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Objective: The Manihot esculenta Crantz (Cassava) is a typical South American plant rich in nutrients and energetic compounds. Lately, our group has shown that non-pharmacological interventions with natural antioxidants present different neuroprotective effects on oxidative balance and memory deficits in AD-like animal models. Here, our objective was to evaluate the neuroprotective effects of Cassava leaves' extract (CAS) in an AD-like model induced by amyloid-beta (Aβ) 25-35 peptide., Methods: Male Wistar rats ( n  = 40; 60 days old) were subjected to 10 days of CAS supplementation; then, we injected 2 μL Aβ 25-35 in the hippocampus by stereotaxic surgery. Ten days later, we evaluated object recognition (OR) memory. Cassavas' total polyphenols, flavonoids, and condensed tannins content were measured, as well as hippocampal lipid peroxidation and total antioxidant capacity., Results: CAS protected against Aβ-induced OR memory deficits. In addition, Aβ promoted antioxidant capacity decrease, while CAS was able to prevent it, in addition to diminishing lipoperoxidation compared to Aβ., Discussion: We show that treatment with Cassava leaves' extract before AD induction prevents recognition memory deficits related to Aβ hippocampal injection. At least part of these effects can be related to the Cassava leaves' extract supplementation effects on diminishing lipid peroxidation and preventing a decrease in the hippocampal total antioxidant capacity in the hippocampus of AD-like animals without adverse effects. Once cassavais a plant of warm and dry ground that can adapt to growon various soil types and seems to resist several insects, our results enable Cassava to be considered asa potential preventive intervention to avoid or minimizeAD-induced memory deficits worldwide.

*1. In many countries, eggs are not refrigerated and must be stored at room temperature. The objective of this study was to explore the effects of dietary oregano oil (275 mg / kg; ORE) versus an unsupplemented control diet (CON) on laying hens on the shelf life and fatty acid profile of eggs.2. Treatments were randomly distributed into 10 pens containing 27 birds each. A total of 200 eggs were collected from both groups on the same day and were stored for either 0, 10, 21 and 35 d. At each storage time, egg yolks were analysed for fatty acid profile and lipid peroxidation.3. The main indicator of lipid peroxidation, malondialdehyde (MDA), was significantly lower in ORE eggs compared to CON eggs ( p  = 0.001). Storage time had a significant impact on MDA concentrations ( p  = 0.023), with the highest found after 35 d. Significant differences were found for individual fatty acids, saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). Palmitic acid, stearic acid, oleic acid, linoleic acid and arachidonic acid were significantly lower in ORE eggs compared to CON eggs ( p  < 0.05). Palmitoleic acid ( p  = 0.002), linolenic acid ( p  = 0.001) and docosahexaenoic acid (DHA, p  = 0.001) were significantly higher in ORE eggs.4. Storage only affected oleic, linolenic, linoleic, arachidonic and docosahexaenoic acids ( p  < 0.05). Total SFA, MUFA, n -6 and ratio of n -3 to n -6 ( n -3: n -6) PUFA were significantly higher in CON eggs ( p  < 0.05). The ratio of SFA to PUFA (SFA:PUFA, p  = 0.005) and total n -3 PUFA ( p  = 0.001) were significantly higher in ORE eggs.5. The n -3: n -6 ratio was significantly impacted by treatment ( p  = 0.021) and storage ( p  = 0.031) with no significant interaction. This ratio is important for human health indication and could lead to the development of designer eggs.

Brazilian plant biodiversity is a rich alternative source of bioactive compounds since plant-derived extracts and/or their secondary metabolites exhibit potential properties to treat several diseases. In this context, Licania rigida Benth (Chrysobalanaceae Family), a large evergreen tree distributed in Brazilian semi-arid regions, deserves attention for its widespread use in popular medicine, although its biological properties are still poorly studied. The aim of this study was to examine (1) acute and sub-chronic oral toxicity at 2000 mg/kg dose; (2) in vitro cytotoxicity at 0.1; 1; 10; 100 or 1000 µg/ml; (3) in vivo mutagenicity at 5, 10 or 20 mg/ml, and (4) potential antioxidant protective effect of L. rigida aqueous leaf extract of (AE Lr ). No marked apparent toxic and genotoxic effects were observed using in vitro and in vivo assays after in vitro treatment of Chinese hamster ovary cell line (CHO-K1) with AE Lr or in vivo exposure of Wistar rats and Drosophila melanogaster to different extract concentrations. Concerning the antioxidant effect, the extract exhibited a protective effect by decreasing lipid peroxidation as determined by malondialdehyde levels. No significant changes were observed for glutathione (GSH) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Data demonstrate the beneficial potential of AE Lr to be employed for therapeutic purposes. However, further studies are required to validate the pharmacological application of this plant extract to develop as a phytotherapeutic formulation.

Kidney damages caused by cadmium are considered to be one of the most dangerous consequences for the human body. This study aimed to investigate the protective effects of fucoxanthin supplementation on mice models subjected to cadmium-induced kidney damage. The mice treated with cadmium chloride (CdCl 2 ) were observed to have significantly reduced the cross-section area of glomeruli. Cadmium exposure has also caused the damage of the structural integrity of mitochondria and increased blood urea nitrogen (BUN), kidney injury molecule 1 (KIM1), and neutrophil gelatinase associated lipocalin (NGAL) levels. Peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) levels in cadmium-exposed mice were markedly declined. Caspase3, caspase8, and caspase9 gene expressions in association with apoptosis were dramatically elevated in renal tissues. The CdCl 2 treated mice were orally administered with 50 mg/kg Shenfukang, 10 mg/kg, 25 mg/kg, and 50 mg/kg fucoxanthin for 14 days. The results revealed that high doses of fucoxanthin administration significantly decreased BUN, KIM1, NGAL levels, increasing POD, SOD, CAT, and ascorbate APX levels. Fucoxanthin administration also promoted recovery of the renal functions, micro-structural organization, and ultra-structural organization in the renal cells. In summary, the ameliorative effects of fucoxanthin supplementation against cadmium-induced kidney damage were mediated via inhibiting oxidative stress and apoptosis, promoting the recovery of structural integrity of mitochondria.

Parkinson's disease (PD) is an age-associated, progressive, and common neurodegenerative disorder. It is characterized by dopaminergic neuron degeneration in the substantia nigra pars compacta. The involvement of oxidative stress, inflammation, and dysbiosis in PD has been confirmed and probiotics also have the ability to regulate the mentioned mechanisms. Here, we assessed probiotics supplementation effects on experimental model of PD. Thirty Male Wistar rats were divided into three groups for a 14-day treatment. It was shown that a mixture of probiotics containing Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri , and Lactobacillus fermentum could improve rotational behavior, cognitive function, lipid peroxidation, and neuronal damage in the group received probiotic supplementation compared to the other groups ( P < 0001, P < .001, and P = .026, respectively). Taken together, these findings revealed that probiotics supplementation could be an appropriate complementary treatment for PD.

Background: Consumption of nutritional supplements to optimize recovery is gaining popularity among athletes. Tomatoes contain micronutrients and various bioactive components with antioxidant properties. Many of the health benefits of tomatoes have been attributed to lycopene encouraging athletes to consume pure lycopene supplements. The aim of this study was to compare the effect of tomato powder and lycopene supplement on lipid peroxidation induced by exhaustive exercise in well-trained male athletes., Methods: Eleven well-trained male athletes participated in a randomized, double-blinded, crossover study. Each subject underwent three exhaustive exercise tests after 1-week supplementation of tomato powder (each serving contained 30 mg lycopene, 5.38 mg beta-carotene, 22.32 mg phytoene, 9.84 mg phytofluene), manufactured lycopene supplement (30 mg lycopene), or placebo. Three blood samples (baseline, post-ingestion and post-exercise) were collected to assess total anti-oxidant capacity (TAC) and variables of lipid peroxidation including malondialdehyde (MDA) and 8-isoprostane. Data were analyzed using repeated-measures of ANOVA at P < 0.05., Results: Tomato powder enhanced total antioxidant capacity (12% increase, P = 0.04). Exhaustive exercise, regardless of supplement/ placebo, elevated MDA and 8-isoprostane levels (P < 0.001). The elevation of 8-isoprostane following exhaustive exercise was lower in the tomato powder treatment compared to the placebo (9% versus 24%, p = 0.01). Furthermore, following exhaustive exercise MDA elevated to a lower extent in tomatoe powder treatment compared to the placebo (20% versus 51%, p = 0.009). However, such differences were not indicated between lycopene and placebo treatments (p > 0.05)., Conclusion: Beneficial effects of tomato powder on antioxidant capacity and exercise-induced lipid peroxidation may be brought about by a synergistic interaction of lycopene with other bioactive nutrients rather than single lycopene.

The aim of the present study was to evaluate the effects of dietary supplementation with tomato peels (TP) and rosehip meal (RM) on their phytochemicals transfer to the egg, the antioxidant profile and the markers of lipid peroxidation in stored eggs. The experiment was conducted on 42-week-old TETRA SL laying hens, which were assigned to three dietary treatments with 30 birds each: the Control group (CON) received a corn-soybean diet containing 6% flaxseed meal without any by-product addition. Groups TP and RM received Diet CON with additionally 2% TP and 2% RM, respectively. Average daily feed intake, feed conversion ratio and laying percentage were not significantly changed by the dietary treatments. Compared to the other groups, the inclusion of dietary TP led to a significant increase in egg weight ( p < 0.05) and vitamin E content in eggs ( p < 0.05). The dietary inclusion of RM generated a higher vitamin A content in eggs compared to Groups CON and TP ( p < 0.10). After 40 d of storage, in Groups CON, TP and RM the vitamin E contents of eggs deceased by 10.1%, 14.2% and 13.3%, respectively, whereas the reduction of the lutein and zeaxanthin concentration in eggs was more pronounced (by 24.8%, 21.8% and 25.5%, respectively). For the most primary as well as for secondary oxidation products, storage time had a significant influence ( p < 0.05) on the degradation process of the eggs. After 40 d of storage, the most distinct reduction in the formation rate of secondary oxidation products was observed in Group RM (by more than 30%), while the reduction for Group TP amounted from 15% to 25%, when compared with Group CON. Therefore, the results of the present study showed a significantly positive effect of RM in retarding the lipid peroxidation process during storage.

Not much information is available to substantiate the possible role of γ -aminobutyric acid (GABA) signaling in mitigating water-deficit stress in snap bean ( Phaseolus vulgaris L.) plants under semiarid conditions. Present work aims to investigate the role of exogenous GABA (foliar application; 0.5, 1 and 2 mM) in amelioration of drought stress and improvement of field performance on snap bean plants raised under two drip irrigation regimes (100% and 70% of water requirements). Water stress led to significant reduction in plant growth, leaf relative water content (RWC), cell membrane stability index (CMSI), nutrient uptake (N, P, K, Ca, Fe and Zn), pod yield and its content from protein and total soluble solids (TSS). Meanwhile, lipid peroxidation (malondialdehyde content- MDA), osmolyte content (free amino acids- FAA, proline, soluble sugars) antioxidative defense (activity of superoxide dismutase- SOD, catalase- CAT, peroxidase- POX and ascorbate peroxidase- APX) and the pod fiber content exhibited significantly increase due to water stress. Exogenous GABA application (especially at 2 mM) revealed partial normalization of the effects of drought stress in snap bean plants. GABA-induced mitigation of drought stress was manifested by improvement in growth, water status, membrane integrity, osmotic adjustment, antioxidant defense and nutrient acquisition. Furthermore, GABA application during water stress in snap bean plants resulted in improvement of field performance being manifested by increased pod yield and its quality attributes. To sum up, exogenous GABA appears to function as an effective priming molecule to alleviate drought stress in snap bean plants under semiarid conditions.

Objectives : The purpose of this study was to measure the level of lipid peroxidation and investigate the response of the glutathione system to toxic doses of ethylene glycol tetraacetate acid (EGTA), Ferrum Lek, methanol, and Depakine (valproate sodium). Methods : This study focused on analyzing the toxic effects of EGTA, Ferrum Lek and methanol on lipid peroxidation processes and glutathione levels in animals. The study involved 375 outbred adult mice, of both sexes, weighing 28-31 g, and 100 outbred rats, weighing 180-200 g. Results : After 14 days of valproate sodium/ademethionine treatment, the GR (glutathione reductase) activity in experimental animals continued to be higher than in controls. Using EGTA enhanced glutathione reductase and glutathione S transferase activities in the liver and kidney. The activity of glutathione peroxidase, however, increased only in the kidney (2.1-fold, p ≤ 0.001), while in the liver, a 31% drop was observed (p ≤ 0.05). The 15-mg and 30-mg doses of Ferrum Lek caused the liver level of thiobarbituric acid reactive substances to grow 3- and 3.5-fold, respectively (p ≤ 0.001). Conclusion : The results of the study indicate that poisoning affected practically all components of the glutathione system. The oxidative stress was likely to result from an increased generation of reactive oxygen species against the background of inhibited antioxidant protection.

Purpose: Baicalein (an anti-ferroptosis drug) was recently reported to synergistically improve the survival rate of mice following a high dose of total body irradiation with anti-apoptosis and anti-necroptosis drugs. At the same time, our group has demonstrated that ferrostatin-1, a ferroptosis inhibitor, improves the survival rate of a mouse model of hematopoietic acute radiation syndrome to 60% for 150 days ( p  < .001). These phenomena suggest that ferroptosis inhibition can mitigate radiation damage. In this study, we continued to study the mechanisms by which ferrostatin-1 alleviated radiation-induced ferroptosis and subsequent hematopoietic acute radiation syndrome., Materials and Methods: Male ICR mice (8-10 weeks old) were exposed to doses of 0, 8, or 10 Gy irradiated from a 137 Cs source. Ferrostatin-1 was intraperitoneally injected into mice 72 h post-irradiation. Bone marrow mononuclear cells (BMMCs) and peripheral blood cells were counted. The changes in iron-related parameters, lipid metabolic enzymes, lipid peroxidation repair molecules (glutathione peroxidase 4, glutathione, and coenzyme Q10), and inflammatory factors (TNF-α, IL-6, and IL-1β) were evaluated using biochemical or antibody techniques., Results: Ferrostatin-1 increased the number of red and white blood cells, lymphocytes, and monocytes in the peripheral blood after total body irradiation in mice by mitigating the ferroptosis of BMMCs. Total body irradiation induced ferroptosis in BMMCs by increasing the iron and lipid peroxidation levels and depleting the acyl-CoA synthetase long-chain family member 4 (ASCL4), lipoxygenase 15, glutathione peroxidase 4, and glutathione levels. Ferroptotic BMMCs did not release TNF-α, IL-6, or IL-1β at the early stage of radiation exposure. Ferrostatin-1 mitigated the lipid peroxidation of radiation-induced ferroptosis by attenuating increases in levels of hemosiderin and liable iron pool and decreases in levels of ASCL4 and glutathione peroxidase 4., Conclusions: The onset of total body irradiation-induced ferroptosis in BMMCs involved changes in iron, lipid metabolic enzymes, and anti-lipid peroxidation molecules. Ferrostatin-1 could be a potential radiation mitigation agent by acting on these targets.

Boron is one of the most important elements with its indisputable biological importance and widespread use. The most studied derivatives of the boron element are boric acid and its salts. In this article, we searched the effects of boric acid and its lithium salt, lithium metaborate, on enzymatic defense system, cell damage, and cell surface morphology of Saccharomyces cerevisiae BY4741 strain. It was found that while all studied concentrations of boric acid showed toxicity against the yeast, even the highest studied concentration of lithium metaborate could not effectively inhibit cell viability. In addition, we observed reverse effect of lithium metaborate depend on its concentration on yeast cell proliferation and metabolic activity. As a defense mechanism, superoxide dismutase and glutathione S-transferase activities were significantly induced in yeast cells treated with boric acid. But these inductions could not protect cells from boric acid induced lipid peroxidation. It was determined that glutathione S-transferase was the only enzyme induced after lithium metaborate treatment. Finally, we visualized the signs of features of necrotic and early apoptotic mechanisms in yeast cells treated with boric acid and lithium metaborate, respectively, which should be investigated with further studies.

We used cell-free culture filtrate of Pseudomonas aeruginosa as a reducing mediator of AgNO 3 to silvernanoparticles (AgNPs) and possibly used as a potential anticancer agent against thyroid cancer cells (TPC1). The bio-generation of AgNPs was firmly established by taking a UV spectrum at 380-500 nm wavelength. The Fourier transform spectrum analysis reveals the association of alcohol, phenol and aromatic functional groups with P. aeruginosa synthesized AgNPs ( Ps -AgNPs). By observing under transmission electron microscopy (TEM), the size and structure of the Ps -AgNPs were characterized as the size was 30-70 nm and spherical in shape. The concentration-dependent cytotoxicity of Ps -AgNPs on TPC1 cells was observed and IC50 value was calculated. The alteration of oxidative and antioxidant biomarkers in Ps-AgNPs treated cells were observed. The induced apoptosis was determined by staining the Ps -AgNPs treated cells with DCFH-DA, Rh-123 dye, Acridine Orange (AO) and ethidium bromide (EtBr). Increased level of intracellular reactive oxygen species (ROS) generation and decreased level of mitochondrial membrane potential was observed in Ps -AgNPs treated TPC1 cells. Moreover, the apoptotic morphological changes were explored, which indicates increased apoptosis by inducing cell membrane damage in Ps -AgNPs treated cells. This biogenic approach will enable an effective and significant improvement in nano-oncotherapy.

Justicia secunda Vahl is an exotic plant that is used to treat medical problems. We investigated the hepatoprotective and hematological effects of aqueous extracts of J. secunda leaves on carbon tetrachloride induced toxicity in rats. Leaf extracts were prepared using hot and cold extraction methods to obtain a hot extract of J. secunda leaves (JSHAE) and a cold extract of J. secunda leaves (JSCAE). Total phenol and flavonoid measurements and antioxidant assays were performed to determine the extract with the greater antioxidant activity. JSHAE was the more effective extract for treatment of carbon tetrachloride (CCl 4 ) induced hepatotoxicity and hepatotoxicity in rats. Silymarin was used as a standard for comparison. We found that JSHAE contained more total phenol and flavonoid than JSCAE. JSHAE exhibited significantly greater ferric reducing antioxidant power and 1,1-diphenyl-2-picryl hydrazyl and thiobarbituric acid scavenging activity than JSCAE. We also found that in vivo, 100 and 200 mg/kg JSHAE significantly reduced plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and total bilirubin levels following CCl 4 induced toxicity compared to untreated rats. JSHAE treated animals exhibited white blood cell, red blood cell, hemoglobin, hematocrit, platelet and procalcitonin levels that were comparable to control animals. Liver sections of rats treated with 200 mg/kg. JSHAE exhibited no abnormalities.

Cisplatin (CP) is an antineoplastic drug; however, owing to its nephrotoxicity, its clinical use is limited. We investigated whether vitexilactone (vitex) is a safe and effective treatment for CP induced kidney injury. We allocated Sprague-Dawley rats into six groups: control group, low dose-high dose vitex groups (40 and 80 mg/kg vitex for 6 days before administration of CP), CP group (single 6 mg/kg dose on day 6) and CP + low dose vitex-CP + high dose vitex group (40 and 80 mg/kg vitex for 6 days, and a single 6 mg/kg dose of CP on day 6. Rats were euthanized 5 days after CP treatment. After exposure to CP and/or vitex, total oxidative stress and total antioxidant status were assessed. The histology of the kidney was examined using hematoxylin and eosin, and periodic acid-Schiff. We used immunohistochemical and fluorescence staining to detect expression of caspase-3. We also measured blood urea nitrogen, uric acid and creatinine levels. Nephroprotective effects of vitex were associated with decreased serum toxicity markers and increased antioxidant activity. Vitex also reduced the expression of the apoptosis marker, caspase-3. Treatment with CP increased blood urea nitrogen, uric acid, creatinine levels and total antioxidant status, and decreased total antioxidant status compared to the control group. Use of vitex for protection from CP induced nephrotoxicity appears to be a safe and efficacious alternative for treatment of kidney injury.

We investigated the protective effect of alpha lipoic acid (ALA) against cisplatin (CIS) induced hepatotoxicity in rats. ALA is an antioxidant and anti-inflammatory agent that exhibits free radical scavenger properties and direct antioxidant effects on recycling of other cellular antioxidants. We used four equal groups of rats. The control group: saline solution (0.9%) was administered intraperitoneally (i.p.); ALA group: administered a single dose 100 mg/kg ALA i.p. for 10 days; CIS group was administered a single dose 5 mg/kg CIS i.p. on the first day of the study; CIS + ALA group was administered a single dose 5 mg/kg CIS i.p. on the first day of study, then 100 mg/kg ALA i.p. for 10 days. In the CIS group, Bax, caspase3, malondialdehyde (MDA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were increased, whereas Bcl-2, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were decreased compared to the control group. In the CIS + ALA group, Bax, caspase 3, MDA, AST and ALT levels were decreased, whereas Bcl-2, SOD, CAT and GPx levels were increased compared to the CIS group. In the CIS group we found intense perivenule sinusoid dilation, karyomegaly, pyknotic and karyolytic cells, central vein congestion, parenchymal inflammation, mild bile duct proliferation and periportal sinusoid dilation. Histological liver damage was reduced in the CIS + ALA group. ALA may useful for treating CIS induced hepatotoxicity owing to its antioxidant and anti-inflammatory effects.

Organophosphorus compounds are widely used in agriculture. Epidemiological studies propose that pesticide exposure is a risk factor for Alzheimer's disease (AD), but the mechanisms are unclear. Here, we investigated the impact of malathion exposure on the cognitive ability and the underlying mechanisms in rats. Moreover, we studied whether crocin reduced malathion-induced cognitive and memory loss in rats. Malathion (100 mg/kg) and crocin (10, 20 and 40 m/kg) were administered into the rats once a day for 14 days via i.p. Also vitamin E was used as positive control. Malathion exhibited spatial memory deficits as assessed by Morris water maze (MWM). Malathion increased the latency to reach the platform and decreased time spent and swimming distance of animals in target quadrant in probe trial. These effects were protected by crocin. Malathion exposure induced spatial learning and memory deficits with a simultaneous decrease of PSD93 and TAU hyperphosphorylation at multiple AD-related phosphorylation sites with activation of glycogen synthase kinase-3β (GSK-3β) and inhibition of protein phosphatase-2A (PP2A). Additionally, the elevation of malondialdehyde (MDA), TNF α and IL-6 levels, amelioration of reduced glutathione (GSH) in the hippocampus and reduction of plasma acetylcholinesterase activity were observed upon administration of the malathion. Also, malathion-induced apoptosis in the hippocampus. Crocin or vitamin E improved memory damages and antagonized the effects of malathion. According to the data of this study, crocin mitigated malathion-induced neurological alterations and cognitive impairment by reducing oxidative stress and inflammation, inhibiting TAU protein hyperphosphorylation and antiapoptotic effects.

Protein hydrolysates usually possess higher nutritive value than an equivalent mixture of free amino acids. This study was aimed at determining the antioxidant activities of protein hydrolysates of Treculia africana seeds. Soluble protein was isolated from Treculia africana seed flour by alkaline solubilization and acid precipitation, and further hydrolyzed with three proteases (trypsin, pancreatin and pepsin) individually and in a sequential two- and three-protease systems. Antioxidant activities (DPPH, FRAP and lipid peroxidation) of the hydrolysates were investigated. Hydrolysates from Treculia africana seed protein showed varying degree of hydrolysis, pancreatin hydrolysates had the highest (94.92%) and pancreatin-pepsin hydrolysates had the least (6.59%). Pancreatin proved to be the most efficient protease for hydrolyzing Treculia africana protein with a high protein recovery of 156.06 mg/ml. Its hydrolysates exhibited the highest DPPH scavenging activity (71.02%) and had a high radical-mediated peroxidation of oleic acid. Likewise, pancreatin hydrolysates as well as trypsin-pancreatin hydrolysates showed the highest FRAP activity (37.17 and 38.52 µg/ml BHA, respectively). Pancreatin hydrolysates showed significant higher ( p <  0.05) antioxidant potentials than other hydrolysates of T. africana seed protein. These findings showed the potential use of Treculia africana hydrolysates as antioxidants in reducing food spoilage and management of oxidative stress-related metabolic disorders.

The industrialization of the agricultural sector has significantly increased the use of chemicals such as pesticides. Therefore, exposure to them is unavoidable, which makes it necessary to assess their safety for humans at actual exposure doses. This paper aims to determine toxicity of three types of pesticides toward human immune cells (HL-60 and U-937): glyphosate (GLY), deltamethrin (DEL), and chlorothalonil (CHL). Cell viability, membrane integrity, inflammation induction, and antioxidant activity were evaluated to determine differences in cellular response to the tested plant protection agents. In experimental models, all tested substances caused increased mortality of cells after only 24 h. Cell membrane damage was recorded under DEL and CHL influences. The largest disintegration of the cell membrane was due to the action of 100 μg/mL DEL for U-937 and CHL at 1 μg/mL for HL-60. GLY at a concentration of 3,600 μg/mL caused significant peroxidation of U-937 cells' lipids. CHL-induced inflammation in both types of cells tested. DEL and GLY also induced antioxidant activity in cells. These results lead to the conclusion that the tested pesticides act cytotoxically to the cells of the human immune system in doses to which both farmers and consumers are exposed.

Inga edulis is a fruit tree native from Central and South America. Different species of Inga have demonstrated high polyphenolic content and high antioxidant capacity. The oxidative stress significantly contributes to the development of several chronicle diseases, particularly age-related diseases. Therefore, photochemoprevention is an emerging interest in the use of naturally occurring antioxidants for their therapeutic use. A partial purification of the extract was carried out onto macroporous resin and the main components of I. edulis leaf extract and fraction were identified using UPLC-DAD-MS/MS as epicatechin, apigenin C-di-hexoside, myricetin- O -hexose-deoxyhexose, myricetin- O -deoxyhexose and vicenin-2, which was identified for the first time in I. edulis . Both extract and fraction presented high antioxidant capacity, the fraction exhibiting higher polyphenol and flavonoid contents and higher content of vicenin-2, suggesting that the fractioning process effectively resulted in the partial purification of the extract. The cytotoxicity and photostability were assessed in L929 fibroblast cells to evaluate whether I. edulis extract and fraction were suitable for topical application. The UVA and UVB irradiated extract and fraction did not decrease the antioxidant capacity and cell viability of L929 fibroblasts, demonstrating the photostability of the samples. The fractioning process successfully purified and enriched I. edulis extract, and both the extract and fraction are potential candidates to be safely incorporated in topical photochemopreventive formulations.

Context: Ephedrae Herba (EH), the dried stems and leaves of Ephedra sinica Stapf., E. intermedia Schrenk et C. A. Mey., or E. equisetina Bge. (Ephedraceae [Ephedra]) is used to treat respiratory diseases. Recently, especially in the Republic of Korea, EH has also been used for weight reduction. Objective: We evaluated the effects and molecular targets of methanol EH extract (EHM) on high-fat diet (HFD)-induced hyperlipidemic ICR mice. Materials and methods: EHM was orally administered (100 mg/kg body weight/day) for 3 weeks. We observed changes in body weight (BW), total cholesterol (TC), high-density lipoprotein-cholesterol, and triglycerides to evaluate the physiological changes induced by HFD or EHM administration. To evaluate lipid peroxidation and liver toxicity, malondialdehyde and blood alanine aminotransferase levels were measured. In addition to analyzing liver gene expression profiles, EHM target proteins were identified using a protein interaction database. Results: EHM administration for 3 weeks significantly ( p  < 0.05) decreased TC and triglyceride levels without altering BW in mice, and gene expression levels in the livers of EHM-treated mice were restored at 34.0% and 48.4% of those up- or down-regulated by hyperlipidaemia, respectively. Proteins related to DNA repair and energy metabolism were identified via protein interaction network analysis as molecular targets of EHM that play key roles in ameliorating hyperlipidaemia. Discussion and conclusions: EHM regulated hyperlipidaemia by decreasing total blood lipid and triglyceride levels in hyperlipidaemic mice. EHM showed preventive effects against hyperlipidaemia in mice, possibly via the regulation of DNA repair and the expression of energy metabolism-related genes and proteins.

Objective: Investigate Vitamin D 3 (VD 3 ) effect on the Acetylcholinesterase (AChE), oxidative damage and behavioral tests in animals subjected to Intracerebroventicular injection of Streptozotocin (ICV-STZ) simulating a Sporadic Dementia of Alzheimer's Type (SDAT) and treated with VD 3 (21 days)., Methods: Animals were divided into eight groups: Vehicle, VD12.5 μg/kg, VD42 μg/kg, VD125 μg/kg, STZ, STZ+VD12.5 μg/kg, STZ+VD42 μg/kg, STZ+VD125 μg/kg., Results: VD 3 prevented the increase in AChE in groups of VD42 µg/kg and VD125 µg/kg; in AChE of synaptossomes and TBARS levels prevented the increase in group VD125 µg/kg; in ROS levels there was not a significant difference; for the Carbonyl Content all doses prevented the increase. Total Thiols prevent the decrease in VD42 µg/kg and VD125 µg/kg, and Reduced Glutathione prevented the decrease in VD125 µg/kg, Oxidized Glutathione prevented the increase in VD125 µg/kg. In relation to behavioral tests, the VD 3 prevented the increase in time to find (days 2 and 3), in the time to find the platform (day 3) and in time spent in the quadrant (day 2). However, in relation to crossings there was not difference in groups. These results indicated the therapeutic effect of the VD 3 in model of STZ in rats.

This study was designed to describe the oral acute and subacute toxicities and underlying toxicological mechanisms of biogenic Zn NPs in mice. The Zn NPs were prepared by a green microwave-assisted synthesis method in the presence of Lavandula vera leaf extract. Determination of median lethal dose (LD 50 ) of Zn NPs and the subacute toxicity after 14 days of exposure was performed as a measurement of substance toxicity through general toxicological, hematological, serum, and histopathological investigations. The western blotting was used to determine the cleaved-caspase-3 expression in the sampled tissues. Flame atomic absorption spectrophotometer (AAS) was applied to estimate the Zn levels in tissues. The SEM analyses revealed that the biogenic Zn NPs were spherical-shaped with the size range of 30-80 nm. The LD 50 value above 5 g/kg indicated that biogenic Zn NPs could be classified as non-toxic chemicals. In subacute toxicity, no significant differences were found in the body weight as well as hematological and oxidative stress (OS) biomarkers after exposure to Zn NPs at the dose of 1 g/kg in comparison to the control. The AAS results indicated that Zn NPs were mainly distributed in the testis, liver, and brain. The findings of histology images of Zn NPs at the dose of 1 g/kg were similar to those of the control. Furthermore, no significant differences were observed in cleaved-caspase-3 expression after exposure to Zn NPs at the dose of 5 g/kg. The results demonstrated that changes in the OS were not related to caspase pathway and the no-observed-adverse-effect level (NOAEL) dose of biogenic Zn NPs in 14-days subacute toxicity study was lower than 1 g/kg.

Context: Mentha longifolia L. (Lamiaceae), a traditional medicinal herb, has been highly valued for exhibiting antimicrobial, antioxidant and antispasmodic properties., Objective: For the first time, the synergetic anti-inflammatory effects of deuterium depleted water (DDW) and M. longifolia essential oils (ML) were investigated in experimental sepsis., Materials and Methods: Fifty Wistar rats were divided into 5 groups (n = 10): negative control (laparotomy), CLP, treatment groups including the combination of DDWs (15 and 30 ppm) and ML (100 mg/kg b.w) and indomethacin. At 24 h after CLP induction, lipid peroxidation (LP), glutathione (GSH), glutathione in S-transferases (GST), ferric reducing ability of plasma (FRAP), myeloperoxidase (MPO), prostaglandin E2 (PGE2), and COX-2 expression were determined in the plasma and liver tissues., Results: Compared with the CLP group, the administration of DDWs and ML significantly (p < 0.05) prevented the increase of LP, COX-2 and PGE2 levels and liver enzymes. Additionally, the decreased levels of FRAP and GSH induced by sepsis were remarkably (p < 0.05) risen by the administration of DDWs and ML in comparison to the CLP group. However, no significant (p > 0.05) differences were observed regarding GST, ALP and bilirubin levels. Our results also proved the synergistic anti-inflammatory activities of the DDWs and ML. The anti-inflammatory effects of the DDWs and ML were confirmed by histopathological studies., Discussion and Conclusions: The combination of DDWs and ML exerted synergistic anti-inflammatory activity against CLP-induced sepsis possibly through modulating oxidative stress/antioxidant parameters.

Nimbolide, a triterpenoid isolated from flower of neem tree possess various therapeutic properties. The objective of the study was to assess the anti-arthritic activity of nimbolide in arthritis induced rats. Nimbolide (20 mg/kg per day) was given orally to arthritic rats induced with Complete Freund's Adjuvant and changes in paw volume, body weight, organ indices (thymus and spleen), arthritic score, biochemical parameters and proinflammatory cytokines levels were determined. Histopathological analysis was also performed. Western blot analysis was also performed. Rats treated with nimbolide displayed marked reduction in arthritic score, organ indices, volume of paw, edema formation, along with substantial enhancement in body weight. Histopathological findings showed significant reduction in destruction of joints and inflammation following nimbolide treatment. The protective action of arthritic rats treated with nimbolide was also substantiated by molecular and biochemical studies. The results of the study show that nimbolide treatment has markedly enhanced health and reduced inflammation via lessening the proinflammatory cytokines expression in arthritic rats. Hence, nimbolide may be used as a potent therapeutic drug in treating rheumatoid arthritis.

Objective: The present study aims to investigate the neuroprotective effect of caffeine against aluminum chloride (AlCl 3 )-induced neurotoxicity in rats. Methods: Twenty-one male albino rats were divided into 3 groups: control, AlCl 3 -intoxicated group that received daily oral administration of AlCl 3 (100 mg/kg for 30 days) and protected group injected daily with caffeine (20 mg/kg intraperitoneally) one hour before oral administration of AlCl 3 for 30 days. Levels of lipid peroxidation, reduced glutathione, and nitric oxide and the activities of acetylcholinesterase (AchE) and Na + /K + -ATPase were measured spectrophotometrically. Tumor necrosis factor-α (TNF-α) was evaluated by ELISA kit. Results: The data revealed evidence of oxidative and nitrosative stress in the cerebral cortex, hippocampus, and striatum of AlCl 3 -intoxicated rats. This was indicated from the increased levels of lipid peroxidation and nitric oxide together with the decreased level of reduced glutathione. Moreover, the daily AlCl 3 administration increased AchE and Na + /K + -ATPase activities and the level of TNF-α in the selected brain regions. Protection with caffeine ameliorated the oxidative stress induced by AlCl 3 in the cerebral cortex, hippocampus, and striatum. In addition, caffeine restored the elevated level of TNF-α in the hippocampus and striatum. This was accompanied by an improvement in the activities of AchE and Na + /K + -ATPase in the studied brain regions. Discussion and conclusions: The present findings clearly indicate that caffeine provides a significant neuroprotection against AlCl 3 -induced neurotoxicity mediated by its antioxidant, anti-inflammatory, and anticholinesterase properties.

We investigated how resveratrol affects lipid oxidation during experimental renal ischemia-reperfusion injury in rats. We used 48 adult male rats assigned to five groups: group 1, control; group 2, renal ischemia; group 3, renal ischemia + reperfusion; group 4, resveratrol + renal ischemia; group 5, resveratrol + renal ischemia + reperfusion. Plasma and renal tissue malondialdehyde (MDA), and erythrocyte and renal tissue glutathione (GSH) levels were measured and histologic changes in the renal tissue were examined. Ischemia-reperfusion affected the MDA-GSH balance adversely and caused histopathological changes in the renal tissue of the ischemia and ischemia + reperfusion groups. Resveratrol treatment normalized MDA and GSH levels as well as the histopathology that occurred in the renal tissue of the ischemia and ischemia + reperfusion groups.

The aim of this study was to investigate the effects of simultaneous supplementation of laying hens with dietary sources of n-3 polyunsaturated fatty acids (PUFA) and carotenoids on egg quality, fatty acids and carotenoid profile of the egg yolk and on feed and yolk lipid peroxidation. A 6-week experiment was carried out with 53-week old laying hens (96 Tetra SL) assigned to a control and three treatment groups supplemented with 5% flaxseeds and different levels of dried tomato waste (DTW, 2.5%, 5.0% and 10.0%). Hens from the groups supplemented with 5% and 7.5% DTW had a significantly lower average daily feed intake and laying percentage as compared to the control. Increased doses of dietary DTW enhanced yolk Roche colour score in direct correlation with the enrichment of egg yolk in carotenoids but decreased their transfer efficiency from feed to egg. After 4 weeks, egg yolk from hens fed with 5% flaxseeds and 7.5% DTW had increased lutein and zeaxanthin levels (by 29% and 24%, respectively) and the colour score was 3.5 fold higher compared to the control group. As a result of the dietary supplementation with flaxseed, the n-3 fatty acid content was 3.1-3.7-fold higher in egg yolk compared with the control and the n-6/n-3 ratio decreased from 18.3 (control) to 4.1-5.4 in supplemented diets. Dietary supplementation with 5% DTW effectively prevented lipid oxidation of eggs enriched with n-3 PUFA, but the increase in DTW content depressed the absorption and deposition of n-3 PUFA in egg yolk.

Objective: JM-20, a novel hybrid synthetic molecule, has been reported to have antioxidant, mitoprotective, anti-excitotoxic, anti-apoptotic and anti-inflammatory properties. However, the neuroprotective effect of JM-20 against memory impairment in preclinical AD-like models has not been analyzed. The aim of this study was to evaluate the potential neuroprotection of JM-20 that preserves essential memory process from cholinergic dysfunction and other molecular damages., Methods: The effects of JM-20 on scopolamine (1 mg/kg)-induced cognitive disorders were studied. Male Wistar rats (220-230 g) were treated with JM-20 and/or scopolamine, and behavioral tasks were performed. The AChE activity, superoxide dismutase activity, catalase activity, MDA and T-SH level on brain tissue were determined by spectrophotometric methods. Mitochondrial functionality parameters were measured after behavioral tests. Histological analyses on hippocampus and prefrontal cortex were processed with hematoxylin and eosin, and neuronal and axonal damage were determined., Results: The behavioral, biochemical and histopathological studies revealed that oral pre-treatment with JM-20 (8 mg/kg) significantly attenuated the scopolamine-induced memory deficits, mitochondrial malfunction, oxidative stress, and prevented AChE hyperactivity probably due to specific inhibition of AChE enzyme. It was also observed marked histological protection on hippocampal and prefrontal-cortex regions., Conclusions: The multimodal action of this molecule could mediate the memory protection here observed and suggest that it may modulate different pathological aspects of memory deficits associated with AD in humans.

Objectives: In view of the increasing risk of lead on human health, the present study has been carried out to investigate the neuroprotective effect of omega-3 fatty acid on chronic lead-induced neurotoxicity and behavioral impairment in rats. Methods: Different neurobehavioral parameters, biochemical assays, and histopathological analyses in brain regions of rats were conducted. Results: Rats exposed to different doses of lead (lead acetate 2.5, 5.0, 7.5 mg/kg body weight p.o. for 90 days) caused a significant decrease in body weight, brain weight, and behavioral changes as compared to controls. Abnormal histopathological and increased levels of lead in blood and brain regions increased the levels of ROS, LPO, PCC and decreased the levels of GSH with concomitant reduction in SOD, CAT, and GPx activities in the brain region of rats treated with different doses of lead as compared to controls. Co-treatment of lead with omega-3 fatty acid (500 mg/kg body weight p.o. for 90 days) decreased the levels of ROS, LPO, PCC, and increased the level of GSH, also increased SOD, CAT, and GPx activity and showed improvements in behavioral as well as histopathological changes as compared to lead-treated groups. Discussion: Our results proved that omega-3 fatty acid improved behavioral deficits, altered histopathological and oxidative stress in lead-intoxicated rats. Among three different doses, 2.5 mg/kg b.wt. of lead along with omega-3 fatty acid was the most preventive dose for the neurotoxicity. This work reveals the potential of omega-fatty acid as a protective drug for lead neurotoxicity.

Imidacloprid (IMI), a neonicotinoid insecticide, is widely used to control pests in agriculture. We investigated the changes in antioxidant enzyme activities, lipid peroxidation levels, biochemical effects, genotoxic effect, and immunotoxic effect of sublethal doses (0.25, 0.50, 0.75, and 1.00 µg) of IMI at different time periods (24, 48, 72, and 96 h) on a model organism, Galleria mellonella L. The results indicated that there were dose-dependent increases in both antioxidant enzyme activities (SOD and CAT) and MDA levels. Protein content was not affected by IMI at 24th and 48th, whereas it was decreased by the highest dose of IMI (1.00 µg) at 72nd and 96th h. Lipid and carbohydrate contents were reduced with increasing doses of IMI. Micronucleus frequency significantly increased in all IMI doses. All IMI doses caused a significant decrease in THC at 24th, 48th, and 72nd h. Our results can help to illustrate the effects of IMI in target organisms and indirectly may aid to discover potential risk of it on nontarget organisms. Future studies, at molecular levels, will be helpful in understanding the mechanism of action of IMI on these biomarkers.

This study aimed to detect the most deleterious ROS for goat sperm and then supplemented the extender with a proper antioxidant. For this, 12 adult goats (aged 1-7) were used. Fresh samples were submitted to challenge with different ROS (superoxide anion, hydrogen peroxide, and hydroxyl radical) and malondialdehyde (MDA-toxic product of lipid peroxidation). After experiment 1, sperms were cryopreserved in extenders supplemented to glutathione peroxidase (Control: 0 UI/mL; GPx1: 1 UI/mL; GPx5: 5 UI/mL, and GPx10: 10 UI/mL) and catalase (Control: 0 UI/mL; CAT60: 60 UI/mL; CAT120: 120 UI/mL, and CAT240: 240 UI/mL). Each sample was evaluated by motility, plasma membrane integrity (eosin/nigrosin), acrosome integrity (fast green/rose bengal), sperm morphology, assay of the sperm chromatin structure, mitochondrial activity (3,3-diaminobenzidine), and measurement of lipid peroxidation (thiobarbituric acid reactive substances [TBARS]). It was possible to observe a mitochondrial dysfunction (DAB-Class IV) and low membrane integrity after hydrogen peroxide action. However, the high rates of TBARS were observed on hydroxyl radical. CAT240 presents the lower percentage of plasma membrane integrity. It was possible to attest that hydrogen peroxide and hydroxyl radical are the more harmful for goat sperm. Antioxidant therapy must be improving perhaps using combination between antioxidants.

Objectives: To evaluate how safflower oil (SFO) influences brain electrophysiology and cortical oxidative status in the offspring, mothers received a diet with SFO during brain development period., Methods: Beginning on the 14th day of gestation and throughout lactation, rats received safflower (safflower group - SG) or soybean oil (control group - CG) in their diet. At 65 days old, cortical spreading depression (CSD) and cortex oxidative status were analyzed in the offspring., Results: SG presented reduction of the CSD velocity as compared to the CG (SG: 3.24 ± 0.09; CG: 3.37 ± 0.07 mm/min). SFO reduced levels of lipid peroxidation by 39.4%. SG showed the following increases: glutathione-S-transferase, 40.8% and reduced glutathione, 34.3%. However, SFO decreased superoxide dismutase by 40.4% and catalase by 64.1%. To control for interhemispheric effects, since CSD was recorded only in the right cortex, we evaluated the oxidative status in both sides of the cortex; no differences were observed., Discussion: Data show that when SFO is consumed by the female rats during pregnancy and lactation, the offspring present long-term effects on brain electrophysiology and cortical oxidative state. The present study highlights the relevance of understanding the SFO intake of pregnant and lactating mammals.

Objective: We aimed to investigate the effect of Sicyos angulatus (SA) ethanolic extracts as antioxidants and potential treatments for liver disease., Methods: To establish a mouse model of liver injury, C57BL/6 male mice were injected via the caudal vein with a single dose of concanavalin A (Con A, 15 mg kg -1 ). SA extracts were administered once by oral gavage 30 min before Con A injection., Results: In vitro studies showed that SA decreased tert-butyl hydroperoxide (t-BHP)-induced reactive oxygen species (ROS) production. SA administration reduced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as hepatic ROS levels, in a dose-dependent manner. Moreover, SA increased the activities of the hepatic antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner. Furthermore, SA treatment reduced pro-apoptotic protein levels. Con A-mediated cytosolic release of Smac/DIABLO and apoptosis-inducing factor (AIF), which are markers of necrosis, were dramatically decreased in HepG2 cells treated with SA., Conclusion: SA ameliorated liver injury and might be a good strategy for the treatment of liver injury.

Context: Schisandrae chinensis fructus, the dried ripe fruit of Schisandra chinensis (Turcz.) Baill. (Magnoliaceae) has been used for thousands of years as a traditional Chinese herb, which can attenuate and prevent the development of cardiovascular events., Objective: To evaluate the effects of the ethanol extracts from Schisandrae chinensis fructus fruit (EESC) on experimental atherosclerosis (AS) in rats., Materials and Methods: Treatment with EESC (0.35, 0.7, 1.4 g/kg/d, i.g.) and simvastatin (4 mg/kg/d, i.g.) on AS rats for 3 weeks. Sprague-Dawley rats on normal chow and under water treatment were used as control. The content of schisandrin, schisandrin A and schisandrin B in EESC was detected by HPLC. Aortic pathology changes, serum biochemical indices and nuclear factor E2-related factor 2 (Nrf-2) and heame oxygenase-1 (HO-1) expressions were measured., Results: Schisandrin, schisandrin A and schisandrin B contents were 291.8, 81.46 and 279.1 mg/g of dry weight, respectively. EESC significantly reduced the aortic plaque area (76.5, 90.5 and 73.9% reduction), regulated the levels of serum lipid (p < 0.05), enhanced the antioxidant enzyme activities (p < 0.01), reduced the malondialdehyde levels (72.5, 69.3, 67.3%), and up-regulated the Nrf-2 and HO-1 expression (p < 0.05). Furthermore, EESC reduced the levels of oxidized-LDL and endothelin-1 and thromboxane B2 but increased that of 6-keto prostaglandin F1α (p < 0.05). Acute toxicity was calculated on mice to be LD 50  > 20 g/kg., Conclusions: EESC positively affects the treatment of AS in vivo and the findings will provide a reliable theoretical basis for developing novel therapeutics.

Primaquine (PQ) ureidoamides 5a-f were screened for antimicrobial, biofilm eradication and antioxidative activities. Susceptibility of the tested microbial species towards tested compounds showed species- and compound-dependent activity. N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]-4-methylpentanamide (5a) and 2-(4-chlorophenyl)-N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]acetamide (5d) showed antibacterial activity against S. aureus strains (MIC = 6.5 µg/ml). Further, compounds 5c and 5d had weak antibacterial activity against Escherichia coli and Pseudomonas aeruginosa. None of the tested compounds showed a wide spectrum of antifungal activity. In contrast, most of the compounds exerted strong activity in a biofilm eradication assay against E. coli, P. aeruginosa and Candida albicans, comparable to or even higher than gentamycin, amphotericin B or parent PQ. The most active compounds were 5a and 5b. Tested compounds were inactive against biofilm formation by C. parapsylosis, Enterococcus faecalis, C. tropicalis and C. krusei. Compounds 5b-f significantly inhibited lipid peroxidation (80-99%), whereas compound 5c presented interesting LOX inhibition.

The neurotrophin family of proteins and their receptors act as important proliferative and pro-survival factors in differentiation of nerve cells and are thought to play key roles in the development of reproductive tissues and normal function of spermatozoa. The objective of the present study was to evaluate the effect of Brain-Derived Neurotrophic Factor (BDNF) on the sperm viability and motility, lipid peroxidation (LPO), mitochondrial activity and concentration of leptin, nitric oxide (NO) and insulin in normozoospermic men. Semen samples from 20 normozoospermic men were divided into three groups: (i) control, (ii) BDNF and (iii) BDNF + K252a. BDNF and K252a were added in the dose of 0.133 and 0.1 nM, respectively. Viability was assessed by eosin-nigrosin staining technique, and motility was observed by microscopy. NO concentration and mitochondrial activity were measured with flow cytometry, and LPO was analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Results showed that exogenous BDNF at 0.133 nM could significantly (p < 0.05) influence viability, motility, NO concentration, mitochondrial activity and LPO content. Secretions of insulin and leptin by human sperm were increased in cells exposed to the exogenous BDNF, whereas viability, mitochondrial activity and insulin and leptin secretions were decreased in cells exposed to the K252.

Objectives: Loranthus micranthus is widely used in Nigerian folklore treatment of male infertility and diabetes complications. We investigated this claim in rats rendered diabetic by streptozotocin (STZ)., Methods: Induction of diabetes mellitus in adult male Wistar rats was by intraperitoneal injection of STZ (60  mg/kg). The diabetic rats were thereafter treated orally once/day with 5 mg/kg Gilbenclamide or L. micranthus (100 mg/kg or 200 mg/kg) and monitored for 14 days. Clinical observations, hormonal profile, oxidative stress parameters, glucose metabolism enzymes, histopathological examination, apoptotic marker immunoreactivity and western blotting in testes and sperm parameters were evaluated to examine effects of L. micranthus on STZ-diabetic rats., Results: L. micranthus treatment significantly reduced the blood glucose level (45.9% and 84.7% on the 7th and 14th post-treatment days, respectively); increased antioxidant status, improved microarchitecture of testes, reduced lipid peroxidation and increased BCl-2 protein expression in diabetic rats relative to control. Furthermore, treatment with L. micranthus increased steroidogenic enzymes activities, levels of steroid hormones and improved sperm quality, relative to control., Conclusion: The anti-diabetic and aphrodisiac properties exhibited by L. micranthus could be contingent on its ability to restore a balance to the compromised redox status that characterizes male reproductive dysfunction in diabetes.

Objectives: The present study was designed to evaluate the effect of hesperetin on haloperidol-induced orofacial dyskinesia and catalepsy in Wistar male albino rats., Methods: Haloperidol (1 mg/kg, ip) was administered for 21 successive days to induce orofacial dyskinesia and catalepsy. Hesperetin (50 and 100 mg/kg, po) was administered 10 min prior to the injection of haloperidol for 21 successive days. Vacuous chewing movements (VCMs), tongue protrusions, catalepsy, and locomotor activity scores were recorded on 7th, 14th, and 22nd day of drug treatment. After behavioral testing, animals were sacrificed and various biochemical parameters such as brain levels of dopamine, serotonin, malondialdehyde, and reduced glutathione (GSH); and superoxide dismutase (SOD) and catalase activities were estimated., Results: Chronic administration of haloperidol significantly increased VCMs, tongue protrusions, and catalepsy in rats. It also produced hypolocomotion in rats. Hesperetin significantly inhibited haloperidol-induced VCMs, tongue protrusions, and catalepsy. Haloperidol significantly increased brain levels of malondialdehyde, decreased brain GSH, SOD, and catalase activities; and also decreased brain dopamine and serotonin levels. Hesperetin significantly reversed haloperidol-induced increase in brain oxidative stress and decrease in brain dopamine and serotonin levels., Discussion: Hesperetin significantly ameliorated haloperidol-induced orofacial dyskinesia and catalepsy possibly through alleviation of oxidative stress and increase in brain dopamine and serotonin levels. Thus, hesperetin may be explored further as a possible therapeutic agent for clinical management of neuroleptic drug-induced tardive dyskinesia.

Objectives Diabetic neuropathy (DN) induces lifetime disability and there is currently no effective therapy to treat or to minimize patients suffering, so it is thereby imperative to develop therapeutic strategies for this disease. Since oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation are crucial mechanisms in development and progression of DN, it is important to explore tools by which one can reduce factors related to these pathways. Herein, the understandings of the sildenafil neuroprotective effect through increase of cGMP level and the mediation of oxidative stress, apoptosis, and inflammation pathways on neurotoxicity induced by high glucose (HG) in PC12 cells as an in vitro cellular model for DN were investigated. Methods We reported that the PC12 cells pre-treatment with sildenafil (0.008 μM) for 60 min and then exposing the cells to HG (25 mM for 72 h) or normal glucose (NG) (5 mM for 72 h) condition, show: Results (1) significant attenuation in reactive oxygen species, MDA and TNF-a levels, Bax/Bcl-2 ratio, expression of caspase 3 and UCP2 proteins; (2) significant increase in viability, GSH/GSSG ratio, mitochondrial membrane potential, and ATP levels. Conclusion All these data together led us to propose neuroprotective effect of sildenafil is probably through its antioxidant, antiapoptotic, and anti-inflammatory activities. Of course, further studies are required to explain the underlying mechanism of the sildenafil effects.

The objective of present study was in vitro and in vivo evaluation of hepatoprotective and antioxidant activity of Quercetin nanoparticles (Q NPs) against toxicity induced by aflatoxin B1. The Q NPs were prepared using precipitation method. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. The NPs were characterized in terms of size and morphology using dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The level of parameters, such as cell death, ROS formation, lipid peroxidation, mitochondrial membrane potential and cellular glutathione (GSH) content, in the aflatoxin B1-treated and non-treated hepatocytes were determined and the mentioned markers were assessed in the presence of Q NPs. The prepared NPs showed particle size of 52.70 nm with polydispersity index (PDI) of 0.18. In contrast to free Q, the administration of Q NPs more efficiently decreased the rate of ROS formation, lipid peroxidation and improved cell viability, mitochondrial membrane potential and glutathione level and showed a significant hepatoprotective efiect by reducing levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. It is suggested that the Q NPs is a promising candidate for drug delivery, which enhances the hepatoprotective effect of Q against the cytotoxic effects of aflatoxin B1.

Argan oil (AO) is rich in oleic and linoleic acids, polyphenols, sterols, and tocopherols. This composition gives it numerous beneficial pharmacological effects such as hypolipemiant, hypotensive, and antiproliferative. Oxidative stress is a mechanism of cell death induced by seizures and status epilepticus (SE). This study aims at investigating AO effects on (i) latency to first seizure, seizure severity, weight loss, mortality rate, (ii) lipid peroxidation level, nitrite level, and catalase activity in the hippocampus after SE induced by pilocarpine (PC). Wistar rats (1-month old) were daily administered by oral gavage with AO (1 ml/100 g/day) or with NaCl 0.9% during 2 months before receiving PC (400 mg/kg). After the PC injection, all groups were observed for 24 h. The catalase activity, the lipid peroxidation, and nitrite concentrations were measured using spectrophotometric methods. AO pretreatment increased the latency to first seizures, decreased the weight loss, and reduced mortality rate after SE. AO pretreatment produces significant decrease of the lipid peroxidation and nitrite levels. On the contrary, AO increased the catalase activity in rat hippocampus after seizures. For the first time, our results suggest that AO pretreatment is capable of attenuating seizure severity and oxidative stress in the hippocampus of Wistar rats. This indicates that AO may exhibit a neuroprotection against the temporal lobe epilepsy. Further investigations are in progress to confirm this pharmacological property.

Cystitis is defined as an inflammation of the bladder caused by a bacterial infection, and it can be dangerous and painful when it spreads through the internal organs. In this study, antioxidant effects of hydroxylfasudil (HF) at the enzymatic and molecular level on kidney and liver tissues in cystitis rat model, which is caused by inflammation of the rat bladder with a protamine sulphate (PS), was examined. Quantitative changes of reduced glutathione (GSH) and lipid peroxidation (LPO) levels, which are a marker for oxidative stress, were determined in rat kidney and liver tissues for each groups. And then molecular and biochemical impact of HF treatment on antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) in cystitis model were studied. The results suggest that HF could be beneficial to the renal and hepatic antioxidant system. Thus, HF might be used as a novel therapeutics agent to eliminate interstitial cystitis.

Ferroptosis is a recently recognized form of regulated cell death that is characterized by lipid peroxidation. However, the molecular mechanisms regulating ferroptosis are largely unknown. In this study, we report that the RNA-binding protein ELAVL1/HuR plays a crucial role in regulating ferroptosis in liver fibrosis. Upon exposure to ferroptosis-inducing compounds, ELAVL1 protein expression was remarkably increased through the inhibition of the ubiquitin-proteasome pathway. ELAVL1 siRNA led to ferroptosis resistance, whereas ELAVL1 plasmid contributed to classical ferroptotic events. Interestingly, upregulated ELAVL1 expression also appeared to increase autophagosome generation and macroautophagic/autophagic flux, which was the underlying mechanism for ELAVL1-enhanced ferroptosis. Autophagy depletion completely impaired ELAVL1-mediated ferroptotic events, whereas autophagy induction showed a synergistic effect with ELAVL1. Importantly, ELAVL1 promoted autophagy activation via binding to the AU-rich elements within the F3 of the 3'-untranslated region of BECN1/Beclin1 mRNA. The internal deletion of the F3 region abrogated the ELAVL1-mediated BECN1 mRNA stability, and, in turn, prevented ELAVL1-enhanced ferroptosis. In mice, treatment with sorafenib alleviated murine liver fibrosis by inducing hepatic stellate cell (HSC) ferroptosis. HSC-specific knockdown of ELAVL1 impaired sorafenib-induced HSC ferroptosis in murine liver fibrosis. Noteworthy, we retrospectively analyzed the effect of sorafenib on HSC ferroptosis in advanced fibrotic patients with hepatocellular carcinoma receiving sorafenib monotherapy. Attractively, ELAVL1 upregulation, ferritinophagy activation, and ferroptosis induction occurred in primary human HSCs from the collected human liver tissue. Overall, these results reveal novel molecular mechanisms and signaling pathways of ferroptosis, and also identify ELAVL1-autophagy-dependent ferroptosis as a potential target for the treatment of liver fibrosis. Abbreviations: ACTA2/alpha-SMA: actin, alpha 2, smooth muscle, aorta; ACTB/beta-actin: actin beta; ARE: AU-rich element; ATG: autophagy related; BDL: bile duct ligation; BECN1: beclin 1; BSO: buthionine sulfoximine; COL1A1: collagen type I alpha 1 chain; ELAVL1/HuR: ELAV like RNA binding protein 1; FDA: fluorescein diacetate; FTH1: ferritin heavy chain 1; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic-pyruvic transaminase; GPX4: glutathione peroxidase 4; GSH: glutathione; HCC: hepatocellular carcinoma; HSC: hepatic stellate cell; LCM: laser capture microdissection; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MDA: malondialdehydep; NCOA4: nuclear receptor coactivator 4; PTGS2: prostaglandin-endoperoxide synthase 2; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TBIL: total bilirubin; TEM: transmission electron microscopy; TGFB1: trasforming growth factor beta 1; UTR: untranslated region; VA-Lip-ELAVL1-siRNA: vitamin A-coupled liposomes carrying ELAVL1-siRNA.

Purpose: The current study was undertaken to evaluate radioprotective effects of selenium (Se) nanoparticles in irradiation-induced nephropathy of mice model compared to sodium selenite., Materials and Methods: Forty-five mice were divided into three major groups including control, Se nanoparticle, and sodium selenite. Each major group was further subdivided into three more groups receiving various doses of 0, 2, and 8 Gy gamma irradiation. Both of the supplements were administered intraperitoneally with the dose of 0.1 mg/kg for 14 consecutive days. At the end of each week, the animals were exposed to gamma radiation and 48 h after the last exposure, the animals were humanely euthanized, then blood and renal tissue samples were taken. Serum creatinine, urea, cystatin C, and beta-2-microglobulin levels as well as activities of renal antioxidant enzymes, superoxide dismutase, glutathione peroxidase and catalase, also malondialdehyde level, total antioxidant capacity, renal tissue Se content, and histopathological features were assessed., Results: The results showed that both of the supplements could normalize aforementioned indices. However, selenium nanoparticles (Se-NPs) were more effective than sodium selenite., Conclusions: Conclusively, Se-NPs as an emerging potent antioxidant agent can protect against irradiation-induced nephropathy.

The present study reports a simple and eco-friendly synthesis of silver nanoparticles (AgNPs) using leaf extract of Rhynchosia suaveolens. UV-Vis analysis of R. suaveolens synthesized AgNPs (RS-AgNPs) showed surface plasmon resonance (SPR) peak at 426 nm. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis revealed that RS-AgNPs were 10-30 nm in size with spherical shape. X-ray diffraction (XRD) analysis of RS-AgNPs confirmed the crystalline nature with face-centered cubic (FCC) lattice. Fourier transform infrared (FTIR) interprets that polyphenols and proteins take part in bioreduction and capping of RS-AgNPs. RS-AgNPs exhibited dose-dependent inhibition of proliferation of different cancer cells including DU145 and PC-3(human prostate carcinoma cell lines), SKOV3 (human ovarian carcinoma) and A549 (human lung adenocarcinoma)with IC 50 values of 4.35, 7.72, 4.2 and 24.7 μg/mL, respectively. The plausible reasons behind anticancer activity of RS-AgNPs were explained using different assays on the most susceptible SKOV3 cells. RS-AgNPs induced oxidative stress in SKOV3 cells by generating reactive oxygen species (ROS), enhancing lipid peroxidation (LPO) levels and decreasing glutathione (GSH) levels. RS-AgNPs induced the apoptosis of SKOV3 cells by up regulating the caspase-3, caspase -8, caspase -9, p53 and BAX and down regulating the antiapoptotic protein Bcl-2. Further, RS-AgNPs showed elevation of caspase 3/7 activity and also exhibited antimigratory effect by inhibiting the migration of SKOV3 cells into the wounded area. The findings suggested that biogenic RS-AgNPs provide an alternative approach to overcome several limitations of chemotherapy.

Aluminum (Al) toxicity is a major factor limiting plant productivity. The objective of the present study was to develop the mechanisms of boron (B) alleviating aluminum toxicity in citrus. The results showed that aluminum toxicity severely hampered root elongation. Interestingly, under aluminum exposure, boron supply improved superoxide dismutase activity while reducing peroxidase, catalase and polyphenol oxidase activities. Likewise, the contents of H 2 O 2 , lipid peroxidation, protein and proline in roots were markedly decreased by boron application under aluminum exposure. Our results demonstrated that boron could alleviate aluminum toxicity by regulating antioxidant enzyme activities in the roots.

We investigated possible healing effects of melatonin (MEL) on biochemical and histological changes in the lungs of rat offspring caused by exposure to nicotine (NT) in utero. Pregnant rats were divided randomly into five groups. The SP group was treated with physiological saline. The EA group was treated with ethyl alcohol. The MEL group was treated with MEL. The NT group was treated with NT. The NT + MEL group was treated with NT and MEL. At the end of the study, the biochemistry and histopathology of lung tissue of the offspring were examined. Reduced alveolar development and increased numbers of alveolar macrophages and mast cells were observed in the NT group compared to the SP, EA and MEL groups. We also found increased malondialdehyde (MDA) levels and decreased total glutathione (GSH) levels in the NT group. Application of MEL ameliorated the histological and biochemical damage caused by NT. The number of alveoli was greater in the NT + MEL group than in the NT group. Also, the increased numbers of alveolar macrophages and mast cells resulting from exposure to NT were decreased following MEL treatment. We found that MEL caused a significant decrease in the level of MDA. Maternal exposure to NT caused significant structural and biochemical changes in the lungs of the offspring and administration of MEL ameliorated the changes.

Context: There have been no reports of the extraction of essential oil (EO) from white cabbage [Brassica oleracea L. var. capitata (L.) Alef. f. alba DC. (Brassicaceae)] (Bocfal) or its chemical composition, antioxidant activity, or hepatoprotective effects., Objective: To extract Bocfal EO, to identify and quantify its chemical components, to assess their antioxidant capacity, and to evaluate the hepatoprotective properties of Bocfal EO., Materials and Methods: Bocfal EO was obtained using hydrodistillation (200 mm Hg/58 °C). The chemical composition was analyzed using GC-MS and was quantified using GC-FID. The antioxidant activity of Bocfal EO and its main constituents was evaluated using TBARS in rat brain homogenates. A Bocfal EO hepatoprotective effect (192 mg/kg) on acute carbon tetrachloride (CT)-induced liver damage was determined in rats using biochemical markers and histological analysis. Diallyl disulphide (DADS) (1 mmol/kg) was used as a control for comparison., Results: Bocfal EO contained organic polysulphides (OPSs), such as dimethyl trisulphide (DMTS) 65.43 ± 4.92% and dimethyl disulphide (DMDS) 19.29 ± 2.16% as major constituents. Bocfal EO and DMTS were found to be potent TBARS inhibitors with IC 50 values of 0.51 and 3 mg/L, respectively. Bocfal EO demonstrated better hepatoprotective properties than did DADS (p < 0.05), although both slightly affected the hepatic parenchyma per se, as observed using histopathology., Discussion and Conclusion: The antioxidant properties of Bocfal EO and DMTS may be the mechanism of hepatoprotective action; the parenchymal disturbances by Bocfal EO or DADS alone may be related to the high doses used.

Context: Visceral leishmaniasis is a protozoan disease caused by Leishmania donovani parasite. The genus Sterculia (Malvaceae) possesses ethnobotanical potential against this protozoan infection., Objective: Determining the potential role of methanol bark extracts from Sterculia villosa Roxb (SVE) and its phytoconstituents against Leishmania donovani promastigotes., Materials and Methods: SVE was analysed by TLC, UV-Vis, IR spectroscopy and biochemical assays. Antileishmanial potential of SVE (0.5-130 μg/mL for 72 h) was characterized by MTT assay. Fluorescent microscopy was performed to validate the IC 50 dose. To determine the effect of SVE on promastigotes, reactive oxygen species (ROS) and superoxide generation, lipid peroxidation and DNA fragmentation assays were performed. Molecular aggregation of compounds was determined by atomic force microscopy (AFM). Extent of cytotoxicity of SVE at IC 50 dose was determined against RAW 264.7 macrophages, peritoneal macrophages and murine RBCs. In vivo cytotoxicity of SVE was evaluated in BALB/c mice., Result: SVE exhibited reverse dose dependent antileishmanial activity when 130-0 μg/mL doses were tested against promastigotes. The IC 50 and IC 70 values were found to be 17.5 and 10 μg/mL, respectively. SVE at IC 50 dose demonstrated elevated level of ROS, superoxide, lipid peroxidation and DNA fragmentation against promastigotes with no cytotoxicity. AFM analysis suggested increasing size of molecular aggregation (31.3 nm < 35.2 nm < 2.93 μm) with increase in concentration (10 μg < 17.5 μg < 130 μg)., Discussion and Conclusions: The study elucidates the antileishmanial potential of SVE against Leishmania donovani promastigotes by exerting oxidative stress and DNA damage. In sum, SVE can be explored as an immunotherapeutic candidate against leishmaniasis and other infectious diseases.

Context: Aerva pseudotomentosa Blatt. & Hallb. (Amaranthaceae), commonly called "Bui";, is a medicinal plant of the arid region. It is used for the treatment of inflammatory disorders, such as rheumatic pain, and healing of wounds, which are associated with oxidative stress., Objective: The present study evaluated the antioxidant potential of Aerva pseudotomentosa leaves by in vitro models and its anti-inflammatory effect in rats., Material and Methods: The aqueous extract (APAE) was analyzed by HPTLC and HPLC. The antioxidant effect of APAE was evaluated by various in vitro methods [DPPH (1, 1-diphenyl-2-picryl-hydrazil) and hydrogen peroxide free radical scavenging, reducing power, and anti-lipid peroxidation assays]. Anti-inflammatory effect was studied in carrageenan and formalin-induced paw oedema models in rats. APAE (200 and 400 mg/kg) and standard drug, indomethacin (10 mg/kg), were administered orally 1 h before carrageenan/formalin administration and inflammation was noted up to 5 h., Results: HPLC analysis of APAE revealed the presence of rutin. APAE showed significant scavenging effect on DPPH (IC 50 49.37 μ g/mL) and peroxide (IC 50 288.2 μ g/mL) radicals. The extract exhibited reducing potential and inhibition of lipid peroxidation. APAE treatment significantly attenuated mean increase in paw volume and exhibited inhibition of paw oedema in both in vivo models with inhibition of 45.11% and 49.42%, respectively at 5 h., Discussion and Conclusion: APAE exhibited in vitro antioxidant and anti-inflammatory activities. Anti-inflammatory effect of APAE may be attributed to its antioxidant potential, due to the presence of rutin and other phenolics. This study substantiates folk use of leaves in inflammatory disorders.