroidism, 26 dogs with non-thyroidal illnesses and 15 healthy dogs. The antioxidants measured were cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC), thiol and paraoxonase type-1 (PON-1). Oxidants measured include the total oxidant status (TOS), peroxide-activity (POX-Act), reactive oxygen-derived metabolites (d-ROMs), advanced oxidation protein products (AOPP) and thiobarbituric acid reactive substances (TBARS). WB showed a significant decrease of the antioxidants CUPRAC, TEAC and thiol, and also an increase in TBARS and a decrease in AOPP in dogs with hypothyroidism compared to healthy dogs. Meanwhile, RBCs lysates showed a significant increase in FRAP and PON-1 in dogs with hypothyroidism. The changes in the redox biomarkers in this study show that WB in canine hypothyroidism had a higher number of changes in biomarkers of the redox status than RBCs lysates, making it a promising sample type for the evaluation of the redox status in this disease. In addition, WB is easier and simpler to process than RBCs lysates and unlike serum, it does not have any hemolysis interference.

Inclusion of reeling wastewater-derived sericin peptides in high-protein nutrition bars for antihardening and storage stability

The utilization of agroindustrial wastes to enrich food protein resources and the exploration of their broader applications are crucial for addressing the food crisis and achieving sustainable development goals. In this study, reeling wastewater-derived sericin was hydrolyzed using papain and trypsin to prepare sericin peptide (SRP) and was used as an antihardening ingredient of high-protein nutrition bars (HPNBs). The mechanism of the antihardening effect of SRP was elucidated by investigating the content of advanced glycation end products and protein oxidation products (carbonyl and free sulfhydryl), and the molecular weight change of HPNBs during storage before and after the addition of SRP. Our results confirmed the fortification of HPNBs with SRP, which is beneficial for the promotion and expansion of sericin applications in the food industry, with positive implications for the rational utilization of protein resources and the enrichment of food protein sources.

Moringa oleifera-based feed supplement protects against renal ischaemia/reperfusion injury via downregulation of Bax/caspase 3 signaling.

Ischaemia/reperfusion (I/R) may lead to acute kidney injury via the induction of oxidative stress. On the other hand, Moringa oleifera has been reported to exert antioxidant activities. This study was designed to assess whether or not Moringa oleifera-based feed supplement could prevent I/R-induced renal injury. Renal I/R was induced by occluding the right renal artery for 30 min followed by a 2-h reperfusion. Renal I/R led to increased absolute renal weight and renal organo-somatic weight index. Renal I/R also caused distortion of renal histoarchitecture and impaired renal function evidenced by elevated serum creatinine and blood urea nitrogen. In addition, renal I/R significantly elevated renal levels of hydrogen peroxide, MDA, and advanced oxidation protein products, but suppressed the levels of reduced glutathione, protein thiol, and non-protein thiol, and the activities of superoxide dismutase and glutathione peroxidase. In addition, renal I/R up-regulated myeloperoxidase activity and the renal levels of NO, TNF-α, and IL-6. Renal I/R also up-regulated Bax and caspase 3 expression in the kidney. Furthermore, I/R-driven structural and biochemical alterations were markedly inhibited by Moringa oleifera-based feed supplement. These results suggest that Moringa oleifera-based feed supplement may preserve the gross and histoarchitectural integrity of the kidney as well as renal function via downregulation of Bax/caspase 3 signaling by targeting oxidative stress, inflammation and apoptosis in the kidney of I/R rat.

Combined effect of pantoprazole and mesenchymal stem cells on experimentally induced gastric ulcer: implication of oxidative stress, inflammation and apoptosis pathways

Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.

In Vivo Evaluation of Innovative Gadolinium-Based Contrast Agents Designed for Bioimaging Applications.

The aim of this study was the investigation of biochemical and histological changes induced in different tissues, as a result of the subcutaneous administration of Gd nanohydrogels (GdDOTA⸦CS-TPP/HA) in a CD-1 mouse strain. The nanohydrogels were obtained by encapsulating contrast agents (GdDOTA) in a biocompatible polymer matrix composed of chitosan (CS) and hyaluronic acid (HA) through the ionic gelation process. The effects of Gd nanohydrogels on the redox status were evaluated by measuring specific activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as oxidative stress markers, such as reduced glutathione (GSH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), and protein-reactive carbonyl groups (PRCG), in the liver, kidney, and heart tissues. The nitrosylated proteins expression were analyzed with Western Blot and the serum biochemical markers were measured with spectrophotometric methods. Also, a histological analysis of CD-1 mouse tissues was investigated. These results indicated that Gd nanohydrogels could potentially be an alternative to current MRI contrast agents thanks to their low toxicity in vivo.