Fenpropathrin provoked kidney damage via controlling the NLRP3/Caspase-1/GSDMD-mediated pyroptosis: The palliative role of curcumin-loaded chitosan nanoparticles.

This study assessed the ability of formulated curcumin-loaded chitosan nanoparticles (CU-CS-NPs) to reduce the kidney damage resulting from fenpropathrin (FPN) in rats compared to curcumin (CU) in rats. Sixty male Sprague Dawley rats were separated into six groups and orally administered 1 mL/kg b.wt corn oil, 50 mg CU/kg b.wt, 50 mg CU-CS-NPs /kg b.wt., 15 mg FPN /kg b.wt, CU+ FPN or CU-CS-NPs + FPN for 60 days. Then, serum renal damage products were assessed. Total antioxidant capacity, reactive oxygen species, interleukin 1ß (IL-1ß), malondialdehyde, NF-κB P65, cleaved-Caspase-1, and Caspase-8 were estimated in kidney homogenates. The cleaved Caspase-3 and TNF-α immunoexpression and pyroptosis-related genes were determined in renal tissues. The results showed that CU-CS-NPS significantly repressed the FPN-induced increment in kidney damage products (urea, uric acid, and creatinine). Moreover, the FPN-associated hypo-proteinemia, renal oxidative stress and apoptotic reactions, and impaired renal histology were considerably repaired by CU and CU-CS-NPs. Additionally, compared to FPN-exposed rats, CU, and CU-CS-NPs-treated rats had considerably lower immunoexpression of cleaved Caspase-3 and TNF-α in renal tissue. The pyroptosis-related genes NLRP3, GSDMD, IL-18, Caspase-3, Caspase-1, IL-1ß, Caspase-8, TNF-α, and NF-κB dramatically upregulated by FPN exposure in the renal tissues. Yet, in CU and CU-CS-NPs-treated rats, the gene above expression deviations were corrected. Notably, CU-CS-NPs were superior to CU in preventing oxidative damage and inflammation and regulating pyroptosis in the renal tissues of the FPN-exposed group. The results of the present study conclusively showed the superior favorable effect of CU-CS-NPs in counteracting renal impairment linked to environmental pollutants.

Attenuation of Streptozotocin-Induced Diabetic Neuropathic Allodynia by Flavone Derivative Through Modulation of GABA-ergic Mechanisms and Endogenous Biomarkers.

Diabetic neuropathic pain is one of the most devasting disorders of peripheral nervous system. The loss of GABAergic inhibition is associated with the development of painful diabetic neuropathy. The current study evaluated the potential of 3-Hydroxy-2-methoxy-6-methyl flavone (3-OH-2'MeO6MF), to ameliorate peripheral neuropathic pain using an STZ-induced hyperglycemia rat model. The pain threshold was assessed by tail flick, cold, mechanical allodynia, and formalin test on days 0, 14, 21, and 28 after STZ administration accompanied by evaluation of several biochemical parameters. Administration of 3-OH-2'-MeO6MF (1,10, 30, and 100 mg/kg, i.p) significantly enhanced the tail withdrawal threshold in tail-flick and tail cold allodynia tests. 3-OH-2'-MeO6MF also increased the paw withdrawal threshold in mechanical allodynia and decreased paw licking time in the formalin test. Additionally, 3-OH-2'-MeO6MF also attenuated the increase in concentrations of myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), nitrite, TNF-α, and IL 6 along with increases in glutathione (GSH). Pretreatment of pentylenetetrazole (PTZ) (40 mg/kg, i.p.) abolished the antinociceptive effect of 3-OH-2'-MeO6MF in mechanical allodynia. Besides, the STZ-induced alterations in the GABA concentration and GABA transaminase activity attenuated by 3-OH-2'-MeO6MF treatment suggest GABAergic mechanisms. Molecular docking also authenticates the involvement of α2ß2γ2L GABA-A receptors and GABA-T enzyme in the antinociceptive activities of 3-OH-2'-MeO6MF.

The Effect of Cerebrolysin in an Animal Model of Forebrain Ischemic-Reperfusion Injury: New Insights into the Activation of the Keap1/Nrf2/Antioxidant Signaling Pathway.

Forebrain ischemia-reperfusion (IR) injury causes neurological impairments due to decreased cerebral autoregulation, hypoperfusion, and edema in the hours to days following the restoration of spontaneous circulation. This study aimed to examine the protective and/or therapeutic effects of cerebrolysin (CBL) in managing forebrain IR injury and any probable underlying mechanisms. To study the contribution of reperfusion to forebrain injury, we developed a transient dual carotid artery ligation (tDCAL/IR) mouse model. Five equal groups of six BLC57 mice were created: Group 1: control group (no surgery was performed); Group 2: sham surgery (surgery was performed without IR); Group 3: tDCAL/IR (surgery with IR via permanently ligating the left CA and temporarily closing the right CA for 30 min, followed by reperfusion for 72 h); Group 4: CBL + tDCAL/IR (CBL was given intravenously at a 60 mg/kg BW dose 30 min before IR); and Group 5: tDCAL/IR + CBL (CBL was administered i.v. at 60 mg/kg BW three hours after IR). At 72 h following IR, the mice were euthanized. CBL administration 3 h after IR improved neurological functional recovery, enhanced anti-inflammatory and antioxidant activities, alleviated apoptotic neuronal death, and inhibited reactive microglial and astrocyte activation, resulting in neuroprotection after IR injury in the tDCAL/IR + CBL mice group as compared to the other groups. Furthermore, CBL reduced the TLRs/NF-kB/cytokines while activating the Keap1/Nrf2/antioxidant signaling pathway. These results indicate that CBL may improve neurologic function in mice following IR.

Total Polyphenols Content, Antioxidant and Antimicrobial Activities of Leaves of Solanum elaeagnifolium Cav. from Morocco.

Solanum elaeagnifolium is among the invasive plants of Morocco; studies on its chemical composition and biological activities are few in number in Morocco. S. elaeagnifolium has shown molluscicidal and nematicidal and cancer-inhibitory effects, anti-inflammatory, analgesic activity, and antibacterial activity. The objective of this research is to improve this plant and assess its antibacterial and antioxidant properties as well as its total polyphenolic content (TPC) and total flavonoid content (TFC). The Folin-Ciocalteu method and the aluminium-trichloride method were used to determine TPC and TFC in hydro-ethanolic (HEE) and hydro-acetonic (HAE) leaf extract. Three assays were performed to determine the antioxidant activity: the DPPH test (radical 2,2'-diphenyl-1-picrylhydrazyl), the FRAP test (Ferric Reducing Antioxidant Power), and the TAC test. Disk diffusion and microdilution were used to test antibacterial activity against four pathogenic bacteria and Candida albicans. The hydro-ethanolic extract 2.54 ± 0.4 mg EAG/g has a greater polyphenol concentration than the hydro-acetonic extract 1.58 ± 0.03 mg EAG/g. Although the flavonoid content of the hydro-acetonic extract (0.067 ± 0.001 mg EQ/g) is larger than that of the hydro-ethanolic extract (0.012 ± 0.001 mg EQ/g), the flavonoid content of the hydro-ethanolic extract (0.012 ± 0.001 mg EQ/g). The DPPH values were IC-50 = 0.081 ± 0.004 mg/mL for hydro-ethanoic extract and 0.198 ± 0.019 mg/mL for hydro-acetonic extract, both extracts superior to BHT (0.122 ± 0.021 g/mL). While the FRAP assay showed a low iron-reducing power values for both extracts compared to BHT), the overall antioxidant activity of the two extracts was found to be considerable. The overall antioxidant activity of the hydro-ethanolic extract was 8.95 ± 0.42 mg EAA/g, whereas the total antioxidant activity of the hydro-acetonic extract was 6.44 ± 0.61 mg EAA/g. In comparison with the antibiotic Erythromycin, HAE and HEE from S. elaeagnifolium leaves demonstrated significant antibacterial action. HAE had the best inhibitory efficacy against Bacillus subtilis DSM 6333, with an inhibition diameter of 10.5 ± 0.50 mm and a MIC of 7.5 ± 0.00 mg/mL, as well as against Proteus mirabilis ATCC 29906, with an inhibitory diameter of 8.25 ± 0.75 mm and a MIC of 15 ± 0.00 mg/mL.

Potential therapeutic effects of avenanthramide-C against lung toxicity caused by silver nanoparticles injection in rats.

Most clinical investigations about the impact of nanoparticles on cells and tissues show that nanoparticles may enter the human body by means of respiratory tracts. Humans, animals, plants and environments are continually presented to a wide scope of business items containing silver nanoparticles (Ag NPs) in their piece. Ag NPs, utilized in various consumer products as room showers, surface cleaners, wound dressings, food storage containers and many textiles. The current examination planned to explore the defensive role of Avenanthramide-C (Avns) contrary to the lung toxicity initiated by Ag NPs injection in rats. 40 male Wistar rats were separated into 4 groups (Gp1, control; Gp2, Avns; Gp3, Ag NPs; Gp4, Ag NPs+Avns). Current results revealed that; Ag NPs induced a significant depletion in RBCs count, hemoglobin, platelets counts and a significant increase in total WBCs, lung injury, cyclooxygenase-2 (COX2) and TNFα expressions as compared to control. Treatments of Ag NPs with Avenanthramide-C extract (Ag NPs+Avns) improved the lung structure and blood complete pictures as compared to Ag NPs group.

Therapeutic Uses of Red Macroalgae.

Red Seaweed "Rhodophyta" are an important group of macroalgae that include approximately 7000 species. They are a rich source of structurally diverse bioactive constituents, including protein, sulfated polysaccharides, pigments, polyunsaturated fatty acids, vitamins, minerals, and phenolic compounds with nutritional, medical, and industrial importance. Polysaccharides are the main components in the cell wall of red algae and represent about 40-50% of the dry weight, which are extensively utilized in industry and pharmaceutical compounds, due to their thickening and gelling properties. The hydrocolloids galactans carrageenans and agars are the main red seaweed cell wall polysaccharides, which had broad-spectrum therapeutic characters. Generally, the chemical contents of seaweed are different according to the algal species, growth stage, environment, and external conditions, e.g., the temperature of the water, light intensity, nutrient concentrations in the ecosystem. Economically, they can be recommended as a substitute source for natural ingredients that contribute to a broad range of bioactivities like cancer therapy, anti-inflammatory agents, and acetylcholinesterase inhibitory. This review touches on the main points of the pharmaceutical applications of red seaweed, as well as the exploitation of their specific compounds and secondary metabolites with vital roles.

Rheumatoid Arthritis Treatment Potential of Stearic Acid Nanoparticles of Quercetin in Rats.

This study aims to assess the anti-inflammatory potential of stearic acid nanoparticles of quercetin in an arthritic rat model. This article describes the fabrication of solid lipid nanoparticles (SLNs) using the hot melt encapsulation method, followed by the anti-inflammatory study of SLNs and other characterizations such as FTIR, XRD, and SEM. Thirty male healthy albino rats were taken and treated with FCA to induce rheumatoid arthritis. Quercetin loading of quercetin to stearic acid was confirmed by FTIR. The efficacy of quercetin-loaded SLNs to reduce inflammation was evaluated with the help of inflammatory biomarker levels. Quercetin-loaded stearic acid nanoparticles were successfully prepared by using a hot melt encapsulation method. Their average size and zeta potential were 100 nm and -25 mV, respectively. Rheumatoid arthritis was significantly (p < 0.001) reduced in the quercetin-loaded SLN group, as indicated by finding out the reduced levels of inflammatory mediators such as tumor necrosis factor (TNF-α) and rheumatoid factor. Quercetin-loaded stearic acid nanoparticles were found to be potentially effective in treating RA.

Unveiling the altered metabolic pathways induced by nivolumab in non-small cell lung cancer via GC-MS metabolomics approach coupled with multivariate analysis.

This research investigates the effects of the immunotherapeutic agent nivolumab on the metabolism of lung cancer cells (NCI-H1975) using GC-MS metabolomic profiling. Multivariate analysis such as unsupervised PCA and supervised OPLS-DA along with univariate analysis and pathway analysis were employed to explore the metabolomic data and identify altered metabolic pathways induced by nivolumab treatment. The study revealed distinct metabolic alterations in cancer cells, linked to proliferative and survival advantages, such as enhanced glycolysis, increased glutaminolysis, and modified amino acid metabolism. Key findings indicate elevated levels of glycolysis-related metabolites (glycine, alanine, pyruvate, and lactate) and TCA cycle intermediates (succinate, fumarate, malate) in cancer cells, with a significant decrease following nivolumab treatment. Additionally, lower levels of aspartic acid and citrate in cancer cells imply altered nucleotide synthesis and fatty acid production essential for tumor growth. Treatment with nivolumab also reduced oleic acid levels, indicative of its effect on disrupted lipid metabolism. Our research shows nivolumab's potential to modify metabolic pathways involved in lung cancer progression, suggesting its dual role in cancer therapy: as an immune response modulator and a metabolic pathway disruptor.

Therapeutic implications of dapagliflozin on the metabolomics profile of diabetic rats: A GC-MS investigation coupled with multivariate analysis.

BACKGROUND: Diabetes mellitus is a complex metabolic disorder with systemic implications, necessitating the search for reliable biomarkers and therapeutic strategies. This study investigates the metabolomics profile alterations in diabetic rats, with a focus on the therapeutic effects of Dapagliflozin, a drug known to inhibit renal glucose reabsorption, using Gas Chromatography-Mass Spectrometry analysis. METHODS: A GC-MS based metabolomics approach combined with multivariate and univariate statistical analyses was utilized to study serum samples from a diabetic model of Wistar rats, treated with dapagliflozin. Metabolomics pathways analysis was also performed to identify the altered metabolic pathways associated with the disease and the intervention. RESULTS: Dapagliflozin treatment in diabetic rats resulted in normalized levels of metabolites associated with insulin resistance, notably branched-chain and aromatic amino acids. Improvements in glycine metabolism were observed, suggesting a modulatory role of the drug. Additionally, reduced palmitic acid levels indicated an alleviation of lipotoxic effects. The metabolic changes indicate a restorative effect of dapagliflozin on diabetes-induced metabolic perturbations. CONCLUSIONS: The comprehensive metabolomics analysis demonstrated the potential of GC-MS in revealing significant metabolic pathway alterations due to dapagliflozin treatment in diabetic model rats. The therapy induced normalization of key metabolic disturbances, providing insights that could advance personalized diabetes mellitus management and therapeutic monitoring, highlighting the utility of metabolomics in understanding drug mechanisms and effects.

Development of Poly(vinyl alcohol)-Chitosan Composite Nanofibers for Dual Drug Therapy of Wounds.

Current trends in localized drug delivery are emphasizing the development of dual drug-loaded electrospun nanofibers (NFs) for an improved therapeutic effect on wounds, especially infected skin wounds. The objective of this study was to formulate a new healing therapy for an infected skin wound. To achieve this goal, this study involved the development and characterization of poly(vinyl alcohol) (PVA)/chitosan nanofibers loaded with ciprofloxacin and rutin hydrate. Polymers and drugs were used in different ratios. Nanofiber morphology was studied by scanning electron microscopy, thermal stability by thermogravimetric analysis, structural determination by the X-ray diffraction method, and integrity by Fourier transform infrared spectroscopy. Dissolution studies were performed to check the drug release behavior of the formulations. Antibacterial studies were performed against Staphylococcus aureus and Pseudomonas aeruginosa. The wound healing efficiency of dual drug-loaded nanofibers was measured by a full-thickness excisional wound model of rabbits. The fabricated nanofibers were smooth in morphology. According to FTIR findings, the drugs remained intact in the nanofibers. The results of swelling ratio and porosity revealed that the pore size was increased as the amount of chitosan was increased up to 30% but a further increase in chitosan concentration reduced the swelling ratio and porosity. Drug release studies of nanofibers depicted an initial burst effect and afterward controlled drug release behavior. Drug-loaded nanofibers showed better activity against S. aureus than P. aeruginosa. The antibacterial efficacy of rutin hydrate with ciprofloxacin was improved compared to that of the formulation having rutin hydrate only, likely due to the additive effect in activity. Based on wound healing studies, nanofibrous membranes acted as a promising wound dressing material as compared to the commercial wound healing formulation. Drug-loaded polymeric nanofibers were successfully fabricated by using an electrospinning method. These nanofibers showed an efficient ability to deliver drugs and treat infected wounds.

Nigella sativa oil restores hormonal levels, and endocrine signals among thyroid, ovarian, and uterine tissues of female Wistar rats following sodium fluoride toxicity.

The current study aimed to explore the possible prophylactic and therapeutic effect of Nigella sativa L. oil (NSO) against disruption of endocrine signals and injuries in the thyroid gland, ovary, and uterine tissues induced by sodium fluoride (NaF). Twenty-eight mature female Wistar rats were randomly allocated into four experimental groups (n = 7/group) as follows: control group; NaF group, orally received NaF (20 mg/kg b.wt.) daily; NSO/NaF, orally received NSO (300 mg/kg b.wt.) two weeks before being given NaF and continued throughout the experiment; and NSO+NaF group orally received NSO concurrently with NaF. Our results indicated that NSO restored hormonal balance and suppressed oxidative damage and inflammation. Moreover, the levels of triiodothyronine, thyroxine, thyroid peroxidase, estrogen (E2), progesterone, follicle-stimulating hormone, and luteinizing hormone were elevated, while prostaglandins F2-α and cortisol levels were decreased in NSO treated groups compared to NaF-intoxicated rats. As well, NSO significantly boosted levels of antioxidant molecules, and lowered lipid peroxidation of examined tissues, unlike NaF-treated group. NSO also up-regulated antioxidant enzymes, anti-apoptotic protein, zona pellucida sperm-binding protein, bone morphogenetic protein, and thyroid stimulating hormone, conversely down-regulated inflammatory cytokines, apoptotic proteins, estrogen receptor-α, estrogen receptor-ß, and thyroid stimulating hormone receptors compared to NaF-intoxicated group. Additionally, NSO ameliorated tissue damage of the thyroid gland, ovary, and uterus induced by NaF. -Overall, the prophylactic group (NSO/NaF) performed better antioxidant and anti-inflammatory activities than the treated group almost in all examined tissues, which is reflected by the improvement in the structure of the thyroid, ovarian, and uterine tissues.

Understanding fenpropathrin-induced pulmonary toxicity: What apoptosis, inflammation, and pyreptosis reveal analyzing cross-links at the molecular, immunohistochemical, and immunofluorescent levels.

Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.

New insights into the anticancer effects of Polycladia crinita aqueous extract and its selenium nanoformulation against the solid Ehrlich carcinoma model in mice via VEGF, notch 1, NF-кB, cyclin D1, and caspase 3 signaling pathway.

Background: Phaeophyceae species are enticing interest among researchers working in the nanotechnology discipline, because of their diverse biological activities such as anti-inflammatory, antioxidant, anti-microbial, and anti-tumor. In the present study, the anti-cancer properties of Polycladia crinita extract and green synthesized Polycladia crinita selenium nanoparticles (PCSeNPs) against breast cancer cell line (MDA-MB-231) and solid Ehrlich carcinoma (SEC) were investigated. Methods: Gas chromatography-mass spectroscopy examinations of Polycladia crinita were determined and various analytical procedures, such as SEM, TEM, EDX, and XRD, were employed to characterize the biosynthesized PCSeNPs. In vitro, the anticancer activity of free Polycladia crinita and PCSeNPs was evaluated using the viability assay against MDA-MB-231, and also cell cycle analysis by flow cytometry was determined. Furthermore, to study the possible mechanisms behind the in vivo anti-tumor action, mice bearing SEC were randomly allocated into six equal groups (n = 6). Group 1: Tumor control group, group 2: free SeNPs, group 3: 25 mg/kg Polycladia crinita, group 4: 50 mg/kg Polycladia crinita, group 5: 25 mg/kg PCSeNPs, group 6: 50 mg/kg PCSeNPs. Results: Gas chromatography-mass spectroscopy examinations of Polycladia crinita extract exposed the presence of many bioactive compounds, such as 4-Octadecenoic acid-methyl ester, Tetradecanoic acid, and n-Hexadecenoic acid. These compounds together with other compounds found, might work in concert to encourage the development of anti-tumor activities. Polycladia crinita extract and PCSeNPs were shown to inhibit cancer cell viability and early cell cycle arrest. Concentrations of 50 mg/kg of PCSeNPs showed suppression of COX-2, NF-кB, VEGF, ki-67, Notch 1, and Bcl-2 protein levels. Otherwise, showed amplification of the caspase 3, BAX, and P53 protein levels. Moreover, gene expression of caspase 3, caspase 9, Notch 1, cyclin D1, NF-кB, IL-6, and VEGF was significantly more effective with PCSeNPs than similar doses of free extract. Conclusion: The PCSeNPs mediated their promising anti-cancerous action by enhancing apoptosis and mitigating inflammation, which manifested in promoting the total survival rate and the tumor volume decrease.

Exploring the link between pyrethroids exposure and dopaminergic degeneration through morphometric, immunofluorescence, and in-silico approaches: the therapeutic role of chitosan-encapsulated curcumin nanoparticles.

Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson's disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE's toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses. Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment.

Pulmonary damage induction upon Acrylic amide exposure via activating miRNA-223-3p and miRNA-325-3p inflammasome/pyroptosis and fibrosis signaling pathway: New mechanistic approaches of A green-synthesized extract.

Exposure to acrylic amide (AD) has garnered worldwide attention due to its potential adverse health effects, prompting calls from the World Health Organization for intensified research into associated risks. Despite this, the relationship between oral acrylic amide (acrylamide) (AD) exposure and pulmonary dysfunction remains poorly understood. Our study aimed to investigate the correlation between internal oral exposure to AD and the decline in lung function, while exploring potential mediating factors such as tissue inflammation, oxidative stress, pyroptosis, and apoptosis. Additionally, we aimed to evaluate the potential protective effect of zinc oxide nanoparticles green-synthesized moringa extract (ZNO-MONPs) (10 mg/kg b.wt) against ACR toxicity and conducted comprehensive miRNA expression profiling to uncover novel targets and mechanisms of AD toxicity (miRNA 223-3 P and miRNA 325-3 P). Furthermore, we employed computational techniques to predict the interactions between acrylic amide and/or MO-extract components and tissue proteins. Using a rat model, we exposed animals to oral acrylamide (20 mg/kg b.wt for 2 months). Our findings revealed that AD significantly downregulated the expression of miRNA 223-3 P and miRNA 325-3 P, targeting NLRP-3 & GSDMD, respectively, indicating the induction of pyroptosis in pulmonary tissue via an inflammasome activating pathway. Moreover, AD exposure resulted in lipid peroxidative damage and reduced levels of GPX, CAT, GSH, and GSSG. Notably, AD exposure upregulated apoptotic, pyroptotic, and inflammatory genes, accompanied by histopathological damage in lung tissue. Immunohistochemical and immunofluorescence techniques detected elevated levels of indicative harmful proteins including vimentin and 4HNE. Conversely, concurrent administration of ZNO-MONPs with AD significantly elevated the expression of miRNA 223-3 P and miRNA 325-3 P, protecting against oxidative stress, apoptosis, pyroptosis, inflammation, and fibrosis in rat lungs. In conclusion, our study highlights the efficacy of ZNO-MONPs NPs in protecting pulmonary tissue against the detrimental impacts of foodborne toxin AD.

Protective effect of Petroselinum crispum methanolic extract against acrylamide-induced reproductive toxicity in male rats through NF-ĸB, kinesin, steroidogenesis pathways.

This study examined the protective effects of a Petroselinum crispum (P. crispum) methanolic extract on reproductive dysfunction induced by acrylamide in male rats. A total of 40 rats were divided into four groups (n=10). The control group received distilled water, the acrylamide group received 10 mg/kg of acrylamide, the P. crispum group received 100 mg/kg of P. crispum extract, and the combined group was pretreated with P. crispum for two weeks before co-administration of P. crispum and acrylamide. All administrations were administered orally using a gastric tube for eight weeks. Acrylamide decreased testosterone levels but did not affect levels of FSH or LH. It also increased testicular levels of (MDA) malondialdehyde and reduced activity of (SOD) superoxide dismutase and impairment of sperm parameters. Furthermore, the administration of acrylamide resulted in an elevation of tumor necrosis factor-alpha (TNF-α) levels and a reduction in the levels of steroidogenic acute regulatory protein (STAR) and cytochrome P450scc (P450scc). Acrylamide negatively affected the histopathological outcomes, Johnsen's score, the diameter of seminiferous tubules, and the thickness of the germinal epithelium. It also upregulated the expression of NF-ĸB P65 and downregulated the expression of kinesin motor protein. In contrast, treatment with P. crispum extract restored the levels of antioxidant enzymes, improved sperm parameters, and normalized the gene expression of TNF-α, IL-10, IL-6, iNOS, NF-ĸB, STAR, CYP17A1, 17ß-HSD and P450scc. It also recovered testicular histological parameters and immunoexpression of NF-ĸB P65 and kinesin altered by acrylamide. P. crispum showed protective effects against acrylamide-induced reproductive toxicity by suppressing oxidative damage and inflammatory pathways.

Assessment of Anti-Alzheimer Pursuit of Jambolan Fruit Extract and/or Choline against AlCl3 Toxicity in Rats.

Jambolan fruit extract and choline were investigated for Aluminum tri chloride (AlCl3)-induced Alzheimer's disease in rats. Thirty-six male "Sprague Dawley" rats weighing (150 ± 10 g) were allocated into six groups; the first group was fed a baseline diet and served as a negative control. Alzheimer's disease (AD) was induced in Group 2 rats by oral administration of AlCl3 (17 mg/kg body weight) dissolved in distilled water (served as a positive control). Rats in Group 3 were orally supplemented concomitantly with both 500 mg/kg BW of an ethanolic extract of jambolan fruit once daily for 28 days and AlCl3 (17 mg/kg body weight). Group 4: Rivastigmine (RIVA) aqueous infusion (0.3 mg/kg BW/day) was given orally to rats as a reference drug concomitantly with oral supplementation of AlCl3 (17 mg/kg body weight) for 28 days. Group 5 rats were orally treated with choline (1.1 g/kg) concomitantly with oral supplementation of AlCl3 (17 mg/kg body weight). Group 6 was given 500 mg/kg of jambolan fruit ethanolic extract and 1.1 g/kg of choline orally to test for additive effects concurrently with oral supplementation of AlCl3 (17 mg/kg bw) for 28 days. Body weight gain, feed intake, feed efficiency ratio, and relative brain, liver, kidney, and spleen weight were calculated after the trial. Brain tissue assessment was analyzed for antioxidant/oxidant markers, biochemical analysis in blood serum, a phenolic compound in Jambolan fruits extracted by high-performance liquid chromatography (HPLC), and histopathology of the brain. The results showed that Jambolan fruit extract and choline chloride improved brain functions, histopathology, and antioxidant enzyme activity compared with the positive group. In conclusion, administering jambolan fruit extract and choline can lower the toxic impacts of aluminum chloride on the brain.

Ameliorative Effect of Thymoquinone and Thymoquinone Nanoparticles against Diazinon-Induced Hepatic Injury in Rats: A Possible Protection Mechanism.

The health benefits of thymoquinone (TQ) have been a significant focus of numerous studies. However, more research is needed to ascertain whether its nano-form can effectively treat or prevent chronic diseases. In this study, we investigated how thymoquinone and its nanoparticles can mitigate liver damage induced by diazinon in male Wistar rats and explored the intracellular mechanisms involved. Forty-two Wistar male rats (n = 42) were randomly allotted into seven groups. Group 1 served as the control. Group 2 (vehicle) consisted of rats that received corn oil via a gastric tube daily. In Group 3 (TQ), rats were given a daily oral administration of TQ (40 mg/kg bw). Group 4 (thymoquinone nanoparticles, NTQ) included rats that received NTQ (0.5 mg/kg bw) orally for 21 days. Group 5 (DZN) involved rats that were administered diazinon (DZN, 15 mg/kg bw) orally. In Group 6 (TQ + DZN), rats first received TQ orally, followed by DZN. Group 7 (NTQ + DZN) consisted of rats receiving NTQ orally, then DZN. After 21 days of treatment, the rats were euthanized. After oral administration of DZN, liver enzymes were significantly elevated (p < 0.05). Additionally, there were noticeable increases in oxidative injury markers, such as nitric oxide, malondialdehyde, redox oxygen radicals, and overall increases in hydrogen peroxide and liver protein carbonyl concentrations. This was accompanied by the upregulation of apoptotic markers (Bax, caspase9, caspase 3, bax/Bcl2 ratio), inflammatory cytokines (TNF-α, IL-6), and DNA damage. There was also a noteworthy decrease (p < 0.05) in the activities of antioxidant enzymes and anti-apoptotic markers. However, the oral administration of thymoquinone or its nanoparticle form mitigated these diazinon complications; our histopathological findings corroborated our biochemical and molecular observations. In conclusion, the significant antioxidant properties of thymoquinone, or its nanoparticle form, in tandem with the downregulation of apoptotic markers and inflammatory cytokines, provided a protective effect against hepatic dysfunction caused by diazinon.

Comparative Study on the Phytochemical Characterization and Biological Activities of Azolla caroliniana and Azolla filiculoides: In Vitro Study.

Azolla is a floating fern known for its various biological activities. Azolla caroliniana and Azolla filiculoides are multifunctional plants that exhibit biological activity in multiple ways, making them beneficial for various applications. This study aimed to compare the phytochemical composition and antimicrobial, antioxidant, anti-inflammatory, and cytotoxicity activities of two Azolla species, namely Azolla caroliniana and Azolla filiculoides. GC-MS analysis revealed distinct patterns of phytochemical composition in the two species. The methanol extracts of A. caroliniana and A. filiculoides exhibited moderate antimicrobial activity against Geotrichum candidum, Enterococcus faecalis, and Klebsiella pneumonia. Furthermore, both extracts demonstrated potential antioxidant activity, as evidenced by a dose-dependent increase in a ferric-reducing activity power (FRAP) assay. Additionally, the extracts showed promising anti-inflammatory activities, including inhibition of protein denaturation, heat-induced red blood cell (RBC) hemolysis, and nitric oxide (NO) production by macrophages. Moreover, the methanolic extracts of A. caroliniana displayed higher cytotoxicity against HepG2 cells than those of A. filiculoides in a dose-dependent manner. These findings suggest that the methanolic extracts of A. caroliniana and A. filiculoides contain distinct compounds and exhibit potential antioxidant, anti-inflammatory, and cytotoxic activities against HepG2 cells. In conclusion, our data indicate that the methanolic extracts of A. caroliniana and A. filiculoides have differential phytochemical compositions and possess potential antioxidant, anti-inflammatory, and HepG2 cytotoxic activities.

Mechanistic Assessment of Anise Seeds and Clove Buds against the Neurotoxicity Caused by Metronidazole in Rats: Possible Role of Antioxidants, Neurotransmitters, and Cytokines.

Long-term use of the nitroimidazole-derived antibiotic metronidazole has been associated with neuronal damage due to its ability to cross the blood-brain barrier. Polyphenol-rich plants, such as anise seeds and clove buds, are suggested to have neuroprotective effects. However, their intracellular protective pathway against metronidazole-induced neurotoxicity remains unexplored. This study aims to evaluate the potential neuroprotective benefits of anise seeds and clove buds and elucidate the proposed metronidazole-induced neurotoxicity mechanism. This study divided rats into six groups, each containing six rats. In Group I, the control group, rats were administered saline orally. Group II rats received 200 mg/kg of metronidazole orally. Group III rats received 250 mg/kg b.w. of anise seed extract and metronidazole. Group IV rats received 500 mg/kg b.w. of anise seed extract (administered orally) and metronidazole. Group V rats received 250 mg/kg b.w. of clove bud extract (administered orally) and metronidazole. Group VI rats were administered 500 mg/kg b.w. of clove bud extract and metronidazole daily for 30 consecutive days. The study evaluated the phenolic compounds of anise seeds and clove buds. Moreover, it assessed the inflammatory and antioxidant indicators and neurotransmitter activity in brain tissues. A histological examination of the brain tissues was conducted to identify neuronal degeneration, brain antioxidants, and apoptotic mRNA expression. The study found that metronidazole treatment significantly altered antioxidant levels, inflammatory mediators, and structural changes in brain tissue. Metronidazole also induced apoptosis in brain tissue and escalated the levels of inflammatory cytokines. Oral administration of metronidazole resulted in a decrease in GABA, dopamine, and serotonin and an increase in ACHE in brain tissue. Conversely, oral administration of anise and clove extracts mitigated the harmful effects of metronidazole. The neurotoxic effects of metronidazole appear to stem from its ability to reduce antioxidants in brain tissue and increase nitric oxide production and apoptosis. The study concludes that neuronal damage caused by metronidazole is significantly mitigated by treatment with anise and clove extracts.