Apigenin Provides Structural Protection to Human Fibrinogen against Nitrosative Stress: Biochemical and Molecular Insights.

BACKGROUND: Peroxynitrite (ONOO-) is an oxidant linked with several human pathologies. Apigenin, a natural flavonoid known for its health benefits, remains unexplored in relation to ONOO- effects. This study investigated the potential of apigenin to structurally protect fibrinogen, an essential blood clotting factor, from ONOO--induced damage. METHODS: Multi-approach analyses were carried out where fibrinogen was exposed to ONOO- generation while testing the efficacy of apigenin. The role of apigenin against ONOO--induced modifications in fibrinogen was investigated using UV spectroscopy, tryptophan or tyrosine fluorescence, protein hydrophobicity, carbonylation, and electrophoretic analyses. RESULTS: The findings demonstrate that apigenin significantly inhibits ONOO--induced oxidative damage in fibrinogen. ONOO- caused reduced UV absorption, which was reversed by apigenin treatment. Moreover, ONOO- diminished tryptophan and tyrosine fluorescence, which was effectively restored by apigenin treatment. Apigenin also reduced the hydrophobicity of ONOO--damaged fibrinogen. Moreover, apigenin exhibited protective effects against ONOO--induced protein carbonylation. SDS-PAGE analyses revealed that ONOO-treatment eliminated bands corresponding to fibrinogen polypeptide chains Aα and γ, while apigenin preserved these changes. CONCLUSIONS: This study highlights, for the first time, the role of apigenin in structural protection of human fibrinogen against peroxynitrite-induced nitrosative damage. Our data indicate that apigenin offers structural protection to all three polypeptide chains (Aα, Bß, and γ) of human fibrinogen. Specifically, apigenin prevents the dislocation or breakdown of the amino acids tryptophan, tyrosine, lysine, arginine, proline, and threonine and also prevents the exposure of hydrophobic sites in fibrinogen induced by ONOO-.

Role of reactive carbonyls and superoxide radicals in protein damage by cigarette smoke extracts: Comparison of Heat-not-Burn e-cigarettes to conventional cigarettes.

Oxidative protein damage involving carbonylation of respiratory tract proteins typically accompanies exposure to tobacco smoke. Such damage can arise via multiple mechanisms, including direct amino acid oxidation by reactive oxygen species or protein adduction by electrophilic aldehydes. This study investigated the relative importance of these pathways during exposure of a model protein to fresh cigarette emission extracts. Briefly, protein carbonyl adducts were estimated in bovine serum albumin following incubation in buffered solutions with whole cigarette emissions extracts prepared from either a single 1R6F research cigarette or a single "Heat-not-Burn" e-cigarette. Although both extracts caused concentration-dependent protein carbonylation, conventional cigarette extracts produced higher adduct yields than e-cigarette extracts. Superoxide radical generation by conventional and e-cigarette emissions was assessed by monitoring nitro blue tetrazolium reduction and was considerably lower in extracts made from "Heat-Not-Burn" e-cigarettes. The superoxide dismutase/catalase mimic EUK-134 strongly suppressed radical production by whole smoke extracts from conventional cigarettes, however, it did not diminish protein carbonyl adduction when incubating smoke extracts with the model protein. In contrast, edaravone, a neuroprotective drug with strong carbonyl-trapping properties, strongly suppressed protein damage without inhibiting superoxide formation. Although these findings require extension to appropriate cell-based and in vivo systems, they suggest reactive aldehydes in tobacco smoke make greater contributions to oxidative protein damage than smoke phase radicals.

Effects of a Curcumin/Silymarin/Yeast-Based Mycotoxin Detoxifier on Redox Status and Growth Performance of Weaned Piglets under Field Conditions.

The aim of this in vivo study was to investigate the effects of a novel mycotoxin detoxifier whose formulation includes clay (bentonite and sepiolite), phytogenic feed additives (curcumin and silymarin) and postbiotics (yeast products) on the health, performance and redox status of weaned piglets under the dietary challenge of fumonisins (FUMs). The study was conducted in duplicate in the course of two independent trials on two different farms. One hundred and fifty (150) weaned piglets per trial farm were allocated into two separate groups: (a) T1 (control group): 75 weaned piglets received FUM-contaminated feed and (b) T2 (experimental group): 75 weaned piglets received FUM-contaminated feed with the mycotoxin-detoxifying agent from the day of weaning (28 days) until 70 days of age. Thiobarbituric acid reactive substances (TBARSs), protein carbonyls (CARBs) and the overall antioxidant capacity (TAC) were assessed in plasma as indicators of redox status at 45 and 70 days of age. Furthermore, mortality and performance parameters were recorded at 28, 45 and 70 days of age, while histopathological examination was performed at the end of the trial period (day 70). The results of the present study reveal the beneficial effects of supplementing a novel mycotoxin detoxifier in the diets of weaners, including improved redox status, potential hepatoprotective properties and enhanced growth performance.

Acarbose Mitigates Age-Dependent Alterations in Erythrocyte Membrane Transporters During Aging in Rats.

Acarbose (ACA), a well-studied and effective inhibitor of α-amylase and α-glucosidase, is a postprandial-acting antidiabetic medicine. The membrane of the erythrocyte is an excellent tool for analyzing different physiological and biochemical activities since it experiences a range of metabolic alterations throughout aging. It is uncertain if ACA modulates erythrocyte membrane activities in an age-dependent manner. As a result, the current study was conducted to explore the influence of ACA on age-dependent deteriorated functions of transporters/exchangers, disrupted levels of various biomarkers such as lipid hydroperoxides (LHs), protein carbonyl (PCO), sialic acid (SA), total thiol (-SH), and erythrocyte membrane osmotic fragility. In addition to a concurrent increase in Na+/H+ exchanger activity and concentration of LH, PCO, and osmotic fragility, we also detected a considerable decrease in membrane-linked activities of Ca2+-ATPase (PMCA) and Na+/K+-ATPase (NKA), as well as concentrations of SA and -SH in old-aged rats. The aging-induced impairment of the activities of membrane-bound ATPases and the changed levels of redox biomarkers were shown to be effectively restored by ACA treatment.

Brain damage induced by contaminants released in a hospital from Mexico: Evaluation of swimming behavior, oxidative stress, and acetylcholinesterase in zebrafish (Danio rerio).

Several studies have indicated that hospital effluents can produce genotoxic and mutagenic effects, cytotoxicity, hematological and histological alterations, embryotoxicity, and oxidative stress in diverse water organisms, but research on the neurotoxic effects hospital wastewater materials can generate in fish is still scarce. To fill the above-described knowledge gap, this study aimed to determine whether the exposure of adult zebrafish (Danio rerio) to several proportions (0.1%, 2.5%, 3.5%) of a hospital effluent can disrupt behavior or impair redox status and acetylcholinesterase content in the brain. After 96 h of exposure to the effluent, we observed a decrease in total distance traveled and an increase in frozen time compared to the control group. Moreover, we also observed a significant increase in the levels of reactive oxygen species in the brains of the fish, especially in hydroperoxide and protein carbonyl content, relative to the control group. Our results also demonstrated that hospital effluents significantly inhibited the activity of the AChE enzyme in the brains of the fish. Our Pearson correlation demonstrated that the response to acetylcholinesterase at the lowest proportions (0.1% and 2.5%) is positively related to the oxidative stress response and the behavioral changes observed. The cohort of our studies demonstrated that the exposure of adult zebrafish to a hospital effluent induced oxidative stress and decreased acetylcholinesterase activity in the brain of these freshwater organisms, which can lead to alterations in their behavior.

Protective effects of chrysin against the neurotoxicity induced by aluminium: In vitro and in vivo studies.

Chronic exposure to aluminium (Al) can contribute to the progression of several neurological and neurodegenerative diseases. Al is a metal that promotes oxidative damage leading to neuronal death in different brain regions with behavior, cognition, and memory deficits. Chrysin is a flavonoid found mainly in honey, passion fruit, and propolis with antioxidant, anti-inflammatory, and cytoprotective properties. In this study, we used an integrated approach of in vitro and in vivo studies to evaluate the antioxidant and neuroprotective effects of chrysin against the neurotoxicity elicited by aluminium chloride (AlCl3). In in vitro studies, chrysin (5 µM) showed the ability to counteract the early oxidative stress elicited by tert-butyl hydroperoxide, an oxidant that mimics the lipid peroxidation and Fenton reaction in presence of AlCl3 as well as the late necrotic death triggered by AlCl3 in neuronal SH-SY5Y cells. In vivo studies in a mouse model of neurotoxicity induced by chronic exposure to AlCl3 (100 mg/kg/day) for ninety days then corroborated the antioxidant and neuroprotective effect of chrysin (10, 30, and 100 mg/kg/day) using the oral route. In particular, chrysin reduced the cognitive impairment induced by AlCl3 as well as normalized the acetylcholinesterase and butyrylcholinesterase activities in the hippocampus. In parallel, chrysin counteracted the oxidative damage, in terms of lipid peroxidation, protein carbonylation, catalase, and superoxide dismutase impairment, in the brain cortex and hippocampus. Lastly, necrotic cells frequency in the same brain regions was also decreased by chrysin. These results highlight the ability of chrysin to prevent the neurotoxic effects associated with chronic exposure to Al and suggest its potential use as a food supplement for brain health.

Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis.

Cardiovascular diseases (CVD) are a leading cause of mortality worldwide, and dietary habits represent a major risk factor for dyslipidemia; a hallmark of CVD. Saturated fatty acids contribute to CVD by aggravating dyslipidemia, and, in particular, lauric acid (LA) raises circulating cholesterol levels. The role of red blood cells (RBCs) in CVD is increasingly being appreciated, and eryptosis has recently been identified as a novel mechanism in CVD. However, the effect of LA on RBC physiology has not been thoroughly investigated. RBCs were isolated from heparin-anticoagulated whole blood (WB) and exposed to 50-250 µM of LA for 24 h at 37 °C. Hemoglobin was photometrically examined as an indicator of hemolysis, whereas eryptosis was assessed by Annexin V-FITC for phosphatidylserine (PS) exposure, Fluo4/AM for Ca2+, light scatter for cellular morphology, H2DCFDA for oxidative stress, and BODIPY 581/591 C11 for lipid peroxidation. WB was also examined for RBC, leukocyte, and platelet viability and indices. LA caused dose-responsive hemolysis, and Ca2+-dependent PS exposure, elevated erythrocyte sedimentation rate (ESR), cytosolic Ca2+ overload, cell shrinkage and granularity, oxidative stress, accumulation of lipid peroxides, and stimulation of casein kinase 1α (CK1α). In WB, LA disrupted leukocyte distribution with elevated neutrophil-lymphocyte ratio (NLR) due to selective toxicity to lymphocytes. In conclusion, this report provides the first evidence of the pro-eryptotic potential of LA and associated mechanisms, which informs dietary interventions aimed at CVD prevention and management.

Dietary Antioxidant Capacity Promotes a Protective Effect against Exacerbated Oxidative Stress in Women Undergoing Adjuvant Treatment for Breast Cancer in a Prospective Study.

Breast cancer (Bca) is the most common type of cancer among women worldwide, and oxidative stress caused by adjuvant treatment may be decreased by antioxidant intake. The aim of this study is to investigate the associations between Dietary antioxidant Capacity (DaC) and oxidation and antioxidant biomarkers in women undergoing adjuvant treatment (AT) for Bca. This prospective study had a sample of 70 women (52.2 ± 10.7 y). DaC (mmol/g) was calculated using nutritional data obtained from a Food Frequency Questionnaire, and blood was collected to measure the oxidation and antioxidant biomarkers at baseline (T0), and after AT (T1). Carbonylated protein levels were inversely associated with DaC at T1 (p = 0.004); women showed an increased risk of having increment on lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS), and decrement on ferric reducing antioxidant power (FRAP) and reduced glutathione after AT, in response to lowered DaC (p < 0.05). Carbonylated proteins, TBARS and FRAP levels remained stable between the periods for women at the 3rd DaC tertile at T1, differentiating them from those at the 1st tertile, who showed negative changes in these biomarkers (p < 0.04). DaC may be beneficial for women undergoing AT for Bca, since it promoted a reduction in oxidative stress.

Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-ß-boswellic acid isolated from Boswellia serrata.

Malaria eradication is still a major global health problem in developing countries, which has been of more concern ever since the malaria parasite has developed resistance against frontline antimalarial drugs. Historical evidence proves that the plants possess a major resource for the development of novel anti-malarial drugs. In the present study, the bioactivity guided fractionation of the oleogum-resin of Boswellia serrata Roxb. yielded the optimum activity in the ethyl acetate fraction with an IC50 of 22 ± 3.9 µg/mL and 26.5 ± 4.5 µg/mL against chloroquine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum respectively. Further, upon fractionation, the ethyl acetate fraction yielded four major compounds, of which 3-Hydroxy-11-keto-ß-boswellic acid (KBA) was found to be the most potent with IC50 values 4.5 ± 0.60 µg/mL and 6.25 ± 1.02 µg/mL against sensitive and resistant strains respectively. KBA was found to inhibit heme detoxification pathways, one of the most common therapeutic targets, which probably lead to an increase in reactive oxygen species (ROS) and nitric oxide (NO) detrimental to P. falciparum. Further, the induced intracellular oxidative stress affected the macromolecules in terms of DNA damage, increased lipid peroxidation, protein carbonylation as well as loss of mitochondrial membrane potential. However, it did not exhibit any cytotoxic effect in VERO cells. Under in vivo conditions, KBA exhibited a significant reduction in parasitemia, retarding the development of anaemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis (chloroquine-resistant) infected mice. Further, KBA did not exhibit any abnormality in serum biochemistry of animals that underwent acute oral toxicity studies at 2000 mg/kg body weight.

Chrysin attenuates sodium arsenite-induced nephrotoxicity in rats by suppressing oxidative stress and inflammation.

BACKGROUND: We aimed to study the beneficial property of chrysin (CHR) by targeting its antioxidant and anti-inflammatory effects on nephrotoxicity induced by sodium arsenite (SA). MATERIALS & METHODS: We have used the 35 male Wistar rats in five equal groups (n = 7). Normal saline in (5 ml/kg; p.o.; 21 days) was given to the control group. Sodium arsenite (10 mg/kg; p.o.; 14 days) was given to the SA group. CHR (25, 50 and 100 mg/kg; p.o.; 21 days) and SA (10 mg/kg; p.o.; 14 days from the 7th day of the experiment) was given to the SA + CHR 25, 50 and 100 groups. On the 22nd day of the experiment, the animals' bloods and kidneys were taken, and then we have performed functional, biochemical and histological assessment. RESULTS: CHR pre- and alongside administration (more potently at dose of 100 mg/kg) with SA reduced the SA-induced alterations in serum creatinine and blood urine nitrogen levels. Increased levels of protein carbonyl, myeloperoxidase, malondialdehyde and nitric oxide in kidney tissue were decreased by CHR treatment. CHR administration increased the levels of glutathione and activities of glutathione peroxidase, catalase and superoxide dismutase in renal tissue. Moreover, treatment with CHR reduced the levels of inflammatory mediators including interleukin 1 beta and tumor necrosis factor alpha in renal tissue. The renal histological lesions induced SA were mitigated by CHR treatment in dose dependent manner. CONCLUSION: The results of present study suggested that administration of CHR before and alongside with SA attenuated the renal toxic effects of SA via antioxidative stress and anti-inflammatory effects.

Antioxidant properties of red raspberry extract alleviate hepatic fibrosis via inducing apoptosis and transdifferentiation of activated hepatic stellate cells.

Hepatic fibrosis is a wound-healing process caused by prolonged liver damage and often occurs due to hepatic stellate cell activation in response to reactive oxygen species (ROS). Red raspberry has been found to attenuate oxidative stress, mainly because it is rich in bioactive components. In the current study, we investigated the inhibitory effects and associated molecular mechanisms of red raspberry extract (RBE) upon activated hepatic stellate cell (aHSC) in cellular and rat models. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased in the dimethylnitrosamine (DMN)-applied samples, whereas treatment of RBE significantly suppressed the activities of these enzymes. In addition, a histopathological analysis demonstrated that RBE could substantially diminish the hepatic collagen content and alpha-smooth muscle actin (α-SMA) expression induced by DMN. Administration of 250 µg/mL RBE could also arrest the growth and enhance the apoptosis of activated HSC-T6 cells, which was accompanied with elevated levels of activated caspases and poly (ADP-ribose) polymerase (PARP) cleavage. Particularly, RBE application remarkably abolished oxidative damage within the cells and reduced the carbonylation of proteins, which was attributed to the upregulation of catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Moreover, the knockdown of Nrf2 together with the RBE treatment synergistically abrogated the expression of α-SMA and promoted the level of peroxisome proliferator-activated receptor gamma (PPAR-γ), suggesting that RBE could mitigate the transdifferentiation of HSC in a Nrf2-independent manner. These findings implied that the application of RBE could effectively remove oxidative stress and relieve the activation of HSC via modulating the caspase/PARP, Nrf2/HO-1 and PPAR-γ pathways, which may allow the development of novel therapeutic strategies against chemical-caused liver fibrogenesis.

Glycyrrhizic Acid Scavenges Reactive Carbonyl Species and Attenuates Glycation-Induced Multiple Protein Modification: An In Vitro and In Silico Study.

The current study is aimed at studying the inhibitory effect of glycyrrhizic acid (GA) on D-ribose-mediated protein glycation via various physicochemical analyses and in silico approaches. Being a potent free radical scavenger and a triterpenoid saponin, GA plays a vital role in diminishing the oxidative stress and thus could be an effective inhibitor of the nonenzymatic glycation process. Our data showed that varying concentrations of GA inhibited the in vitro BSA-AGEs via inhibiting the formation of fructosamines, fluorescent AGEs, scavenging protein carbonyl and hydroxymethyl furfural (HMF) content, and protection against D-ribose-induced modification of BSA as evident by increased free Arg and Lys residues in GA-treated Gly-BSA samples. Moreover, GA also attenuated D-ribose-induced alterations in the secondary structure of BSA by protecting the α-helix and ß-sheet conformers and amide-I band delocalization. In addition, GA attenuated the modification in ß-cross amyloid structures of BSA and in silico molecular interaction study too showed strong binding of GA with higher number of Lys and Arg residues of BSA and binding energy (ΔG) of -8.8 Kcal/mol, when compared either to reference standard aminoguanidine (AG)-BSA complex (ΔG: -4.3 Kcal/mol) or D-ribose-BSA complex (ΔG: -5.2 Kcal/mol). Therefore, GA could be a new and favorable inhibitor of the nonenzymatic glycation process that ameliorates AGEs-related complications via attenuating the AGE formation and glycation-induced multiple protein modifications with a reduced risk of adverse effects on protein structure and functionality; hence, it could be investigated at further preclinical settings for the treatment and management of diabetes and age-associated complications.

Liposome Extract of Stachys pilifera Benth Effectively Improved Liver Damage due to Bile Duct Ligation Rats.

Herbal medicines harbor essential therapeutic agents for the treatment of cholestasis. In this study, we have assessed the anticholestatic potential of Stachys pilifera Benth's (SPB's) hydroalcoholic extract encapsulated into liposomes using bile duct ligation- (BDL-) induced hepatic cholestasis in rats. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), total thiol (T-SH) content, protein carbonyl (PCO), total bilirubin (TBIL), albumin (ALB), and nitric oxide (NO) metabolite levels were measured in either liver tissue or plasma to assess liver damage. Moreover, expression of proinflammatory cytokines (IL-1ß and TNF-α) and liver fibrosis markers (TGF-ß and SM-α) which are driving forces of many liver disorders was also determined. The activity of AST, ALT, and ALP was significantly enhanced in the BDL group in comparison to the control group; however, treatment with liposomal (SPB) hydroalcoholic extract significantly reduced AST and ALT's activity. Increases in MDA, TBIL, and NO levels and T-SH content due to BDL were restored to control levels by liposomal (SPB) hydroalcoholic extract treatment. Similarly, hepatic and plasma oxidative marker MDA levels, significantly enhanced by BDL, were significantly decreased by liposomal (SPB) hydroalcoholic extract treatment. Moreover, histopathological findings further demonstrated a significant decrease in hepatic damage in the liposomal (SPB) hydroalcoholic extract-treated BDL group. In addition, liposomal (SPB) hydroalcoholic extract treatment decreased the liver expression of inflammatory cytokines (IL-1ß, TNF-α) and liver fibrosis markers (TGF-ß and SM-α). Since liposomal (SPB) hydroalcoholic extract treatment alleviated the BDL-induced injury of the liver and improved the hepatic structure and function more efficiently in comparison to free SPB hydroalcoholic extract, probable liposomal (SPB) hydroalcoholic extract exhibits required potential therapeutic value in protecting the liver against BDL-caused oxidative injury.

Antioxidant and anti-inflammatory properties of gamma- oryzanol attenuates insulin resistance by increasing GLUT- 4 expression in skeletal muscle of obese animals.

BACKGROUND: Skeletal muscle is the most important organ for whole-body glucose homeostasis. However, it has been suggested that obesity-related inflammation could be involved in insulin resistance and diabetes mellitus type 2 (DM2) development due several mechanisms, among them, the reduced expression of the glucose transporter type 4 (GLUT-4). Gamma-oryzanol (γOz) is a compound present in the whole grain of rice that presents anti-inflammatory and antioxidant activities. The aim of this study was to verify if the effect antioxidant and anti-inflammatory of yOz attenuate insulin resistance in skeletal muscle of obese rats by increasing GLUT- 4 expression. METHODS: Male Wistar rats (±187 g) were initially randomly distributed into 2 experimental groups (control, n = 6, and high sugar-fat diet (HSF), n = 12) for 20 weeks. At week 20th of this study, once obesity and insulin resistance were detected in the HSF group, animals were divided to begin the treatment with γOz or continue receiving HSF for 10 more weeks. At the end it was analyzed nutritional, metabolic, inflammatory and oxidative stress parameters and GLUT-4 protein expression. RESULTS: The treatment improved insulin resistance, reduced inflammation, increased antioxidant response and GLUT-4 expression. CONCLUSION: It is possible to conclude that the antioxidant and anti-inflammatory activity of yOz attenuates insulin resistance by increasing GLUT-4 expression in skeletal muscle of obese animals.

Antioxidant compounds from Annona crassiflora fruit peel reduce lipid levels and oxidative damage and maintain the glutathione defense in hepatic tissue of Triton WR-1339-induced hyperlipidemic mice.

Dyslipidemia is a risk factor for the pathogenesis of several diseases, such as obesity, hypertension, atherosclerosis and cardiovascular diseases. In addition to interfering with serum concentrations of cholesterol and triglycerides, hyperlipidemia is involved in oxidative stress increase and reduction of the endogenous antioxidant defenses. The fruit peel of Annona crassiflora crude extract (CEAc) and its polyphenols-rich fraction (PFAc) were investigated against hypertriglyceridemia, hypercholesterolemia and hepatic oxidative stress in Triton WR-1339-induced hyperlipidemic mice. Lipid parameters in serum, feces and liver, as well as hepatic oxidative status, and enzymatic and non-enzymatic antioxidant defense systems were analyzed. Pre-treatment with CEAc for 12 days decreased hepatic triglycerides and total cholesterol, and similar to PFAc, increased the high-density lipoprotein level. There were reductions in lipid peroxidation and protein carbonylation, as well as restoration of the glutathione defense system and total thiol content in the liver of the hyperlipidemic mice treated with PFAc. The fruit peel of A. crassiflora, a promising natural source of bioactive molecules, showed a potential lipid-lowering action and hepatoprotective activities triggered by reduction of oxidative damage and maintenance of the enzymatic and non-enzymatic antioxidant systems impaired by the hyperlipidemic state.

Testicular deficiency associated with exposure to cypermethrin, imidacloprid, and chlorpyrifos in adult rats.

The testicular deficiency associated with exposure to three widely used insecticides in Egyptian agriculture was evaluated. Animals were orally treated with sub-lethal dose (1/50 of the oral LD50) of cypermethrin (CYP), imidacloprid (IMC), and chlorpyrifos (CPF) at 5, 9 and 1.9 mg/kg/day, respectively, five times a week for one month. The CYP, IMC, and CPF exposure resulted in a significant decline in animal body weight, sperm count, motility, normality, and viability with increased head and tail deformities. Significant reduction in serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testis superoxide dismutase (SOD), and reduced glutathione (GSH) levels. In contrast, catalase (CAT), lipid peroxidation (LPO), and protein carbonyl content (PCC) levels were significantly stimulated. Jointly, obtained results were confirmed by microscopic examination of testis sections. The present data concluded that the CYP, IMC, and CPF have a public health impact and violently interferes with male rat reproductive system.

The influence of salinity on sodium lauryl sulfate toxicity in Mytilus galloprovincialis.

The influence of salinity on the effects of sodium lauryl sulfate (SLS) was evaluated using the Mediterranean mussel Mytilus galloprovincialis, exposed for 28 days to SLS (control-0.0 and 4.0 mg/L) under three salinity levels (Control-30, 25 and 35). The effects were monitored using biomarkers related to metabolism and energy reserves, defence mechanisms (antioxidant and biotransformation enzymes) and cellular damage. The results revealed that non-contaminated mussels tended to maintain their metabolic capacity regardless of salinity, without activation of antioxidant defence strategies. On the contrary, although contaminated mussels presented decreased metabolic capacity at salinities 25 and 35, they were able to activate their antioxidant mechanisms, preventing cellular damage. Overall, the present findings indicate that SLS, especially under stressful salinity levels, might potentially jeopardize population survival and reproduction success since reduced metabolism and alterations on mussels' antioxidant mechanisms will impair their biochemical and, consequently, physiological performance.

Protective Effects of Swertiamarin against Methylglyoxal-Induced Epithelial-Mesenchymal Transition by Improving Oxidative Stress in Rat Kidney Epithelial (NRK-52E) Cells.

Increased blood glucose in diabetic individuals results in the formation of advanced glycation end products (AGEs), causing various adverse effects on kidney cells, thereby leading to diabetic nephropathy (DN). In this study, the antiglycative potential of Swertiamarin (SM) isolated from the methanolic extract of E. littorale was explored. The effect of SM on protein glycation was studied by incubating bovine serum albumin with fructose at 60 °C in the presence and absence of different concentrations of swertiamarin for 24 h. For comparative analysis, metformin was also used at similar concentrations as SM. Further, to understand the role of SM in preventing DN, in vitro studies using NRK-52E cells were done by treating cells with methylglyoxal (MG) in the presence and absence of SM. SM showed better antiglycative potential as compared to metformin. In addition, SM could prevent the MG mediated pathogenesis in DN by reducing levels of argpyrimidine, oxidative stress and epithelial mesenchymal transition in kidney cells. SM also downregulated the expression of interleukin-6, tumor necrosis factor-α and interleukin-1ß. This study, for the first time, reports the antiglycative potential of SM and also provides novel insights into the molecular mechanisms by which SM prevents toxicity of MG on rat kidney cells.

Folic acid alleviates the blood brain barrier permeability and oxidative stress and prevents cognitive decline in sepsis-surviving rats.

Sepsis is a complication of an infection which imbalance the normal regulation of several organ systems, including the central nervous system (CNS). Evidence points towards inflammation and oxidative stress as major steps associated with brain dysfunction in sepsis. Thus, we investigated the folic acid (FA) effect as an important antioxidant compound on acute brain dysfunction in rats and long term cognitive impairment and survival. Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with FA (10 mg/kg after CLP) or vehicle (veh). Animals were divided into sham + veh, sham + FA, CLP + veh and CLP + FA groups. Twenty-four hours after surgery, the hippocampus and prefrontal cortex were obtained and assayed for levels of blood brain barrier (BBB) permeability, nitrite/nitrate concentration, myeloperoxidase (MPO) activity, thiobarbituric acid reactive species (TBARS) formation and protein carbonyls. Survival was performed during 10 days after surgery and memory was evaluated. FA reduced BBB permeability, MPO activity in hippocampus and pre frontal cortex in 24 h and lipid peroxidation in hippocampus and improves the survival rate after sepsis. Long term cognitive improvement was verified with FA in septic rats compared with CLP + veh. Our data demonstrates that FA reduces the memory impairment in 10 days after sepsis and mortality in part by decreasing BBB permeability and oxidative stress parameters in the brain.

Lovastatin attenuates glyoxal-induced toxicity on rat liver mitochondria.

Alpha-dicarbonyls such as glyoxal (GO) trigger mitochondrial dysfunction resulting in the development of different diabetic complications. The present study investigated the effects of lovastatin against GO-induced toxicity on rat liver mitochondria. The rat liver mitochondria (0.5 mg protein/mL) were treated with various concentrations of lovastatin (1, 5, 10 µM) at 37°C for 30 min and then exposed to GO (3 mM) at 37°C for 30 min. Oxidative stress markers including MDA, reactive oxygen species (ROS), glutathione (GSH) and protein carbonylation (PC) level were measured. Mitochondrial complex II activity and mitochondrial membrane potential (MMP) were assessed for evaluating mitochondrial function. Glyoxal significantly increased the level of ROS, PC and MDA. This effect was associated with the reduction of MMP, complex II activity and GSH content. Pre-treatment with lovastatin potentially reversed GO-induced mitochondrial toxicity. These results suggest that lovastatin have a protective effect against GO-induced toxicity in isolated rat liver mitochondria.