The emerging role of α7nAChRs/caspase-3/Nrf-2 signaling pathway in citicoline improved autistic behavior induced by thimerosal in mice.

AIMS: Autism spectrum disorder (ASD) is a global concern,affecting around 75 million individuals.Various factors contribute to ASD,including mercury-containing preservatives like thimerosal (Thim) found in some vaccines.This study explored whether citicoline could be a therapeutic option for Thim-induced neuronal damage in a mouse model of ASD.Additionally,the study investigated the effects of citicoline on the α7nAChRs/Akt/Nrf2/caspase-3 pathway,which may be involved in the development of ASD. MATERIALS AND METHODS: The study separated newborn mice into four groups.The control group received saline injections,while the Thim group received intramuscular injections of 3000 µg Hg/kg Thim on days 7,9,11,and 15 after birth.The two citicoline groups were administered Thim followed by intraperitoneal injections of 250 mg/kg or 500 mg/kg citicoline for three weeks.Afterward,various parameters were assessed, including growth,behavior,brain histopathology,oxidative stress,apoptotic,and inflammatory markers. KEY FINDINGS: Untreated Thim-exposed mice exhibited significant brain damage,which was substantially alleviated by citicoline treatment.This beneficial effect was associated with increased expressions and concentrations of brain α7nAChRs and Akt, increased brain content of Nrf2, and the hippocampus contents of acetylcholine. Citicoline treatment decreased the brain levels of oxidative stress markers (MDA and NO),the apoptotic marker caspase-3,and pro-inflammatory markers (NF-κB,TNF-α,and IL-1ß). The drug also increased the brain GPx activity. SIGNIFICANCE: Based on the results of this study,the α7nAChRs pathway appears to be essential for the therapeutic effectiveness of citicoline in treating Thim-induced ASD in mice.

Morphine aggravates inflammatory, behavioral, and hippocampal structural deficits in septic rats.

Although pain and sepsis are comorbidities of intensive care units, reported data on whether pain control by opioid analgesics could alter inflammatory and end-organ damage caused by sepsis remain inconclusive. Here, we tested the hypothesis that morphine, the gold standard narcotic analgesic, modifies behavioral and hippocampal structural defects induced by sepsis in male rats. Sepsis was induced with cecal ligation and puncture (CLP) and behavioral studies were undertaken 24 h later in septic and/or morphine-treated animals. The induction of sepsis or exposure to morphine (7 mg/kg) elicited similar: (i) falls in systolic blood pressure, (ii) alterations in spatial memory and learning tested by the Morris water maze, and (iii) depression of exploratory behavior measured by the new object recognition test. These hemodynamic and cognitive defects were significantly exaggerated in septic rats treated with morphine compared with individual interventions. Similar patterns of amplified inflammatory (IL-1ß) and histopathological signs of hippocampal damage were noted in morphine-treated septic rats. Additionally, the presence of intact opioid receptors is mandatory for the induction of behavioral and hemodynamic effects of morphine because no such effects were observed when the receptors were blocked by naloxone. That said, our findings suggest that morphine provokes sepsis manifestations of inflammation and interrelated hemodynamic, behavioral, and hippocampal deficits.

Panax ginseng ameliorates hepatorenal oxidative alterations induced by commercially used cypermethrin in male rats: experimental and molecular docking approaches.

Cypermethrin (CYP) is a synthetic pyrethroid utilized as an insecticide in agriculture and various pest eradication programs. However, it induces numerous health hazards for animals and humans. Therefore, the current study used Panax ginseng root extract (ginseng) to reduce the hepatorenal damage caused by commercially used CYP. Thirty-two male Wistar albino rats were distributed into control, ginseng (300 mg/kg B.W/day), CYP (4.67 mg/kg B.W.), and Ginseng+CYP (rats received both CYP and ginseng). All treatments were administered orally for 30 consecutive days. Cypermethrin induced harmful effects on hepatic and renal tissues through a substantial decline in body weight in addition to a considerable increase in liver enzymes, functional renal markers, and cholesterol. Also, CYP significantly decreased acetylcholinesterase (AChE) activity and increased pro-inflammatory cytokines (interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α)). Moreover, a marked increase in malondialdehyde level with a significant drop in reduced glutathione level and total superoxide dismutase (T-SOD) and catalase (CAT) activities was reported in the CYP group in kidney and liver tissues. Additionally, CYP exhibited affinities to bind and inhibit AChE and antioxidant enzymes (T-SOD and CAT) in rats following the molecular docking modeling. The apparent hepatorenal oxidative damage was linked with obvious impairments in the liver and kidney histoarchitecture, immunohistochemical staining of B cell lymphoma-2 (Bcl-2), and caspase-3 proteins. Ginseng reduced CYP's oxidative alterations by repairing the metabolic functional markers, improving antioxidant status, reducing the inflammatory response, and enhancing the molecular docking evaluation. It also ameliorated the intensity of the histopathological alterations and improved the immunohistochemical staining of Bcl-2 and caspase-3 proteins in the liver and kidney tissues. Finally, concomitant oral administration of ginseng mitigated CYP-prompted hepatorenal damage through its antioxidant, anti-inflammatory, and anti-apoptotic potentials.

Maternal and paternal obesity differentially reprogram the ovarian mitochondrial biogenesis of F1 female rats.

Obesity has harmful consequences on reproductive outcomes and the rapid increase in obesity is assumed to be influenced by epigenetics and trans-generation effects. Our study aimed to explore the effect of maternal and/or paternal obesity on the ovarian tissues of the first-generation female offspring in rats. The study was conducted on 40 adult Wistar albino rats (20 males and 20 females). Obesity was induced by feeding them an obesogenic diet for 3 months. The pregnancy was induced in the females by mating with males in four combinations: healthy mother with healthy father (control parents, CP), healthy mother with obese fathers (OF), obese mothers with healthy father (OM), and obese mother with obese father (obese parents, OP). After delivery, the female offspring at two months were sacrificed, and the blood and ovarian tissues were collected to assess the studied parameters. Our result showed differential impacts of maternal and paternal obesity on the ovarian health of the female offspring. The female offspring of obese OM or OP showed early signs of obesity. These metabolic abnormalities were associated with signs of ovarian lesions, impaired folliculogenesis, and decreased oocyte quality and also showed significant alterations in mitochondrial biogenesis, redox status, inflammation, and microRNAs expression (miR-149 and miR-494). In conclusion, altered ovarian expression of microRNAs and associated impaired mitochondrial biogenesis pathways may be the root causes for the observed intergeneration transmission of the obesogenic phenotype.

Mitochondrial modulation of amplified preconditioning influences of remote ischemia plus erythropoietin against skeletal muscle ischemia/reperfusion injury in rats.

AIMS: Skeletal muscle ischemia and reperfusion (S-I/R) injury is relieved by interventions like remote ischemic preconditioning (RIPC). Here, we tested the hypothesis that simultaneous exposure to a minimal dose of erythropoietin (EPO) boosts the protection conferred by RIPC against S-I/R injury and concomitant mitochondrial oxidative and apoptotic defects. MAIN METHODS: S-I/R injury was induced in rats by 3-h right hindlimb ischemia followed by 3-h of reperfusion, whereas RIPC involved 3 brief consecutive I/R cycles of the contralateral hindlimb. KEY FINDINGS: S-I/R injury caused (i) rises in serum lactate dehydrogenase and creatine kinase and falls in serum pyruvate, (ii) structural deformities like sarcoplasm vacuolations, segmental necrosis, and inflammatory cells infiltration, and (iii) decreased amplitude and increased duration of electromyography action potentials. These defects were partially ameliorated by RIPC and dose-dependently by EPO (500 or 5000 IU/kg). Further, greater repairs of S-I/R-evoked damages were seen after prior exposure to the combined RIPC/EPO-500 intervention. The latter also caused more effective (i) preservation of mitochondrial number (confocal microscopy assessed Mitotracker red staining) and function (citrate synthase activity), (ii) suppression of mitochondrial DNA damage and indices of oxidative stress and apoptosis (succinate dehydrogenase, myeloperoxidase, cardiolipin, and cytochrome c), (iii) preventing calcium and nitric oxide metabolites (NOx) accumulation and glycogen consumption, and (iv) upregulating EPO receptors (EPO-R) gene expression. SIGNIFICANCE: dual RIPC/EPO conditioning exceptionally mends structural, functional, and neuronal deficits caused by I/R injury and interrelated mitochondrial oxidative and apoptotic damage. Clinically, the utilization of relatively low EPO doses could minimize the hormone-related adverse effects.

Integrated serum pharmacochemistry and network pharmacology analyses reveal the bioactive metabolites and potential functional mechanism of ground cherry (Physalis pruinosa L.) in treatment of type 2 diabetes mellitus in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Different Physalis plants have been widely employed in traditional medicine for management of diabetes mellitus. Previous studies with respect to the in vivo antidiabetic activity of Physalis plants illustrated that they improved glucose and lipid metabolism in streptozotocin (STZ) -induced diabetic rats yet the mechanism of action of bioactive constituents of the different organs of Physalis plants on diabetes remains obscure. AIM OF STUDY: Our objective is to study the effects of the different organs of ground cherry (P. pruinosa) on diabetes in rat models and elucidate their mechanism of actions through serum pharmacochemistry combined to network pharmacology analyses and in-vivo testing. MATERIALS AND METHODS: Characterization of the constituents in the drug-dosed serum samples relative to the blank serum after treatment with different extracts was performed by UPLC -MS/MS technique. The absorbed metabolites where then subjected to network pharmacology analysis to construct an interaction network linking "compound-target-pathway". In vivo verification was implemented to determine a hypothesized mechanism of action on a STZ and high fat diet induced type II diabetes mellitus (T2DM) model based on functional and enrichment analyses of the Kyoto Encyclopedia of Genes and Genome and Gene Ontology. RESULTS: Identification of a total of 73 compounds (22 prototypes and 51 metabolites) derived from P. pruinosa extracts was achieved through comparison of the serum samples collected from diabetic control group and extracts treated groups. The identified compounds were found to belong to different classes according to their structural type including withanolides, physalins and flavonoids. The absorbed compounds in the analyzed serum samples were considered as the potential bioactive components. The component-target network was found to have 23 nodes with 17 target genes including MAPK8, CYP1A1 and CYP1B1. Quercetin and withaferin A were found to possess the highest combined score in the C-T network. Integrated serum pharmacochemistry and network pharmacology analyses revealed the enrichment of leaves extract with the active constituents, which can be utilized in T2DM treatment. In the top KEGG pathways, lipid and atherosclerosis metabolic pathways in addition to T2DM pathways were found to be highly prioritized. The diabetic rats, which received leaves extract exhibited a substantial increment in GLUT2, INSR, IRS-1, PI3K-p85 and AKT-ser473 proteins by 105%, 142%, 109%, 81% and 73%, respectively relative to the untreated diabetic group. The immunoblotting performed for MAPK and ERK1/2 part of the inflammatory pathway studied in STZ induced diabetic rats revealed that leaves, calyces and stems extracts resulted in a substantial diminish in p38-MAPK, ERK 1/2, NF-κB, and TNF-α. Histopathological examination revealed that the hepatic histoarchitecture was substantially improved in the leaves, stems, and clayces-treated rats in comparison with untreated diabetic rats. Further, pancreatic injuries, which induced by STZ were dramatically altered by the treatment with P. pruinosa leaves, calyces and stems extracts. ß-cells in diabetic rats received leaves extract disclosed moderate insulin immunostaining with a notable increase in the mean insulin area%. CONCLUSIONS: The study in hand offers a comprehensive study to clarify the bioactive metabolites of the different organs of P. pruinosa. The basic pharmacological effects and underlying mechanism of actions in the management of STZ and high fat diet induced T2DM were specifically covered in this paper.

Gestational NSAIDs distinctly reprogram cardiac injury in preeclamptic rats: Roles of cyclooxygenase, apoptotic and autophagic trails.

AIMS: Considering the role of cyclooxygenases (COX) in placental programming induced by preeclampsia (PE), we investigated whether gestational exposure to nonsteroidal antiinflammatory drugs (NSAIDs) with different COX-1/2 selectivity would variably modulate pre- and postnatal (weaning time, i.e. 3 weeks after delivery) cardiovascular manifestations of PE. MATERIALS AND METHODS: PE was induced by oral administration of Nω-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day for 7 days) to pregnant rats starting from day 14 of gestation. Rats were treated simultaneously with celecoxib (10 mg/kg/day), diclofenac (0.5 mg/kg/day), or naproxen (1 mg/kg/day). KEY FINDINGS: Tail-cuff measurements revealed a higher systolic blood pressure (SBP) in PE mothers at gestational day 20 (GD20). More exaggerated rises in prenatal SBP were noted in PE rats treated with celecoxib but not diclofenac or naproxen. Higher levels of serum creatine and kinase MB (CK-MB), a biomarker of cardiac damage, were demonstrated in weaning PE rats and this effect was suppressed by naproxen only. Additionally, naproxen was the most effective among all 3 NSAIDs in diminishing the PE-induced surges in (i) cardiomyocyte cross-sectional area, (ii) cardiac COX-1/COX-2 activities, (iii) arachidonate metabolites (PGE2, PGF2α, and TXA2), (iv) caspase-3 and beclin-1 expressions. By contrast, the PE-related increments in cardiac expression of antiangiogenic (sFlt-1, and endoglin-1) and inflammatory (nuclear factor kappa B, NF-κB) factors were indiscriminately reduced by all NSAIDs. SIGNIFICANCE: Compared with celecoxib or diclofenac, naproxen appears to be the most advantageous in minimizing cardiac damage in weaning PE rats due to its synchronized downregulatory effects on cyclooxygenase, apoptotic, and autophagic pathways.

Potential cardioprotective effect of octreotide via NOXs mitigation, mitochondrial biogenesis and MAPK/Erk1/2/STAT3/NF-kß pathway attenuation in isoproterenol-induced myocardial infarction in rats.

Myocardial infarction (MI) is a global health care problem, which instigates irreversible cardiac tissue damage and sudden death, necessitating new prevention and management strategies. Hence, the cardioprotective effect of octreotide in MI was scrutinized by tackling the possible underlying trajectories involved. Isoproterenol (ISO)-induced acute MI model was adopted using ISO (85 mg/kg/day, S.C.) for 2 days. Rats in octreotide groups were pretreated with 20 or 40 µg/kg/day S.C. for 8 days and ISO was given on the 7th and 8th days. Octreotide showed a restoration of ECG changes, cardiac hemodynamics abnormalities, serum cardiac markers elevation (creatine kinase MB, troponin I, lactate dehydrogenase, and aspartate aminotransferase), and cardiac histoarchitecture abnormalities. In addition, octreotide pretreatment showed a significant increase in the cardiac and serum level of the diagnostic microRNA-133a. Octreotide attenuates oxidative stress indices (MDA, GSH, SOD, TAC, and HIF-1α), besides a better adjustment of NOX-1/-2/-4 expression and protein levels. Mitochondrial morphology and mtDNA copy number were preserved following the pre-treatment of Octreotide. The inflammatory pathway p38 MAPK/Erk-1/-2/p-STAT3/NF-κB pathway and the proinflammatory cytokines (TNF- α, IL-6, and IL- 1ß) were attenuated. The proapoptotic markers (cyt c, caspase-3/-9, and Bax) were also attenuated and the antiapoptotic Bcl2 marker was increased by the preadministration of octreotide. In almost all parameters, Octreotide 40 µg/kg/day was more prominent than its lower dose. Octreotide possesses dose-dependent cardioprotective properties via its antioxidant, anti-inflammatory, and anti-apoptotic capabilities.

Quercetin Abrogates Oxidative Neurotoxicity Induced by Silver Nanoparticles in Wistar Rats.

This study aimed to investigate the oxidative neurotoxicity induced by silver nanoparticles (AgNPs) and assess the neuroprotective effects of quercetin against this toxicity. Forty adult male rats were divided into four equal groups: control, AgNPs (50 mg/kg intraperitoneally), quercetin (50 mg/kg orally), and quercetin + AgNPs. After 30 days, blood and brain tissue samples were collected for further studies. AgNP exposure increased lipid peroxidation and decreased glutathione peroxidase, catalase, and superoxide dismutase activities in brain tissue. AgNPs decreased serum acetylcholine esterase activity and γ-aminobutyric acid concentrations. AgNPs upregulated tumor necrosis factor-α, interleukin-1ß, and Bax transcript levels. AgNPs reduced the transcripts of claudin-5, brain-derived neurotrophic factor, paraoxonase, nuclear factor-erythroid factor 2 (Nrf2), and Bcl-2. Histopathologically, AgNPs caused various degenerative changes and neuronal necrosis associated with glial cell reactions. AgNPs increased the immunohistochemical staining of glial fibrillary acidic protein (GFAP) in the cerebrum and cerebellum. Oral treatment with quercetin efficiently counteracted the opposing effects of AgNPs on brain tissue via modulation of tight junction proteins, Nrf2, and paraoxonase, and its positive mechanism in modulating pro-inflammatory cytokines and the downregulation of GFAP expression, and the apoptotic pathway. AgNPs also altered the severity of histopathological lesions and modulated GFAP immunostaining in the examined tissue.

Studying ferroptosis and pyroptosis as new cell death mechanisms induced by ionizing radiation in Ehrlich solid tumor-bearing mice.

OBJECTIVE: Our objective was to explore the effect of different fractionation schedule on ferroptosis and pyroptosis biomarkers as new cell death mechanisms induced by IR. MATERIALS AND METHODS: This study included 40 tumor bearing mice divided into: Group I: Includes 8 untreated tumor-bearing mice. Group II: Includes 8 tumor bearing mice exposed to single dose 6 Gy of IR. Group III: Includes 8 tumor bearing mice exposed to 12 Gy in 2 fractions (2 × 6 Gy) of IR. Group IV: Includes 8 tumor bearing mice exposed to 12 Gy in 3 fractions (3 × 4 Gy) of IR. Group V: Includes 8 tumor bearing mice exposed to 8 Gy in 4 fractions (4 × 2 Gy) of IR. IL-1ß, IL-18, and GSDMD-CT levels were assessed by ELISA. PTGS2 and ACSL4 expression were assessed by RT-PCR. RESULTS: (2 × 6 Gy) group showed the highest ACSL4 expression followed by (3 × 4 Gy), then (4 × 2 Gy) and finally 6 Gy. (2 × 6 Gy) group resulted in the highest PTGS2 expression followed by (3 × 4 Gy), then 6 Gy, and finally (4 × 2 Gy). MDA significantly increased at (2 × 6 Gy), (3 × 4 Gy), and 6 Gy groups and insignificantly increased at (4 × 2 Gy) group. Iron significantly increased at (2 × 6 Gy), (3 × 4 Gy), and (4 × 2 Gy) groups and insignificantly at 6 Gy. Glutathione was significantly decreased at (2 × 6 Gy), (3 × 4 Gy), and (4 × 2 Gy) groups and insignificantly at 6 Gy. GSDMD-CT, IL-1ß, and IL-18 levels significantly reduced in tumor tissues after exposure to IR at all doses. CONCLUSION: High dose per fraction regimens induce the expression of ferroptosis markers more than low dose per fraction regimen and single dose of IR. IR at all doses induces pyroptotic cell death.

Date Palm Pollen Extract Avert Doxorubicin-Induced Cardiomyopathy Fibrosis and Associated Oxidative/Nitrosative Stress, Inflammatory Cascade, and Apoptosis-Targeting Bax/Bcl-2 and Caspase-3 Signaling Pathways.

Doxorubicin (DOX) has a potent antineoplastic efficacy and is considered a cornerstone of chemotherapy. However, it causes several dose-dependent cardiotoxic results, which has substantially restricted its clinical application. This study was intended to explore the potential ameliorative effect of date palm pollen ethanolic extract (DPPE) against DOX-induced cardiotoxicity and the mechanisms underlying it. Forty male Wistar albino rats were equally allocated into Control (CTR), DPPE (500 mg/kg bw for 4 weeks), DOX (2.5 mg/kg bw, intraperitoneally six times over 2 weeks), and DPPE + DOX-treated groups. Pre-coadministration of DPPE with DOX partially ameliorated DOX-induced cardiotoxicity as DPPE improved DOX-induced body and heart weight changes and mitigated the elevated cardiac injury markers activities of serum aminotransferases, lactate dehydrogenase, creatine kinase, and creatine kinase-cardiac type isoenzyme. Additionally, the concentration of serum cardiac troponin I (cTnI), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-pro BNP), and cytosolic calcium (Ca+2) were amplified. DPPE also alleviated nitrosative status (nitric oxide) in DOX-treated animals, lipid peroxidation and antioxidant molecules as glutathione content, and glutathione peroxidase, catalase, and superoxide dismutase activities and inflammatory markers levels; NF-κB p65, TNF-α, IL-1ß, and IL-6. As well, it ameliorated the severity of histopathological lesions, histomorphometric alteration and improved the immune-staining of the pro-fibrotic (TGF-ß1), pro-apoptotic (caspase-3 and Bax), and anti-apoptotic (Bcl-2) proteins in cardiac tissues. Collectively, pre-coadministration of DPPE partially mitigated DOX-induced cardiac injuries via its antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic potential.

Ameliorative effects of astaxanthin on brain tissues of alzheimer's disease-like model: cross talk between neuronal-specific microRNA-124 and related pathways.

Alzheimer's disease (AD) is a chronic, progressive, multifactorial, and the most common neurodegenerative disease which causes dementia and mental deterioration in the elderly. The available treatments for AD are not disease-modifying drugs and only provide symptomatic relief. Astaxanthin (ATX), a second-generation antioxidant, is a dark red carotenoid and exhibits the highest antioxidant capacity, anti-inflammatory, neuroprotective, and antiapoptotic effects. In this study, we investigated the therapeutic effect of different doses of ATX on the cerebral cortex and hippocampus of AD-like rats. The AD-like model was induced in rats using hydrated aluminum chloride (AlCl3.6H2O) solution that was given orally at a dose of 75 mg/kg daily for 6 weeks. Morris water maze (MWM) behavioral test was performed to confirm the cognitive dysfunction then AD-like rats were orally treated with different doses of ATX (5, 10, and 15 mg/kg) dissolved in dimethyl sulfoxide (DMSO) for six weeks. The results indicated that ATX significantly and dose-dependently improved the performance of AD-like rats treated with ATX during MWM and suppress the accumulation of amyloid ß1-42 and malondialdehyde. Also, significantly inhibit acetylcholinesterase and monoamine oxidase activities and the expression of ß-site amyloid precursor protein cleaving enzyme 1 (BACE 1). ATX also significantly elevated the content of acetylcholine, serotonin, and nuclear factor erythroid-2-related factor 2 (Nrf2) and miRNA-124 expression. The effect of ATX treatment was confirmed by histopathological observations using H&E stain and morphometric tissue analysis. From this study, we concluded that ATX may be a promising therapeutic agent for AD through targeting different pathogenic pathways.

Date palm fruit extract ameliorated pancreatic apoptosis, endocrine dysfunction and regulatory inflammatory cytokines in Streptozotocin-induced diabetes in rats.

The current work studied the mechanism(s) and ability by which date palm (Phoenix dactylifera L.) fruit extract (DPE) inspired a glucose-lowering impact in rats suffering from diabetes. Forty-eight albino rats were divided into six various experimental treatments after induction of diabetes by intraperitoneal infusion of streptozotocin (45 mg/kg bwt) as follows: normal control, DPE, diabetic control, diabetic glibenclamide (GLI), diabetic DPE, and diabetic GLI plus DPE-treated groups. In animals euthanized after 8 weeks, blood and pancreatic tissue samples were assembled to assess different biochemical and histopathological changes. The expressions of insulin, B cell lymphoma-2 (Bcl-2), and cysteine aspartate-specific protease-3 (caspase-3) in islet ß cells were also evaluated using immunohistochemical assessment. Diabetic rats exhibited hyperglycemia; increment of pancreatic malondialdehyde (lipid peroxidation biomarker), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß); and decrement of plasma insulin and pancreatic antioxidants: glutathione, superoxide dismutase, and catalase values. Also, the pancreatic islets exhibited histopathological and morphometric alternations associated with weak positive insulin and Bcl-2 immunoreactivity and strong positive caspase-3 immunoreactivity. DPE and/or GLI, an anti-diabetic drug, improved the pancreatic histoarchitecture and improved ß cell function and structure, which increased insulin levels and improved the insulin, Bcl-2, and caspase-3 immunoreactivity in diabetic rats. Nevertheless, the combined DPE and GLI therapy revealed a significant recovery and restoration of ß cells' structure and function. The date palm fruit has anti-apoptotic, anti-inflammatory, and antioxidant activities and hypoglycemic effects, which in turn play a pivotal role in avoiding the progression of diabetes mellitus. Moreover, it could potentiate the glucose-lowering activity of anti-diabetic drugs.

Biomonitoring of Heavy Metal Pollution Using Acanthocephalans Parasite in Ecosystem: An Updated Overview.

As a result of the global industrial revolution, contamination of the ecosystem by heavy metals has given rise to one of the most important ecological and organismic problems, particularly human, early developmental stages of fish and animal life. The bioaccumulation of heavy metals in fish tissues can be influenced by several factors, including metal concentration, exposure time, method of metal ingestion and environmental conditions, such as water temperature. Upon recognizing the danger of contamination from heavy metals and the effects on the ecosystem that support life on earth, new ways of monitoring and controlling this pollution, besides the practical ones, had to be found. Diverse living organisms, such as insects, fish, planktons, livestock and bacteria can be used as bioindicators for monitoring the health of the natural ecosystem of the environment. Parasites have attracted intense interest from parasitic ecologists, because of the variety of different ways in which they respond to human activity contamination as prospective indices of environmental quality. Previous studies showed that fish intestinal helminths might consider potential bioindicators for heavy metal contamination in aquatic creatures. In particular, cestodes and acanthocephalans have an increased capacity to accumulate heavy metals, where, for example, metal concentrations in acanthocephalans were several thousand times higher than in host tissues. On the other hand, parasitic infestation in fish could induce significant damage to the physiologic and biochemical processes inside the fish body. It may encourage serious impairment to the physiologic and general health status of fish. Thus, this review aimed to highlight the role of heavy metal accumulation, fish histopathological signs and parasitic infestation in monitoring the ecosystem pollutions and their relationship with each other.

Modulatory role of dietary Thymus vulgaris essential oil and Bacillus subtilis against thiamethoxam-induced hepatorenal damage, oxidative stress, and immunotoxicity in African catfish (Clarias garipenus).

Thiamethoxam (TMX) is a widely used neonicotinoid insecticide for its effective potential for controlling insects from the agricultural field, which might induce toxicity to the aquatic biota. In this study, the role of the probiotic Bacillus subtilis (BS) and a phytogenic oil extract of Thymus vulgaris essential oil (TVEO) in the modulation of thiamethoxam (TMX)-induced hepatorenal damage, oxidative stress, and immunotoxicity in African catfish (Clarias garipenus) has been evaluated. Fish were subjected to TMX (5 mg L-1) and fed with a diet either supplemented with BS (1000 ppm) or TVEO (500 ppm). The experiment lasted for 1 month. By the end of the experiment, blood was sampled for biochemical analysis and fish organs and tissues were collected for histopathological and immunohistochemical examinations. Results showed a substantial increase of serum markers of hepatorenal damage such as the activities of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) and levels of blood urea nitrogen (BUN) and creatinine with an obvious decrease of serum protein levels in the TMX-intoxicated group. Also, there was a considerable increase in malondialdehyde (MDA) levels and glutathione-S-transferase (GST) activity. TMX remarkably suppressed serum lysozyme activity, respiratory burst activity, and phagocytosis with a conspicuous elevation of the levels of interleukins (interleukin-1 beta (IL-1ß) and interleukin-6 IL-6). The histopathological findings showed that TMX induced degenerative changes and necrosis in the gills, liver, head kidneys, and spleen of the intoxicated fish. Significant alterations of frequency, size, and area percentage of melanomacrophage centers (MMCs), decreased splenocyte proliferation, and increased number of caspase-3 immunopositive cells were also observed. Contrariwise, the concurrent supplementation of either BS or TVEO in the diets of catfish partially mitigated both the histopathological and histomorphometric lesions of the examined tissues. Correspondingly, they improved the counts of proliferating cell nuclear antigen (PCNA) and caspase-3 immunopositive splenocytes. In conclusion, the co-administration of either BS or TVEO in catfish diets partially diminished the toxic impacts of TMX. Nonetheless, the inclusion of TVEO in the diets of catfish elicited better protection than BS against TMX-induced toxicity in response to its potential anti-inflammatory, antioxidant, anti-apoptotic, and immune-stimulant effects.

Apoptosis and astrogliosis perturbations and expression of regulatory inflammatory factors and neurotransmitters in acrylamide-induced neurotoxicity under ω3 fatty acids protection in rats.

This study was aimed to investigate the potential ameliorative effects of omega-3 (ω3) fatty acids against acrylamide (ACR)-induced neurotoxicity. Thirty-two adult male Sprague Dawley rats were randomly assigned into four groups (n = 8) as follows: control, ω3 fatty acids (1000 mg/kg bwt/day orally), ACR-treated (50 mg/kg bwt/day IP) and ACR plus ω3 fatty acids group. Treatments were performed every other day for 21 consecutive days. ACR induced abnormal gait and elevated serum levels of proinflammatory cytokines (IL-6 and TNF-α), brain and spinal cord MDA levels and decreased brain and spinal cord GSH levels. Moreover, it reduced neurotransmitters (acetylcholine, GABA, serotonin and noradrenaline levels) and increased AChE activity in brain tissues. Histopathologically, ACR caused various degenerative changes, necrosis and glial cell activation in the cerebrum, cerebellum, hippocampus, spinal cord and sciatic nerve. Likewise, the histomorphometric analysis was constant with ACR-induced neurotoxicity. The ACR induced axonal atrophy and myelin disruption and decreased g-ratio of the sciatic nerve. Immunohistochemically, strong positive expressions of apoptotic marker caspase-3 and astroglial GFAP in the examined tissues were detected. Contrariwise, concurrent administration of ω3 fatty acids partially attenuated ACR impacts, as it improved the gait performance, reduced oxidative stress and pro-inflammatory cytokines, and modulate the levels of the neurotransmitters. It also ameliorated the intensity of ACR-induced histopathological and histomorphometric alterations within the examined nervous tissues. It could be concluded that ω3 fatty acids have antioxidant, anti-inflammatory and anti-apoptotic potentials against ACR neurotoxicity via suppression of oxidative stress, lipid peroxidation and pro-inflammatory cytokines, and inhibition of AChE activity and downregulation of caspase-3 and GFAP expressions in the nervous tissues.

Partial ameliorative effect of Moringa leaf ethanolic extract on the reproductive toxicity and the expression of steroidogenic genes induced by subchronic cadmium in male rats.

The impact of Moringa oleifera leaf ethanol extract (MOLEE) was assessed on the expression of the steroidogenic genes (steroidogenic acute regulatory protein (StAR) and cytochrome P450c17 subfamily a (CYP17a) and luteinizing hormone receptor (LHR) gene) as well as on the cadmium chloride (CdCl2)-induced reproductive toxicity for 56 days in male rats. Four groups were used: control, Moringa-treated (MOLEE), CdCl2-treated, and CdCl2 + MOLEE groups. The reproductive toxicity of CdCl2 was confirmed; it caused a significant decrease in the accessory sex organ weights, testosterone level, testicular GST level, elevated MDA level (lipid peroxidation indicator), and histopathological alterations in seminiferous tubules, prostate, seminal vesicles, and epididymis as well as sperm characteristics. It also induced downregulation in the expression of StAR and CYP17a genes without change in the expression LHR gene. Eleven active compounds were detected in the GC-MS analysis of MOLEE; six of them have antioxidant properties, and five new compounds presented variable activities. MOLEE alone induced a stimulatory effect on the expression of steroidogenic and LHR genes. It restored the weight of reproductive organs to the control level; however, the recovery in sperm count, motility, abnormalities, percentage of alive sperm, testosterone, and MDA level are still comparable with the control level. Similar findings were also reported at the histological structure of the testes, epididymis, and accessory sex glands. Complete recovery of the GST enzyme activity was observed. Additionally, a restoration in the expression level of the steroidogenic genes was also reported. Our results indicated that the concurrent administration of MOLEE with CdCl2 can partially mitigate its harmful effects on male fertility.

L-α-Phosphatidylcholine attenuates mercury-induced hepato-renal damage through suppressing oxidative stress and inflammation.

The potential ameliorative effects of L-α-phosphatidylcholine (PC) against mercuric chloride (HgCl2)-induced hematological and hepato-renal damage were investigated. Rats were randomly allocated into four groups (n = 12): control, PC (100 mg/kg bwt, intragastrically every other day for 30 consecutive days), HgCl2 (5 mg/kg bwt, intragastrically daily), and PC plus HgCl2. Hematological and hepato-renal dysfunctions were evaluated biochemically and histopathologically. Hepatic and renal oxidative/antioxidative indices were evaluated. The expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) was also detected by ELISA. HgCl2 significantly increased serum aminotransferases (ALT, AST), urea, and creatinine levels that are indicative of hepato-renal damage. HgCl2 also induced a significant accumulation of malondialdehyde (+ 195%) with depletion of glutathione (- 43%) levels in the liver and renal tissues. The apparent hepato-renal oxidative damage was associated with obvious organ dysfunction that was confirmed by impairments in the liver and kidney histoarchitecture. Furthermore, HgCl2 significantly attenuated the expression of proinflammatory cytokines named tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Conversely, PC treatment attenuated these effects, which improved the hematological and serum biochemical alternations, reduced the oxidative stress and proinflammatory cytokine levels, and ameliorated the intensity of the histopathological alterations in livers and kidneys of HgCl2-treated rats. It could be concluded that PC displayed potential anti-inflammatory and antioxidant activities against HgCl2-induced hepato-renal damage via suppression of proinflammatory cytokines and declining oxidative stress.