Therapeutic effects of intermittent fasting on high-fat, high-fructose diet; involvement of jejunal aquaporin 1, 3, and 7.

Background: Aquaporins (AQPs) are transmembrane channel proteins. Aquaporin 1 (AQP1), Aquaporin 3 (AQP3), and Aquaporin 7 (AQP7) are expressed in the jejunum. The purpose of this study was to ascertain how a high-fat high-fructose diet (HFFD) and intermittent fasting (IF) affect AQP1, AQP3, and AQP7 expression in the rat jejunum. Methods: Sixteen adult male rats were divided into control rats (n = 4) fed on a basal diet and water ad libitum for 12 weeks; IF control rats (n = 4) followed the IF protocol, HFFD-fed rats (n = 8) fed HFFD for eight weeks, and rats were randomized into two groups: HFFD only or HFFD and IF protocol from the beginning of the 9th week until the end of the experiment. The lipid profile values were assessed after 12 weeks. Jejunal oxidative markers (malondialdehyde and reduced glutathione) and AQP1, AQP3, and AQP7 mRNA expression were measured. Jejunal sections were used for morphometric analysis of villus length and crypt depth. Immunohistochemical evaluation of AQP1, AQP3, and AQP7 expression was also performed. Results: IF ameliorates HFFD-induced lipid profile, oxidative stress, and jejunal morphometric changes. The results of both mRNA expression using PCR and immunohistochemistry showed a significant increase in AQP1, AQP3, and AQP7 expression in HFFD, whereas IF caused a decline in this expression. Conclusion: These findings suggest that IF can reduce inflammation, and oxidative stress and restore jejunal morphology caused by HFFD.

Turmeric Extract-loaded Selenium Nanoparticles Counter Doxorubicin-induced Hepatotoxicity in Mice via Repressing Oxidative Stress, Inflammatory Cytokines, and Cell Apoptosis.

BACKGROUND: Doxorubicin (DOX) is an antitumor anthracycline used to treat a variety of malignancies; however, its clinical use is associated with noticeable hepatotoxicity. Therefore, the current study was designed to delineate if biosynthesized SeNPs with turmeric extract (Tur-SeNPs) could alleviate DOX-induced hepatic adverse effects. METHODS: Mice were orally post-treated with Tur extract, Tur-SeNPs, or N-acetyl cysteine after the intraperitoneal injection of DOX. RESULTS: Our findings have unveiled a remarkable liver attenuating effect in DOX-injected mice post-treated with Tur-SeNPs. High serum levels of ALT, AST, ALP, and total bilirubin induced by DOX were significantly decreased by Tur-SeNPs therapy. Furthermore, Tur-SeNPs counteracted DOX-caused hepatic oxidative stress, indicated by decreased MDA and NO levels along with elevated levels of SOD, CAT, GPx, GR, GSH, and mRNA expression levels of Nrf-2. Noteworthily, decreased hepatic IL-1ß, TNF-α, and NF-κB p65 levels in addition to downregulated iNOS gene expression in Tur-SeNPs-treated mice have indicated their potent antiinflammatory impact. Post-treatment with Tur-SeNPs also mitigated the hepatic apoptosis evoked by DOX injection. A liver histological examination confirmed the biochemical and molecular findings. CONCLUSIONS: In brief, the outcomes have demonstrated Tur loaded with nanoselenium to successfully mitigate the liver damage induced by DOX via blocking oxidative stress, and inflammatory and apoptotic signaling.

Mitigating Aflatoxin B1-Induced Growth Impairment and Hepatic Stress in Nile Tilapia (Oreochromis niloticus): Comparative Efficacy of Saccharomyces cerevisiae and Silicate-Based Detoxifiers.

The objective of this study was to detect the effects of acute aflatoxin B1 (AFB1) exposure in Nile tilapia (Oreochromis niloticus) and the effectiveness of Saccharomyces cerevisiae and silicate in reducing these effects. Two hundred and forty Nile tilapia fingerlings (16 ± 0.5 g) were randomly assigned to four experimental groups, each with 60 fish and three replicates. Control basal diet (Diet 1) and three test diets were formulated, where Diet 2 was supplemented with 200 ppb AFB1. Diets 3 and 4 were intoxicated with AFB1 (200 ppb) and supplemented with 0.5% S. cerevisiae or 0.5%, respectively. After 60 days, Diet 1 had considerably greater growth characteristics than the other groups (p < 0.05). Diet 2 revealed a reduced (p < 0.05) survival rate after 1 month of exposure. In addition, Diet 1 showed higher (p < 0.05) total protein and albumin levels than Diets 3 and 4. AFB1 residues were detected in the liver in fish-fed Diet 2, Diet 4, and Diet 3. Alanine aminotransferase, aspartate aminotransferase, creatinine, and urea levels increased (p < 0.05) in fish-fed Diet 2. The glutathione peroxidase, lysozyme, and catalase activity were decreased (p < 0.05) in the fish-fed Diet 2. The malondialdehyde level was significantly higher in fish given Diet 2 (p < 0.05) than in fish-fed Diets 3 and 4. Histopathological investigation of fish-fed Diet 2 revealed impaired liver and spleen; however, both treatments (Diets 3 and 4) successfully lowered inflammation and preserved liver and spleen integrities. In conclusion, AFB1 impaired growth performance and posed a severe health risk to Nile tilapia. Furthermore, S. cerevisiae alleviated the contamination of AFB1 effects more efficiently than silicate employed for toxin adsorption.

Resistomycin Suppresses Prostate Cancer Cell Growth by Instigating Oxidative Stress, Mitochondrial Apoptosis, and Cell Cycle Arrest.

Globally, prostate cancer is among the most threatening and leading causes of death in men. This study, therefore, aimed to search for an ideal antitumor strategy with high efficacy, low drug resistance, and no or few adverse effects. Resistomycin is a natural antibiotic derived from marine actinomycetes, and it possesses various biological activities. Prostate cancer cells (PC3) were treated with resistomycin (IC12.5: 0.65 or IC25: 1.3 µg/mL) or 5-fluorouracil (5-FU; IC25: 7 µg/mL) for 24 h. MTT assay and flow cytometry were utilized to assess cell viability and apoptosis. Oxidative stress, apoptotic-related markers, and cell cycle were also assessed. The results revealed that the IC50 of resistomycin and 5-FU on PC3 cells were 2.63 µg/mL and 14.44 µg/mL, respectively. Furthermore, treated cells with the high dose of resistomycin showed an increased number of apoptotic cells compared to those treated with the lower dose. Remarkable induction of reactive oxygen species generation and lactate dehydrogenase (LDH) leakage with high malondialdehyde (MDA), carbonyl protein (CP), and 8-hydroxyguanosine (8-OHdG) contents were observed in resistomycin-treated cells. In addition, marked declines in glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in PC3 cells subjected to resistomycin therapy were observed. Resistomycin triggered observable cell apoptosis by increasing Bax, caspase-3, and cytosolic cytochrome c levels and decreasing Bcl-2 levels. In addition, notable downregulation of proliferating cell nuclear antigen (PCNA) and cyclin D1 was observed in resistomycin-treated cancerous cells. According to this evaluation, the antitumor potential of resistomycin, in a concentration-dependent manner, in prostate cancer cells was achieved by triggering oxidative stress, mitochondrial apoptosis, and cell cycle arrest in cancer cells. In conclusion, our investigation suggests that resistomycin can be considered a starting point for developing new chemotherapeutic agents for human prostate cancer.

Differential cellular localization of lectins in the testes of dromedary camel (Camelus dromedarius) during active and inactive breeding seasons.

The reproductive activity of the male dromedary camel (Camelus dromedarius) as a seasonal breeder is affected by various seasonal changes that reflect on the reproductive performance. In the current study, we explored a differential cellular localization of lectins in eight dromedary camel testes utilizing lectin histochemistry (LHC). The glycoconjugates' localizations were detected within the testicular tissue utilizing 13 biotin-labeled lectins (PNA, ConA, LCA, RCA120, GS IB4, WGA, BPL, DBA, ECA, PHA-E4, UEA-1, PTL-II, and SBA) distributed into six sets. The cellular structures revealed diverse lectins distribution that may reflect various glycoproteins' structures and their compositional modifications during spermatogenesis. Some of the investigated lectins were restricted to acrosomes of spermatids that will help study different stages during the spermatogenic cycle of dromedary camel, particularly PNA, and ECA. The statistical analysis showed a marked positive correlation between the response intensity of various lectins and the breeding season (P < 0.05). We can conclude that lectins have a fundamental role during camel spermatogenesis and are associated with the reproductive activity of dromedary camel.

Modulation of inflammatory, oxidative, and apoptotic stresses mediates the renoprotective effect of daidzein against glycerol-induced acute kidney injury in rats.

Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1ß (IL-1ß), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis.

Macro, Micro, and Nano-Inspired Bioactive Polymeric Biomaterials in Therapeutic, and Regenerative Orofacial Applications.

Introducing dental polymers has accelerated biotechnological research, advancing tissue engineering, biomaterials development, and drug delivery. Polymers have been utilized effectively in dentistry to build dentures and orthodontic equipment and are key components in the composition of numerous restorative materials. Furthermore, dental polymers have the potential to be employed for medication administration and tissue regeneration. To analyze the influence of polymer-based investigations on practical medical trials, it is required to evaluate the research undertaken in this sector. The present review aims to gather evidence on polymer applications in dental, oral, and maxillofacial reconstruction.

Therapeutic activity of green synthesized selenium nanoparticles from turmeric against cisplatin-induced oxido-inflammatory stress and cell death in mice kidney.

Cisplatin (CDDP) is a commonly prescribed chemotherapeutic agent; however, its associated nephrotoxicity limits its clinical efficacy and sometimes requires discontinuation of its use. The existing study was designed to explore the reno-therapeutic efficacy of turmeric (Tur) alone or conjugated with selenium nanoparticles (Tur-SeNPs) against CDDP-mediated renal impairment in mice and the mechanisms underlying this effect. Mice were orally treated with Tur extract (200 mg/kg) or Tur-SeNPs (0.5 mg/kg) for 7 days after administration of a single dose of CDDP (5 mg/kg, i.p.). N-acetyl cysteine NAC (100 mg/kg) was used as a standard antioxidant compound. The results revealed that Tur-SeNPs counteracted CDDP-mediated serious renal effects in treated mice. Compared with the controls, Tur or Tur-SeNPs therapy remarkably decreased the kidney index along with the serum levels of urea, creatinine, Kim-1, and NGAL of the CDDP-injected mice. Furthermore, Tur-SeNPs ameliorated the renal oxidant status of CDDP group demonstrated by decreased MDA and NO levels along with elevated levels of SOD, CAT, GPx, GR, GSH, and gene expression levels of HO-1. Noteworthy, lessening of renal inflammation was exerted by Tur-SeNPs via lessening of IL-6 and TNF-α besides down-regulation of NF-κB gene expression in mouse kidneys. Tur-SeNPs treatment also restored the renal histological features attained by CDDP challenge and hindered renal apoptosis through decreasing the Bax levels and increasing Bcl-2 levels. Altogether, these outcomes suggest that the administration of Tur conjugated with SeNPs is effective neoadjuvant chemotherapy to guard against the renal adverse effects that are associated with CDDP therapy.

Therapeutic role of mesenchymal stem cells and platelet-rich plasma on skin burn healing and rejuvenation: A focus on scar regulation, oxido-inflammatory stress and apoptotic mechanisms.

Cell-based therapies have great promise in accelerating and improving burn wound healing. It is a growing need to scale their competence to meet the clinical demands. In this study, the bone marrow mesenchymal stem cells (BMSCs) and platelet-rich plasma (PRP) were tested on the repair of induced burn wounds in a murine model. After the induction of thermal injury, rats were injected with BMSCs and/or PRP in the burn area. After 4 weeks of post-burn, our findings revealed that local treatment of burnt skin with BMSCs and/or PRP offered substantial outcomes when compared with the untreated group. Injected burn with BMSCs and/or PRP enhanced the wound contraction rate and decreased the burn area and period of epithelization. Significant increases in VEGF together with declines in MMP-9 and TGF-ß1 were observed in burnt areas after being treated with BMSCs and/or PRP therapy that indicated improved angiogenesis, and re-epithelization. Furthermore, both MSCs and PRP modulated the burn's oxidative and inflammatory microenvironment as indicated by increases in SOD, CAT, and GSH besides declines in MDA, IL-6, TNF-α, NF-κB, NO, and iNOS. Notable increases in Bcl-2 levels and decreases in Cas-3 and Bax levels were recorded in burnt skin that received both agents concomitantly. Interestingly, the histopathological examination validates the healing power of BMSCs and/or PRP. Collectively, BMSCs and PRP have pioneered therapeutics candidates for clinical application in burn healing possibly via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms along with regulating angiogenesis and scar formation.

Nootkatone Mitigated Melamine-Evoked Hepatotoxicity by Featuring Oxidative Stress and Inflammation Interconnected Mechanisms: In Vivo and In Silico Approaches.

Melamine (ML) is a common environmental contaminant, commonly used in food fraud, representing a serious health hazard and jeopardizing human and animal health. Recently, nootkatone (NK), a naturally occurring sesquiterpenoid, has garnered considerable attention due to its potential therapeutic advantages. We investigated the potential mechanisms underlying the protective effects of NK against ML-induced liver injury in rats. Five groups were utilized: control, ML, NK10, ML-NK5, and ML-NK10. ML induced substantial hepatotoxicity, including considerable alterations in biochemical parameters and histology. The oxidative distress triggered by ML increased the generation of malondialdehyde (MDA) and nitric oxide (NO) and decreased levels of reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. In addition, decreased expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and increased nuclear factor kappa beta (NF-κB) expression levels were observed in hepatocytes, which indicated the occurrence of inflammatory changes following ML exposure. These alterations were alleviated by NK supplementation in a dose-dependent manner. The data revealed that the favorable effects of NK were attributed, at least in part, to its antioxidant and anti-inflammatory properties. Moreover, our results were supported by molecular docking studies that revealed a good fit and interactions between NK and antioxidant enzymes. Thus, the current study demonstrated that NK is a potential new food additive for the prevention or treatment of ML-induced toxicity.

Biosynthesized Selenium Nanoparticles Using Epigallocatechin Gallate Protect against Pentylenetetrazole-Induced Acute Epileptic Seizures in Mice via Antioxidative, Anti-Inflammatory, and Anti-Apoptotic Activities.

Several negative outcomes are associated with current anti-epileptic medications. Epigallocatechin gallate (EGCG) is a plant-derived compound called catechin and has many medicinal activities, such as anti-inflammatory and antioxidant activities. Biosynthesized selenium nanoparticles are also showing their neuroprotective effect. The anti-epileptic effect of EGCG, alone or with SeNPs, is still debated. Here, we aimed to investigate the potential anti-seizure effect of biosynthesized SeNPs using EGCG (EGCG-SeNPs) against epileptic seizures and hippocampal damage, which is enhanced by pentylenetetrazole (PTZ) injection in mice. Mice were grouped as follows: control; PTZ-exposed group (epileptic model); EGCG + PTZ-treated group; sodium selenite (Na2SeO3) + PTZ-treated group; EGCG-SeNPs + PTZ-treated group; and valproic acid (VPA) + PTZ-treated group. EGCG-SeNPs administration showed anti-epileptic activity by increasing the latency time and reducing the seizure duration following the PTZ injection. Additionally, EGCG-SeNPs counteracted the PTZ-induced changes in oxidants and antioxidants. Moreover, EGCG-SeNPs inhibited the inflammatory response by suppressing the release of pro-inflammatory cytokines and decreasing the immunoreactivity of the glial fibrillary acidic protein and mRNA expression of glutamate receptor subunit zeta-1 (NMDAR; Grin1), showing their inhibitory effect on epilepsy-associated inflammation. Moreover, EGCG-SeNPs reduced PTZ-induced neuronal apoptosis, as indicated by a reduction in the levels of pro-apoptotic proteins and an elevation of the anti-apoptotic protein. Moreover, EGCG-SeNPs administration significantly modulated the PTZ-induced changes in monoamine levels and acetylcholinesterase activity in the hippocampal tissue. The obtained findings suggest the anti-seizure activity of EGCG-SeNPs via their antioxidant, anti-inflammatory, and anti-apoptotic effects, along with their neuromodulatory effect.

Sesquiterpene nootkatone counteracted the melamine-induced neurotoxicity via repressing of oxidative stress, inflammatory, and apoptotic trajectories.

Melamine (ML), a chemical substance of high nitrogen content, is used as a food adulterant. Former evidences implied that ML could induce a variety of toxic effects including neurotoxicity and cognitive impairment. Therefore, the aim of this study was to delineate the protective effect of the nootkatone (NK) against ML-induced neural adverse effects. Rats were orally pretreated with NK (5 and 10 mg/kg) prior to the oral administration of ML (700 mg/kg) for a period of 28 days. Our findings unveiled remarkable alleviating effect of NK on MK-induced neurobehavioral disturbance in open field test. Furthermore, NK lessened ML-caused increases in the acetylcholine esterase level in the brain tissue of exposed rats. NK also decreased the neural oxidative stress as represented by elevated levels of SOD, CAT, and GSH along with decreased MDA and NO levels. Upregulated mRNA expression levels of neural NRF-2 and HO-1 were noticed after NK administration. Remarkable anti-inflammatory impact was prominent by decreased neural IL-1ß, and TNF-α along with downregulated NF-κB and TLR-4 gene expression levels in NK-treated rats. Noteworthily, pre-treatment with NK decreased the immune reaction of RAGE and HMGB-1 induced by oral ML exposure. Brain histological examination validated the obtained biochemical and molecular results. To sum up, these outcomes reveal that NK successfully alleviated the neural damage induced by ML via blocking of oxidative stress, and inflammatory signaling pathways. Consequently, our study may suggest NK as a new effective therapeutic supplement for treatment of ML-mediated neurotoxicity in rats via inhibition of HMGB-1-RAGE/TLR-4/NF-κB.

Biochemical and histopathological effects of copper oxide nanoparticles exposure on the bivalve Chambardia rubens (Lamarck, 1819).

Copper nanoparticles are widely incorporated into many applications, including air and liquid filters, wood preservatives, batteries, thermal and electrical conductivity, inks and skin products. Their potential toxicity and environmental fate, however, are poorly studied in the freshwater bivalves. The aim of the present study was to evaluate the different effects of copper oxide nanoparticles and ionic copper on the digestive glands and gills of the mussel Chambardia rubens. Mussels were treated with 100 and 1000 µg Cu L-1 of copper oxide nanoparticles (CuONPs) or ionic copper (Cu2+) for 3, 7, and 14 days. The Cu accumulation and markers of oxidative stress in the digestive glands and gills were evaluated. The results show that the digestive gland collected higher levels of the two forms of copper than the gills. Exposure to CuONPs or Cu2+ induced significant elevations in superoxide dismutase, glutathione peroxidase and lipid peroxidation. Notably, a significant decrease was observed in the glutathione levels after exposure to both copper forms. CuONPs only induced a significant increase in glutathione reductase and glutathione S-transferase. The ionic copper only induced a significant decrease in catalase activities in the gill tissues. Overall, CuONPs and Cu2+ provoked oxidative stress, and further research is needed to clarify their genotoxic and neurotoxic effects on freshwater mussels and other biota.

Neuro-amelioration of Ficus lyrata (fiddle-leaf fig) extract conjugated with selenium nanoparticles against aluminium toxicity in rat brain: relevance to neurotransmitters, oxidative, inflammatory, and apoptotic events.

Aluminium is a non-essential metal, and its accumulation in the brain is linked with potent neurotoxic action and the development of many neurological diseases. This investigation, therefore, intended to examine the antagonistic efficacy of Ficus lyrata (fiddle-leaf fig) extract (FLE) conjugated with selenium nanoparticles (FLE-SeNPs) against aluminium chloride (AlCl3)-induced hippocampal injury in rats. Rats were allocated to five groups: control, FLE, AlCl3 (100 mg/kg), AlCl3 + FLE (100 mg/kg), and AlCl3 + FLE-SeNPs (0.5 mg/kg). All agents were administered orally every day for 42 days. The result revealed that pre-treated rats with FLE-SeNPs showed markedly lower acetylcholinesterase and Na+/K+-ATPase activities in the hippocampus than those in AlCl3 group. Additionally, FLE-SeNPs counteracted the oxidant stress-mediated by AlCl3 by increasing superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents in rat hippocampus. Besides, the formulated nanoparticles decreased the hippocampal malondialdehyde, carbonyl protein, and nitric oxide levels of AlCl3-exposed animals. Furthermore, FLE-SeNPs attenuated neural tissue inflammation, as demonstrated by decreased interleukin-1 beta, interleukin-6, nuclear factor kappa B, and glial fibrillary acidic protein. Remarkable anti-apoptotic action was exerted by FLE-SeNPs by increasing B cell lymphoma 2 and decreasing caspase-3 and Bcl-2-associated-X protein in AlCl3-exposed rats. The abovementioned results correlated well with the hippocampal histopathological findings. Given these results, SeNPs synthesized with FLE imparted a remarkable neuroprotective action against AlCl3-induced neurotoxicity by reversing oxidative damage, neuronal inflammation, and apoptosis in exposed rats.

Comparative neuroprotective effects of Cerebrolysin, dexamethasone, and ascorbic acid on sciatic nerve injury model: Behavioral and histopathological study.

Background: The majority of the suggested experimental modalities for peripheral nerve injury (PNI) result in varying degrees of recovery in animal models; however, there are not many reliable clinical pharmacological treatment models available. To alleviate PNI complications, research on approaches to accelerate peripheral nerve regeneration is encouraged. Cerebrolysin, dexamethasone, and ascorbic acid (vitamin C) drug models were selected in our study because of their reported curative effects of different mechanisms of action. Methodology: A total of 40 adult male albino rats were used in this study. Sciatic nerve crush injury was induced in 32 rats, which were divided equally into four groups (model, Cerebrolysin, dexamethasone, and vitamin C groups) and compared to the sham group (n = 8). The sciatic nerve sensory and motor function regeneration after crushing together with gastrocnemius muscle histopathological changes were evaluated by the sciatic function index, the hot plate test, gastrocnemius muscle mass ratio, and immune expression of S100 and apoptosis cascade (BAX, BCL2, and BAX/BCL2 ratio). Results: Significant improvement of the behavioral status and histopathological assessment scores occurred after the use of Cerebrolysin (as a neurotrophic factor), dexamethasone (as an anti-inflammatory), and vitamin C (as an antioxidant). Despite these seemingly concomitant, robust behavioral and pathological changes, vitamin C appeared to have the best results among the three main outcome measures. There was a positive correlation between motor and sensory improvement and also between behavioral and histopathological changes, boosting the effectiveness, and implication of the sciatic function index as a mirror for changes occurring on the tissue level. Conclusion: Vitamin C is a promising therapeutic in the treatment of PNI. The sciatic function index (SFI) test is a reliable accurate method for assessing sciatic nerve integrity after both partial disruption and regrowth.

Neuroprotective efficacy of the bacterial metabolite, prodigiosin, against aluminium chloride-induced neurochemical alternations associated with Alzheimer's disease murine model: Involvement of Nrf2/HO-1/NF-κB signaling.

Prodigiosin (PDG) is a bacterial metabolite with numerous biological and pharmaceutical properties. Exposure to aluminium is considered a root etiological factor in the pathological progress of Alzheimer's disease (AD). Here, in this investigation, we explored the neuroprotective potential of PDG against aluminium chloride (AlCl3 )-mediated AD-like neurological alterations in rats. For this purpose, rats were gavaged either AlCl3 (100 mg/kg), PDG (300 mg/kg), or both for 42 days. As a result of the analyzes performed on the hippocampal tissue, it was observed that AlCl3 induced biochemical, molecular, and histopathological changes like those related to AD. PDG pre-treatment significantly decreased acetylcholinesterase activity and restored the levels of brain-derived neurotrophic factor, monoamines (dopamine, norepinephrine, and serotonin), and transmembrane protein (Na+ /K+ -ATPase). Furthermore, PDG boosted the hippocampal antioxidant capacity, as shown by the increased superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents. These findings were accompanied by decreases in malondialdehyde and nitric oxide levels. The antioxidant effect may promote the upregulation of the expression of antioxidant genes (Nrf2 and HO-1). Moreover, PDG exerted notable anti-inflammatory effects via the lessening of interleukin-1 beta, tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor kappa B, and decreases in the gene expression of inducible nitric oxide synthase. In addition, noteworthy decreases in pro-apoptotic (Bax and caspase-3) levels and increases in anti-apoptotic (Bcl-2) biomarkers suggested an anti-apoptotic effect of PDG. In support, the hippocampal histological examination validated the aforementioned changes. To summarize, the promising neuromodulatory, antioxidative, anti-inflammatory, and anti-apoptotic activities of PDG establish it as a potent therapeutic option for AD.

Therapeutic antischizophrenic activity of prodigiosin and selenium co-supplementation against amphetamine hydrochloride-induced behavioural changes and oxidative, inflammatory, and apoptotic challenges in rats.

Schizophrenia (SCZ), a multifactorial neuropsychiatric disorder, is treated with inefficient antipsychotics and linked to poor treatment outcomes. This study, therefore, investigated the combined administration of prodigiosin (PDG) and selenium (Na2SeO3) against SCZ induced by amphetamine (AMPH) in rats. Animals were allocated into four groups corresponding to their respective 7-day treatments: control, AMPH (2 mg/kg), PDG (300 mg/kg) + Na2SeO3 (2 mg/kg), and AMPH + PDG + Na2SeO3. The model group exhibited biochemical, molecular, and histopathological changes similar to those of the SCZ group. Contrastingly, co-administration of PDG and Na2SeO3 significantly increased the time for social interaction and decreased AChE and dopamine. It also downregulated the gene expression of NMDAR1 and restored neurotrophin (BDNF and NGF) levels. Further, PDG combined with Na2SeO3 improved the antioxidant defence of the hippocampus by boosting the activities of SOD, CAT, GPx, and GR. These findings were accompanied by an increased GSH, alongside decreased MDA and NO levels. Furthermore, schizophrenic rats having received PDG and Na2SeO3 displayed markedly lower IL-1ß and TNF-α levels compared to the model group. Interestingly, remarkable declines in the Bax (pro-apoptotic) and increases in Bcl-2 (anti-apoptotic) levels were observed in the SCZ group that received PDG and Na2SeO3. The hippocampal histological examination confirmed these changes. Collectively, these findings show that the co-administration of PDG and Na2SeO3 may have a promising therapeutic effect for SCZ. This is mediated by mechanisms related to the modulation of cholinergic, dopaminergic, and glutaric neurotransmission and neurotrophic factors, alongside the suppression of oxidative damage, neuroinflammation, and apoptosis machinery.

Protective effect of quercetin against 5-fluorouracil-induced cardiac impairments through activating Nrf2 and inhibiting NF-κB and caspase-3 activities.

5-Fluorouracil (5-FU) is a chemotherapy used to treat many types of cancer. Cardiotoxicity is one of the common drawbacks of 5-FU therapy. Quercetin (Qu) is a bioflavonoid with striking biological activities. This research aimed to assess the ameliorative effect of Qu against 5-FU-mediated cardiotoxicity. Thirty-five rats were allocated into five groups: control group (normal saline), 5-FU group (30 mg/kg, intraperitoneally), Qu group (50 mg/kg, oral), 25 mg/kg Qu+5-FU group, and 50 mg/kg Qu+5-FU. The experimental animals were received the above-mentioned drugs for 21 days. Results showed that 5-FU significantly elevated creatine kinase, lactate dehydrogenase, serum cholesterol and triglyceride, and upregulated troponin and renin mRNA expression. Additionally, cardiac oxidant/antioxidant imbalance was evident in elevated oxidants (malondialdehyde and nitric oxide) and depleted antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). 5-FU also downregulated the gene expression of nuclear factor erythroid 2-related factor 2. Furthermore, 5-FU significantly increased cardiac pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and upregulated gene expression of nuclear factor kappa-B. 5-FU significantly enhanced cardiac apoptosis through upregulating caspase-3 expression and downregulating B-cell lymphoma 2. Immunohistochemical and histopathological examinations verified the above-mentioned findings. However, all these changes were significantly ameliorated in Qu pre-administered rats. Conclusively, Qu counteracted 5-FU-mediated cardiotoxicity through potent antioxidant, anti-inflammatory, and anti-apoptotic effects.

Thymoquinone counteracts oxidative and inflammatory machinery in carrageenan-induced murine paw edema model.

Thymoquinone (TQ) is an active constituent in Nigella sativa (black cumin) and is extensively reported for its distinguished antioxidant and anti-inflammatory bioactivities. Despite the local protective response of acute inflammation, it contributes to the development of various disease conditions such as cell death, organ damage, or carcinogenesis. Hence, in this study, the effects of orally administered TQ (50 mg/kg and 100 mg/kg) for 14 days against edema development, oxidative stress, and inflammation were investigated in paw edema induced by carrageenan in mice. Indomethacin (10 mg/kg) was used as a reference drug. The results revealed that TQ reduced the paw edema volume in a time-dependent manner, attenuated acetic acid-provoked writhing movements, and reduced xylene-triggered ear edema. Hematological findings revealed marked normalization of altered counts of WBCs, and platelets. Furthermore, paw tissue levels of malondialdehyde and nitric oxide showed marked decreases together with increases in nuclear factor erythroid 2-related factor 2, glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase after TQ administration. Additionally, TQ decreased pro-inflammatory mediators, such as interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, C-reactive protein, myeloperoxidase, and nuclear factor kappa-B in the inflamed paw tissue. Moreover, appreciable decreases were recorded in cyclooxygenase-2 and its product prostaglandin E2 and the immune reaction of tumor necrosis factor-alpha in TQ-treated mice. Histopathological findings further validated the potential antiedematous, anti-inflammatory power of TQ in inflamed tissues. Conclusively, the results encourage the potent application of TQ to subside acute inflammatory events because of its striking antioxidant and anti-inflammatory properties in inflamed paw tissue.

Selenium-enriched yeast modulates the metal bioaccumulation, oxidant status, and inflammation in copper-stressed broiler chickens.

Copper (Cu) could be seriously hazardous when present at excessive levels, despite its vital contribution to various cellular processes. Selenium-enriched yeast (SeY) was reported to improve the health and metabolic status in broiler chicken. Hence, our study was endeavored to illustrate the mitigating efficacy of SeY on Cu-induced hepatic and renal damage. Cobb chicks aged 1 day were allocated into four experimental groups and offered a basal diet, SeY (0.5 mg/kg), CuSO4 (300 mg/kg), or SeY plus CuSO4 in their diets for 42 days. Our results revealed that SeY supplement antagonized significantly the Cu accumulation in livers and kidneys of exposed birds. Marked declines were also detected in the AST, ALT, urea, and creatinine levels, besides marked increases in total protein, glycerides, and cholesterol in the SeY-supplemented group. Moreover, enhancement of cellular antioxidant biomarkers (superoxide dismutase, CAT, GPx, and GSH) along with lowered MDA contents were achieved by SeY in hepatic and renal tissues. Further, SeY exerted a noteworthy anti-inflammatory action as indicated by decreased inflammatory biomarkers (IL-1ß and TNF-α) and NO levels in both organs. Noticeable histopathological alterations of both organs further validated the changes in the markers mentioned above. To sum up, our findings indicate that SeY can be considered a potential feed supplement for alleviating Cu-induced hepatic and renal damage in broilers, possibly via activation of antioxidant molecules and lessening the inflammatory stress.