Mechanistic insights into the metabolic pathways of vanillin: unraveling cytochrome P450 interaction mechanisms and implications for food safety.

Vanillin, a key flavor compound found in vanilla beans, is widely used in the food and pharmaceutical industries for its aromatic properties and potential therapeutic benefits. This study presents a comprehensive quantum chemical analysis to elucidate the interaction mechanisms of vanillin with CYP450 enzymes, with a focus on mechanism-based inactivation. Three potential inactivation pathways were evaluated: aldehyde deformylation, methoxy dealkylation, and acetal formation. Aldehyde deformylation was identified as the most energy-efficient, involving the removal of the aldehyde group from vanillin and leading to the formation of benzyne intermediates that could react with the iron porphyrin moiety of CYP450, potentially resulting in enzyme inactivation. Further investigation into the interactions of vanillin with CYP2E1 and CYP1A2 was conducted using molecular docking and molecular dynamics (MD) simulation. The docking analyses supported the findings from DFT studies, wherein vanillin revealed high binding affinities with the studied isozymes. Moreover, vanillin occupied the main binding site in both isozymes, as evidenced by the inclusion of the heme moiety in their binding mechanisms. Employing a 100 ns molecular dynamics simulation, we scrutinized the interaction dynamics between vanillin and the two isozymes of CYP450. The assessment of various MD parameters along with interaction energies revealed that vanillin exhibited stable trajectories and substantial energy stabilization during its interaction with both CYP450 isozymes. These insights can guide future research and ensure the safe application of vanillin, especially in scenarios where it may interact with CYP450 enzymes.

Advancements in technology and innovation for sustainable agriculture: Understanding and mitigating greenhouse gas emissions from agricultural soils.

In recent decades, Technology and Innovation (TI) have shown tremendous potential for improving agricultural productivity and environmental sustainability. However, the adoption and implementation of TI in the agricultural sector and its impact on the environment remain limited. To gain deeper insights into the significance of TI in enhancing agricultural productivity while maintaining environmental balance, this study investigates 21 agriculture-dependent Asian countries. Two machine learning techniques, LASSO (Least Absolute Shrinkage and Selection Operator) and Elastic-Net, are employed to analyze the data, which is categorized into three regional groups: ASEAN (Association of Southeast Asian Nations), SAARC (South Asian Association for Regional Cooperation), and GCC (Gulf Cooperation Council). The findings of this study highlight the heterogeneous nature of technology adoption and its environmental implications across the three country groups. ASEAN countries emerge as proactive adopters of relevant technologies, effectively enhancing agricultural production while simultaneously upholding environmental quality. Conversely, SAARC countries exhibit weaker technology adoption, leading to significant fluctuations in environmental quality, which in turn impact agricultural productivity. Notably, agricultural emissions of N2O (nitrous oxide) and CO2 (carbon dioxide) in SAARC countries show a positive association with agricultural production, while CH4 (methane) emissions have an adverse effect. In contrast, the study reveals a lack of evidence regarding technological adoption in agriculture among GCC countries. Surprisingly, higher agricultural productivity in these countries is correlated with increased N2O emissions. Moreover, the results indicate that deforestation and expansion of cropland contribute to increased agricultural production; however, this expansion is accompanied by higher emissions related to agricultural activities. This research represents a pioneering empirical analysis of the impact of TI and environmental emission gases on agricultural productivity in the three aforementioned country groups. It underscores the imperative of embracing relevant technologies to enhance agricultural output while concurrently ensuring environmental sustainability. The findings of this study provide valuable insights for policymakers and stakeholders in formulating strategies to promote sustainable agriculture and technological advancement in the context of diverse regional dynamics.

Formulation of Glibenclamide proniosomes for oral administration: Pharmaceutical and pharmacodynamics evaluation.

Glibenclamide (GB), oral antidiabetic sulfonylurea, is used in the management of diabetes mellitus type II. It suffers from low bioavailability due to low water solubility. This work aimed to enhance the dissolution of GB by formulating the drug as a proniosomes which then improves the pharmacological effect. GB proniosomal formulations were prepared using a slurry method with sucrose as a carrier. The formulations were characterized by particle size, zeta potential, entrapment efficiency %, flow properties of the powder, and in vitro dissolution study. The pharmacological effect was also assessed by determining and measuring the fasting blood glucose level (BGL) before and after the treatment. Formulating GB proniosomes with the slurry method produces a free-flowing powder with a particle size range from 190.050 ± 43.204 to 1369.333 ± 150.407 nm and the zeta potential was above 20 mV (-24 to -58 mV), indicating good stability. The dissolution rate for all formulations was higher than that of the pure drug, indicating the efficiency of the proniosome in enhancing the drug solubility. A significant reduction in the fasting blood glucose level (73 %) was observed in animals treated with proniosomal formulation with no sign of liver damage. In contrast, the pharmacodynamics results show a significant reduction in fasting blood glucose level for animals treated with proniosomes compared to a 17.6 % reduction in BGL after treatment with pure drug. Moreover, the histopathological results showed no sign of liver damage that occurred with proniosomal treatment. GB proniosomal formulations is a promising drug delivery system with good therapeutic efficacy and stability.

Protective Effects of Green Tea Supplementation against Lead-Induced Neurotoxicity in Mice.

The use of natural products as therapeutic agents is rapidly growing recently. In the current study, we investigated the protective effects of green tea supplementation on lead-induced toxicity in mice. Forty albino mice were divided into four groups as follows: A: control group; B: green tea receiving group; C: lead-intoxicated group; and D: lead-intoxicated group supplemented with green tea. At the end of the experiment, the animals were tested for neurobehavioral and biochemical alterations. Green tea was analyzed through Gas Chromatography-Mass Spectrometry (GC/MS) analysis. We found that supplementation with green tea ameliorated the lead-associated increase in body weight and blood glucose. Green tea supplementation also changed the blood picture that was affected due to lead toxicity and ameliorated lead-induced dyslipidemia. The group of mice that were supplemented with green tea has shown positive alterations in locomotory, anxiety, memory, and learning behaviors. The GC/MS analysis revealed many active ingredients among which the two most abundant were caffeine and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester. We concluded that green tea supplementation has several positive effects on the lead-induced neurotoxicity in mice and that these effects may be attributed to its main two active ingredients.

Box-Behnken Response Surface Design of Polysaccharide Extraction from Rhododendron arboreum and the Evaluation of Its Antioxidant Potential.

In the present investigation, the ultrasound-assisted extraction (UAE) conditions and optimization of Rhododendron arboreum polysaccharide (RAP) yield were studied by a Box-Behnken response surface design and the evaluation of its antioxidant potential. Three parameters that affect the productivity of UAE, such as extraction temperature (50-90 °C), extraction time (10-30 min), and solid-liquid ratio (1-2 g/mL), were examined to optimize the yield of the polysaccharide percentage. The chromatographic analysis revealed that the composition of monosaccharides was found to be glucose, galactose, mannose, arabinose, and fucose. The data were fitted to polynomial response models, applying multiple regression analysis with a high coefficient of determination value (R2 = 0.999). The data exhibited that the extraction parameters have significant effects on the extraction yield of polysaccharide percentage. Derringer's desirability prediction tool was attained under the optimal extraction conditions (extraction temperature 66.75 °C, extraction time 19.72 min, and liquid-solid ratio 1.66 mL/g) with a desirability value of 1 yielded the highest polysaccharide percentage (11.56%), which was confirmed through validation experiments. An average of 11.09 ± 1.65% of polysaccharide yield was obtained in optimized extraction conditions with a 95.43% validity. The in vitro antioxidant effect of polysaccharides of R. arboreum was studied. The results showed that the RAP extract exhibited a strong potential against free radical damage.

Stone quarrying induces organ dysfunction and oxidative stress in Meriones libycus.

Exposure to heavy metal-containing dust arising from stone quarrying may cause severe health problems. The aim of this study was to evaluate the impact of stone quarrying in Riyadh (Saudi Arabia) on the Libyan jird Meriones libycus. Soil samples and jirds were collected from four sites located at different distances from the quarrying area. Soil from the first (500 m away from the quarry) and second (1800 m away) sites showed a significant increase in cadmium (Cd), lead (Pb), nickel (Ni), and vanadium (V) when compared with the reference site (38,000 m away). Jirds at these sites exhibited significant increases in liver, kidney, lung, and fur levels of Cd, Pb, Ni, and V. Serum transaminases, creatinine, and malondialdehyde (MDA) levels were significantly increased in jirds, whereas reduced glutathione (GSH) levels decreased. Liver, kidney, and lung tissues of jirds, collected from the first and second sites, showed significantly increased MDA and decreased GSH levels. Additionally, animals at both sites showed altered hematological parameters and several histopathological changes in their liver, kidney, and lung. Soil and animals at the third site (7300 m away) showed no significant changes. Thus, our study showed the impact and hazardous effects of quarrying on the liver, kidney, lung, and hemogram of M. libycus. These findings can provide scientific evaluation for studying the impact of quarrying on the workers and communities living close to the studied area.

Oral administration of potassium bromate induces neurobehavioral changes, alters cerebral neurotransmitters level and impairs brain tissue of swiss mice.

BACKGROUND: Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. The present study reports the side effects of KBrO3 administration on the brain functions and behaviour of albino mice. METHODS: Animals were divided into three groups: control, low dose KBrO3 (100 mg/kg/day) and high dose KBrO3 (200 mg/kg/day) groups. RESULTS: Administration of KBrO3 led to a significant change in the body weight in the animals of the high dose group in the first, second and the last weeks while water consumption was not significantly changed. Neurobehavioral changes and a reduced Neurotransmitters levels were observed in both KBrO3 groups of mice. Also, the brain level of reduced glutathione (GSH) in KBrO3 receiving animals was decreased. Histological studies favoured these biochemical results showing extensive damage in the histological sections of brain of KBrO3-treated animals. CONCLUSIONS: These results show that KBrO3 has serious damaging effects on the central nervous system and therefore, its use should be avoided.

Effect of parsley (Petroselinum crispum, Apiaceae) juice against cadmium neurotoxicity in albino mice (Mus musculus).

BACKGROUND: Parsley was employed as an experimental probe to prevent the behavioral, biochemical and morphological changes in the brain tissue of the albino mice following chronic cadmium (Cd) administration. METHODS: Non-anesthetized adult male mice were given parsley juice (Petroselinum crispum, Apiaceae) daily by gastric intubation at doses of 10 and 20 g/kg/day. The animals were divided into six groups: Group A, mice were exposed to saline; Groups B and C, were given low and high doses of parsley juice, respectively; Group D, mice were exposed to Cd; Groups E and F, were exposed to Cd and concomitantly given low and high doses of parsley, respectively. RESULTS: Cd intoxication can cause behavioral abnormalities, biochemical and histopathological disturbances in treated mice. Parsley juice has significantly improved the Cd-associated behavioral changes, reduced the elevation of lipid peroxidation and normalized the Cd effect on reduced glutathione and peroxidase activities in the brain of treated mice. Histological data have supported these foundations whereas Cd treatment has induced neuronal degeneration, chromatolysis and pyknosis in the cerebrum, cerebellum and medulla oblongata. CONCLUSION: The low dose (5 g/kg/day) of parsley exhibited beneficial effects in reducing the deleterious changes associated with Cd treatment on the behavior, neurotransmitters level, oxidative stress and brain neurons of the Cd-treated mice.

Neurochemical, structural and neurobehavioral evidence of neuronal protection by whey proteins in diabetic albino mice.

BACKGROUND: Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (CNS) and alterations in oxidative stress. The aim of this study was to determine whether dietary supplement with whey protein (WP) could improve neurobehavior, oxidative stress and neuronal structure in the CNS. METHODS: Animals were distributed in three groups, a control group (N), a diabetic mellitus group (DM) and a DM group orally supplemented with WP (WP). RESULTS: The DM group of animals receiving WP had reduced blood glucose, significantly decreased free radical Diphenyl-picrylhydrazyl (DPPH) and lower lipid peroxidation in brain tissue. The WP group of animals showed improvement in balancing, coordination and fore-limb strength, oxidative stress and neuronal structure. CONCLUSION: The results of this study show that dietary supplementation with WP reduced oxidative stress, protected CNS neurons and improved the neurobehavior of diabetic mice.

Enhanced removal of bisphenol S in ozone/peroxymonosulfate system: Kinetics, intermediates and reaction mechanism.

The degradation process of bisphenol S (BPS) in ozone/peroxymonosulfate (O3/PMS) system was systematically explored. The results showed that the removal efficiency of BPS by O3 could be significantly improved with addition of PMS. Compared with ozonation alone, the pseudo-first-order constant (kobs) was increased by 2-5 times after adding 400 µM PMS. In O3/PMS system, accelerated removal of BPS was observed under neutral and alkaline conditions. The removal efficiency of BPS reached 100% after 40 s of reaction at pH 7.0, with the kobs of 0.098 s-1. Moreover, Cu2+ had a catalytic effect on the O3/PMS system, because it could catalyze the decomposition of ozone and PMS to produce •OH and SO4•-, respectively. Electron paramagnetic resonance illustrated that •OH and SO4•- were the reactive species in O3/PMS system. Twelve intermediates were identified by mass spectrometry, and the degradation reactions in O3/PMS system mainly included hydroxylation, sulfate addition, polymerization and ß-scission. Finally, the toxicity of the products was evaluated by the EOCSAR program. Our results introduce an efficient method for BPS removal and would provide some guidance for the development of O3-based advanced oxidation technology.

Assessment of the UV/DCCNa and UV/NaClO oxidation process for the removal of diethyl phthalate (DEP) in the aqueous system.

In this work, the removal and transformation process of diethyl phthalate (DEP) in UV/dichloroisocyanurate (UV/DCCNa) and UV/sodium hypochlorite (UV/NaClO) systems were compared to evaluate the application potential of UV/DCCNa technology. Compared with UV/NaClO, UV/DCCNa process has the advantage of DEP removal and caused a higher degradation efficiency (93.8%) within 45 min of oxidation in ultrapure water due to the sustained release of hypochloric acid (HOCl). Fourteen intermediate products were found by high-resolution mass spectrometry, and the transformation patterns including hydroxylation, hydrolysis, chlorination, cross-coupling, and nitrosation were proposed. The oxidation processes were also performed under quasi-realistic environmental conditions, and it was found that DEP could be effectively removed in both systems, with yields of disinfection byproduct meeting the drinking water disinfection standard (<60.0 µg/L). Comparing the single system, the removal of DEP decreased in the mixed system containing five kinds of PAEs, which could be attributed to the regeneration of DEP and the competitive effect of •OH occurred among the Dimethyl phthalate (DMP), DEP, Dipropyl phthalate (DPrP), Diallyl phthalate (DAP) and Diisobutyl phthalate (DiBP). However, a greater removal performance presented in UV/DCCNa system compared with UV/NaClO system (69.4% > 62.1%). Further, assessment of mutagenicity and developmental toxicity by Toxicity Estimation Software Tool (T.E.S.T) software indicated that UV/DCCNa process has fewer adverse effects on the environment and is a more environmentally friendly chlorination method. This study may provide some guidance for selecting the suitable disinfection technology for drinking water treatment.

Anticoccidial and Antioxidant Activities of an Ethanolic Extract of Teucrium polium Leaves on Eimeria papillate-Infected Mice.

Eimeria spp. are responsible for the economic loss of both domestic and wild animals due to coccidiosis, the most common parasitic disease. The resistance to currently available drugs used to treat coccidiosis has been proven. Medicinal plants that contain physiologically active phytochemicals have been widely used in traditional medicine. Teucrium polium leaf extract (TPLE) has been shown to exhibit pharmacological, antioxidant, and anticoccidial properties in different experiments. Here, our investigation focused on how T. polium leaf extract affected the way that Eimeria papillate caused intestinal injury in mice. Thirty-five male Swiss albino mice were divided into seven groups, as follows: group I: untreated and uninfected (negative control); group II: uninfected, treated group with TPLE (150 mg/kg b.w); and group III: infected untreated (positive control). Groups III-VII were orally administered 103 sporulated E. papillata oocysts. A total of 60 min after infection, groups IV-VI were treated for five successive days with 50, 150, and 250 mg/kg b.w TPLE, respectively, while group VII was treated with amprolium (120 mg/kg b.w.). The mice had been euthanized on the fifth day post-infection, and the jejunum tissues were prepared for histology and oxidative stress studies. A total of 150 mg/kg of TPLE was the most effective dosage, significantly decreasing oocyst output by about 80.5%, accompanied by a significant reduction in the number of developmental parasitic phases in jejunal sections. In addition, the decrease in the number of goblet cells in the jejuna of mice raised after treatment. Also, TPLE greatly diminished the body weight loss of infected mice. Moreover, our research proved that TPLE reduced oxidative damage due to E. papillata infection via decreasing intestinal malondialdehyde (MDA) and nitric oxide (NO) levels and increasing reduced superoxide dismutase (SOD) and glutathione (GSH) levels. These results demonstrated that TPLE had potent anticoccidial properties. TPE's efficacy as a natural antioxidant has also been demonstrated in reducing oxidative stress and enhancing antioxidant systems to mitigate biochemical and histological changes in the jejunum caused by E. papillata.

Oral administration of proniosomal glibenclamide formulation protects testicular tissue from hyperglycemia fluctuations and ROS via Nrf2/HO-1 pathway.

Type 2 diabetes causes high blood sugar due to insulin malfunction and is linked to male infertility. Using proniosomes can enhance the effectiveness of Glibenclamide, a medication that stimulates insulin secretion. In our study, male rats with diabetes were treated with GLB with or without proniosomal for 14 days. Proniosomal formulations maintained glucose levels prevented weight loss and showed normal testicular tissue. GLB-proniosomal reduces ROS caused by T2DM through Nrf2, HO-1 pathway and increases CAT, SOD, and GSH production in response to insulin and glucose uptake. The reference and proniosomal treatments showed CAT and SOD significant enzymatic elevation compared to the positive and negative control. CAT significantly correlated with Gpx4 expression with P = 0.0169 and r = 0.98; similarly, the enzymatic activity of SOD also showed a positive correlation between the average glucose levels (r = 0.99 and P = 0.0037). Intestinally, GSH analysis revealed that only proniosomal-GLB samples are significantly elevated from the positive control, with a P value of 0.0210. The data showed proniosomal-GLB was more effective than pure GLB, confirmed by higher Nrf2 (2.050 folds), HO-1 (2.148 folds), and GPx4 (1.9 folds) transcript levels relative to the control with less sample diversity compared to the reference samples, indicating proniosomal stabilized GLB in the blood. Administering GLB and proniosomes formulation has effectively restored testicular function and sperm production in diabetic rats by regulating ROS levels and upregulating anti-ROS in response to glucose uptake. These findings may lead to better treatments for diabetic patients who have infertility issues.

Degradation of Butylated Hydroxyanisole by the Combined Use of Peroxymonosulfate and Ferrate(VI): Reaction Kinetics, Mechanism and Toxicity Evaluation.

Butylated hydroxyanisole (BHA), a synthetic phenolic antioxidant (SPA), is now widely present in natural waters. To improve the degradation efficiency of BHA and reduce product toxicity, a combination of peroxymonosulfate (PMS) and Ferrate(VI) (Fe(VI)) was used in this study. We systematically investigated the reaction kinetics, mechanism and product toxicity in the degradation of BHA through the combined use of PMS and Fe(VI). The results showed that PMS and Fe(VI) have synergistic effects on the degradation of BHA. The effects of operational factors, including PMS dosage, pH and coexisting ions (Cl-, SO42-, HCO3-, K+, NH4+ and Mg2+), and different water matrices were investigated through a series of kinetic experiments. When T = 25 °C, the initial pH was 8.0, the initial BHA concentration was 100 µM, the initial concentration ratio of [PMS]0:[Fe(VI)]0:[BHA]0 was 100:1:1 and the degradation rate could reach 92.4% within 30 min. Through liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) identification, it was determined that the oxidation pathway of BHA caused by PMS/Fe(VI) mainly includes hydroxylation, ring-opening and coupling reactions. Density functional theory (DFT) calculations indicated that •OH was most likely to attack BHA and generate hydroxylated products. The comprehensive comparison of product toxicity results showed that the PMS/Fe(VI) system can effectively reduce the environmental risk of a reaction. This study contributes to the development of PMS/Fe(VI) for water treatment applications.

Sodium alginate-modified alkali-activated eggshell/Fe3O4 nanoparticles: A magnetic bio-based spherical adsorbent for cationic dyes adsorption.

Herein, a mixture of eggshell (ES) and magnetite nanoparticles (MNPs) was alkali-activated using NaOH/Na2SiO3 solution and then, impregnated with sodium alginate (SA) to prepare a magnetic bio-based adsorbent (namely SAAES/SA/MNPs) for the decontamination of water containing basic dyes, in particular, methylene blue (MB) and crystal violet (CV). The physicochemical properties of magnetic spheres of SAAES/SA/MNPs were characterized using XRD, FTIR, FESEM, EDX, elemental mapping, TEM, and zeta potential techniques. Dye adsorption equilibrium was studied experimentally at pH 8.0 and 25-55 °C, and a statistical physics multilayer model was applied to understand the removal mechanism of these dyes including the adsorption orientations on the adsorbent surface. The number of adsorbed dye molecules per functional group (n) of this bio-based adsorbent ranged from 0.70 to 0.91, indicating the presence of vertical and horizontal adsorption orientations for these organic molecules at all tested solution temperatures. The calculated saturation adsorption capacities (Qsat) were 332.57-256.62 mg/g for CV and 304.47-240.62 mg/g for MB, and an exothermic adsorption was observed for both adsorbates. The estimated adsorption energies (∆E) were < 25 kJ/mol, confirming that the SAAES/SA/MNPs-dye interactions were governed by physical forces as electrostatic interactions. This bio-based adsorbent was effectively regenerated using ethanol and it can be reused showing a removal of 71 and 74 % of MB and CV, respectively, after fourth adsorption-desorption cycles. Overall, the results of this article suggest the attractive performance of SAAES/SA/MNPs for removing basic dyes from aqueous solutions, thus highlighting the promising potential of this magnetic bio-based adsorbent for sustainable wastewater treatment at an industrial level.

Determination of dose- and time-dependent hepatotoxicity and apoptosis of Lanthanum oxide nanoparticles in female Swiss albino mice.

Nanosized lanthanum oxide particles (La2O3) are commonly utilized in various industries. The potential health risks associated with La2O3 nanoparticles, cytotoxic effects at varying doses and time intervals, and the mechanisms behind their induction of behavioral changes remain uncertain and necessitate further investigation. Therefore, this study examined in vivo hepatotoxicity, considering the quantity (60, 150, and 300 mg/kg) and time-dependent induction of reactive oxygen species (ROS) over one week or 21 days. The mice received intraperitoneal injections of three different concentrations in Milli-Q water. Throughout the experiments, no physical changes or weight loss were observed among the groups. However, after 21 days, only the highest concentration showed signs of anxiety in the activity cage (p < 0.05). Subsequently, all animals treated with La2O3 NPs exhibited a significant loss of learning and memory recall using the Active Avoidances test, after 21 days (p < 0.001). Markers for anti-reactive oxygen species (ROS) such as superoxide dismutase (SOD) were significantly upregulated in response to all concentrations of NPs after seven days compared to the control group. This was confirmed by a significant increase in glutathione peroxidase (Gpx1) and pro-apoptotic Caspase-3 expression at the lowest and highest doses. Additionally, both transcription and protein levels of the anti-apoptotic BCL-2 surpassed P53 protein in a dosage-dependent manner, indicating activation of the primary anti-apoptosis pathway. After 21 days, P53 levels exceeded BCL-2 protein levels, confirming a significant loss of BCL-2 mRNA, particularly at the 300 mg/kg concentration. Furthermore, a higher transcription level of Caspase-3, SOD, and Gpx1 was observed, with the highest values detected at the 300 mg/kg concentration, indicating the activation of cell death. Histopathological analysis of the liver illustrated apoptotic bodies resulting from La2O3 NP concentration. The investigation revealed multiple inflammatory foci, cytoplasmic degeneration, steatosis, and DNA fragmentation consistent with increased damage over time due to higher concentrations. Blood samples were also analyzed to determine liver enzymatic changes, including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), and lipid profiles. The results showed significant differences among all La2O3 NP concentrations, with the most pronounced damage observed at the 300 mg/kg dose even after 21 days. Based on an animal model, this study suggests that La2O3 hepatotoxicity is likely caused by the size and shape of nanoparticles (NPs), following a dose and time-dependent mechanism that induces the production of reactive oxygen species and behavioral changes such as anxiety and memory loss.

In vitro studies for antiparasitic activities of Punica granatum extract.

Because of the drug resistance, medicinal plants are used more frequently than coccidiostats to treat and control coccidiosis. Punica granatum is a powerful antioxidant with a variety of medicinal uses. This study used an in vitro experiment to investigate how different P. granatum from Yemen (Y) and Egypt (E) sources affected oocyst sporulation and served as an anthelminthic effector. In contrast to PGE and mebendazole, PGY (200 mg/mL) has the shortest time to paralyze and death the earthworm Eisenia fetida in this investigation. In addition, the treated worm groups' cuticle thickness and shrinkage in comparison to the control group were assessed and contrasted. Eimeria papillata is used as a model protozoan parasite in anticoccidial assays. This study shows that P. granatum affects oocysts sporulation in a dose-dependent manner, with maximal percentages of 100% (PGY) and 48.60% (PGE) at 96 h for P. granatum concentrations of 200 mg/mL. Inhibition (%) was compared to various detergents, as well as positive and negative controls. According to our research, the P. granatum extract had powerful anthelmintic and anticoccidial properties, with the potency changing according to the environmental conditions of each fruit source. RESEARCH HIGHLIGHTS: Habitat of the plant is useful for production and accumulation of some secondary metabolites in plants which be effective for the therapeutic uses. Different parameters in the environmental ecosystem affecting variation in chemical compositions and biological activity of P. granatum.

Impact of petroleum industry on goats in Saudi Arabia: heavy metal accumulation, oxidative stress, and tissue injury.

Heavy metals (HMs) constitute a group of persistent toxic pollutants, and the petroleum industry is one of the sources of these metals. This study aimed to evaluate the levels of lead (Pb), cadmium (Cd), nickel (Ni), and vanadium (V) in Plantago ovata and milk and tissues of domestic goats in the eastern region of Saudi Arabia. Plant samples and blood, milk, muscle, liver, and kidney samples were collected from domestic goats and the levels of Pb, Cd, V, and Ni were determined. Liver and kidney tissue injury, oxidative stress, and expression of pro-inflammatory and apoptosis markers were evaluated. Pb, Cd, V, and Ni were increased in Plantago ovata as well as in milk, blood, muscle, liver, and kidney of goats collected from the polluted site. Aminotransferases, creatinine, and urea were increased in serum, and histopathological changes were observed in the liver and kidney of goats at the oil extraction site. Malondialdehyde and the expression levels of pro-inflammatory cytokines, Bax, and caspase-3 were increased, whereas cellular antioxidants and Bcl-2 were decreased in liver and kidney of goats at the polluted site. In conclusion, petroleum industry caused liver and kidney injury, oxidative stress, and upregulated pro-inflammatory and apoptosis markers in goats. These findings highlight the negative impact of petroleum industry on the environment and call attention to the assessment of its effect on the health of nearby communities.

In vivo anticoccidial, antioxidant, and anti-inflammatory activities of avocado fruit, Persea americana (Lauraceae), against Eimeria papillata infection.

Apicomplexan parasites, especially Eimeria sp., are the main intestinal murine pathogens, that lead to severe injuries to farm and domestic animals. Many anticoccidial drugs are available for coccidiosis, which, leads to the development of drug-resistant parasites. Recently, natural products are considered as an alternative agent to control coccidiosis. This study was designed to evaluate the anticoccidial activity of the Persea americana fruit extract (PAFE) in male C57BL/6 mice. A total of 35 male mice were divided into seven equal groups (1, 2, 3, 4, 5, 6, and 7). At day 0, all groups except the first group which served as uninfected-untreated control were infected orally with 1 × 103E. papillata sporulated oocysts. Group 2 served as uninfected-treated control. Group 3 was considered an infected-untreated group. After 60 min of infection, groups 4, 5, and 6 were treated with oral doses of PAFE aqueous methanolic extract (100, 300, and 500 mg/kg of body weight, respectively). Group 7 was treated with amprolium (a reference drug for coccidiosis). PAFE with 500 mg/kg, was the most effective dose, inducing a significant reduction in the output of oocysts in mice feces (by about 85.41%), accompanied by a significant decrease in the number of the developmental parasite stages and a significant elevation of the goblet cells in the jejunal tissues. Upon treatment, a significant change in the oxidative status due to E. papillata infection was observed, where the levels of glutathione (GSH) increased, while, levels of malondialdehyde (MDA) and nitric oxide (NO) were decreased. In addition, the infection significantly upregulated the inflammatory cytokines of interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ). This increase in mRNA expression of IL-1ß, TNF-α, and IFN-γ was about 8.3, 10.6, and 4.5-fold, respectively, which significantly downregulated upon treatment. Collectively, P. americana is a promising medicinal plant with anticoccidial, antioxidant, and anti-inflammatory activities and could be used for the treatment of coccidiosis.

Streptomyces Bioactive Metabolites Prevent Liver Cancer through Apoptosis, Inhibiting Oxidative Stress and Inflammatory Markers in Diethylnitrosamine-Induced Hepatocellular Carcinoma.

A safe and effective treatment for liver cancer is still elusive despite all attempts. Biomolecules produced from natural products and their derivatives are potential sources of new anticancer medications. This study aimed to investigate the anticancer potential of a Streptomyces sp. bacterial extract against diethylnitrosamine (DEN)-induced liver cancer in Swiss albino mice and explore the underlying cellular and molecular mechanisms. The ethyl acetate extract of a Streptomyces sp. was screened for its potential anticancer activities against HepG-2 using the MTT assay, and the IC50 was also determined. Gas chromatography-mass spectrometric analysis was used to identify the chemical constituents of the Streptomyces extract. Mice were administered DEN at the age of 2 weeks, and from week 32 until week 36 (4 weeks), they received two doses of Streptomyces extract (25 and 50 mg/kg body weight) orally daily. The Streptomyces extract contains 29 different compounds, according to the GC-MS analysis. The rate of HepG-2 growth was dramatically reduced by the Streptomyces extract. In the mice model. Streptomyces extract considerably lessened the negative effects of DEN on liver functions at both doses. Alpha-fetoprotein (AFP) levels were significantly (p < 0.001) decreased, and P53 mRNA expression was increased, both of which were signs that Streptomyces extract was suppressing carcinogenesis. This anticancer effect was also supported by histological analysis. Streptomyces extract therapy additionally stopped DEN-induced alterations in hepatic oxidative stress and enhanced antioxidant activity. Additionally, Streptomyces extract reduced DEN-induced inflammation, as shown by the decline in interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) levels. Additionally, the Streptomyces extract administration dramatically boosted Bax and caspase-3 levels while decreasing Bcl-2 expressions in the liver according to the Immunohistochemistry examination. In summary, Streptomyces extract is reported here as a potent chemopreventive agent against hepatocellular carcinoma through multiple mechanisms, including inhibiting oxidative stress, cell apoptosis, and inflammation.