Rutin Nanoparticles Alleviate Cadmium-Induced Oxidative and Immune Damage in Broilers' Bursa of Fabricius via Modulating Hsp70/TLR4/NF-κB Signaling Pathway.

Cadmium (Cd) is a serious environmental pollutant affecting various tissues/organs in broilers and compromising their immunological function and productivity. Therefore, the current study aimed to investigate Cd-induced immunotoxicity and potential immunoprotective effect of rutin nanoparticles (RNPs) in the bursal tissue of broilers. A total number of 150 chicks from the Hubbard breed were randomly divided into 5 groups. Group I was fed on standard basal diet (SD) with normal drinking water (DW), Group II received SD containing RNPs (50 mg/kg feed) with DW, Group III fed on SD and DW containing Cd (150 mg/L), Group IV co-treated with rutin-enforced SD (50 mg/kg diet) and DW containing Cd (150 mg/L), and finally, Group V co-supplemented with RNP-enhanced SD (50 mg/kg diet) DW containing Cd (150 mg/L). Productive performance, economic efficiency, oxidative biomarkers, histopathological changes, and the expression level of TLR-4, HSP-70, caspase 3, NF-κB, Bcl-2, and Bax were assessed in the BF tissue. Cd led to severe production and economic losses in exposed birds with a marked surge of oxidative biomarkers, pro-inflammatory cytokines, and histopathological changes in the bursal tissue which could be explained through upregulation of the Hsp70/TLR4/NF-κB molecular pathway in the BF tissue. Meanwhile, RNPs could alleviate most of these changes and prevail optimistic immunomodulatory properties which subsequently could enhance broilers' productivity when incorporated in their diets.

Neuroprotective effect of piracetam-loaded magnetic chitosan nanoparticles against thiacloprid-induced neurotoxicity in albino rats.

Thiacloprid (TH) is a neurotoxic agricultural insecticide and potential food contaminant. The purpose of this study was to investigate the relationship between TH exposure and memory dysfunction in rats, as well as the potential protective effect of piracetam and piracetam-loaded magnetic chitosan nanoparticles (PMC NPs). Rats were divided into five equal groups (six rats/group). The control group received saline. Group II was treated with PMC NPs at a dose level of 200 mg/kg body weight (Bwt); Group III was treated with 1/10 LD50 of TH (65 mg/kg Bwt); Group IV was treated with TH (65 mg/kg Bwt) and piracetam (200 mg/kg Bwt); Group V was co-treated with TH (65 mg/kg Bwt) and PMC NPs (200 mg/kg Bwt). All animal groups were dosed daily for 6 weeks by oral gavage. Footprint analysis, hanging wire test, open field test, and Y-maze test were employed to assess behavioral deficits. Animals were euthanized, and brain tissues were analyzed for oxidative stress biomarkers, proinflammatory cytokines, and gene expression levels of glial fibrillary acidic protein (GFAP), amyloid-beta precursor protein (APP), B-cell lymphoma 2 (Bcl-2), and caspase-3. Brain and sciatic nerve tissues were used for the evaluation of histopathological changes and immunohistochemical expression of tau protein and nuclear factor kappa B (NF-κB), respectively. The results revealed that TH-treated rats suffered from oxidative damage and inflammatory effect on the central and peripheral nerves. The administration of PMC NPs considerably protected against TH-induced neuronal damage, increased antioxidant enzyme activity, decreased inflammatory markers, and improved behavioral performance than the group treated with piracetam. The neuroprotective effect of PMC NPs was mediated through the inhibition of GFAP, APP, caspase-3, Tau, and NF-κB gene expression with induction of Bcl-2 expression. In conclusion, TH could induce oxidative stress, inflammatory and neurobehavior impairment in rats. However, PMC NPs administration markedly mitigated TH-induced brain toxicity, possibly via oxidative and inflammatory modulation rather than using piracetam alone.

Ameliorative Effect of Pomegranate Peel Extract (PPE) on Hepatotoxicity Prompted by Iron Oxide Nanoparticles (Fe2O3-NPs) in Mice.

An evaluation of the ameliorative effect of pomegranate peel extract (PPE) in counteracting the toxicity of iron oxide nanoparticles (Fe2O3-NPs) that cause hepatic tissue damage is focused on herein. Forty male albino mice were haphazardly grouped into four groups as follows: the first control group was orally gavage daily with physiological saline; the second group received 100 mg/kg of PPE by the oral route day after day; the third group received 30 mg/kg Fe2O3-NPs orally; and the fourth group received both PPE and Fe2O3-NPs by the oral route, the same as the second and third sets. Later, after the completion of the experiment, we collected the liver, blood, and bone marrow of bone specimens that were obtained for further laboratory tests. For instance, exposure to Fe2O3-NPs significantly altered serum antioxidant biomarkers by decreasing the levels of total antioxidant capacity (TAC), catalase (CAT), and glutathione s-transferase (GST). Additionally, it caused changes in the morphology of hepatocytes, hepatic sinusoids, and inflammatory Kupffer cells. Furthermore, they significantly elevated the number of chromosomal aberrations including gaps, breaks, deletions, fragments, polyploidies, and ring chromosomes. Moreover, they caused a significant overexpression of TIMP-1, TNF-α, and BAX mRNA levels. Finally, the use of PPE alleviates the toxicity of Fe2O3-NPs that were induced in the hepatic tissues of mice. It is concluded that PPE extract has mitigative roles against the damage induced by Fe2O3-NPs, as it serves as an antioxidant and hepatoprotective agent. The use of PPE as a modulator of Fe2O3-NPs' hepatotoxicity could be considered as a pioneering method in the use of phytochemicals against the toxicity of nanoparticles.

Immune-antioxidant trait, Aeromonas veronii resistance, growth, intestinal architecture, and splenic cytokines expression of Cyprinus carpio fed Prunus armeniaca kernel-enriched diets.

Currently, the intervention of plant by-products in the fish diet has gained tremendous attention owing to the economic and high nutritious value. The current study is a pioneer attempt to incorporate the apricot, Prunus armeniaca kernel powder (PAKP) into the Common carp, Cyprinus carpio diets, and assess its efficacy on growth, digestion, intestinal morphology, immunity, antioxidant capacity, and splenic cytokines expression, besides the antibacterial role against Aeromonas veronii infection. Apparently healthy fish (N = 120) with an initial body weight of 24.76 ± 0.03g were allotted in 12 glass aquaria (60 L) and randomly distributed into four groups (triplicates, 10 fish/aquarium). The control group (PAKP0) was fed a basal diet without additives. The second, third, and fourth groups were provided PAKP diets with various concentrations (2.5 (PAKP2.5), 5 (PAKP5), and 10 g kg-1 (PAKP10)) respectively. After 60 days (feeding trial), sub-samples of the fish (12 fish/group) were intraperitoneally injected with 1 × 107 CFU mL-1 of A. veronii. Results revealed that body weight gain, feed conversion ratio, and specific growth rates were significantly augmented in the PAKP10 group in comparison to the other groups. The dietary inclusion of PAKP at all concentrations boosted the digestive capacity and maintained the intestinal morphology (average villus length, villus width, and goblet cells count) with a marked improvement in PAKP10. Moreover, fish fed on PAKP10 followed by PAKP5 then PAKP2.5 diets had noticeably elevated values of immunological biomarkers (IgM, antiprotease, and lysozyme activity) and antioxidant capabilities (the total antioxidant capacity, superoxide dismutase, and reduced glutathione) as well as significant up-regulation of immune and antioxidant-related genes (TGF-ß2, TLR-2, TNF-α, IL-10, SOD, GPx, and GSS). Fourteen days post-infection with A. veronii, the highest relative percentage survival of fish was observed in PAKP10 (83.33%), followed by PAKP5 (66.67%), and PAKP2.5 (50%). Our results indicated that a dietary intervention with PAKP could promise growth, digestion, immunity, and protect C. carpio against A. veronii infection in a dose-dependent manner. This offers a framework for future application of such seeds as a growth promotor, immune-stimulant, and antioxidant, besides an alternative cheap therapeutic antibacterial agent for sustaining the aquaculture industry.

Mesenchymal stem-cells' exosomes are renoprotective in postmenopausal chronic kidney injury via reducing inflammation and degeneration.

Chronic kidney disease (CKD) is an important global disease its rates are increasing worldwide. CKD is caused by injuries to kidney tissue that exceeds the rate of regeneration, which with time lead to irreversible renal damage and CKD become evident. In females, diminished estrogen supply in the postmenopausal period is associated with greater risk for developing CKD. In this study we isolated exosomes from bone marrow mesenchymal stem/stromal cells (BM-MSCs) and tested their therapeutic effects on post-menopause CKD (PM-CKD) and compared their effects with BM-MSCs. The menopause model was achieved by bilateral ovariectomy in 8-months-old female albino rats, then no treatment, 2 million BM-MSCs or 100 µg of exosomes (Exo) was given intravenously in tail vein to ovariectomized rats and the study continued for 8 weeks post-ovariectomy. Changes in weight, urine volume, urine protein content, kidney function biochemical parameters (creatinine and BUN), Kidney oxidative stress (MDA), kidney antioxidant parameters (SOD, GPx and CAT), histopathological changes, immunohistochemical expression of KIM-1 and, finally, genes related to renal damage (peroxiredoxin-3, KIM-1 and ICAM-1) and inflammation (TNF-α, Cox2 and IL-6) were recorded for all study groups. Post-ovariectomy there was an increased body weight, drastic reduction of estrogen and progesterone levels, reduced urine output, increased urinary protein excretion, elevated serum creatinine and BUN, increased MDA and reduced GPx SOD, and CAT in kidney tissue, chronic inflammation, degenerative and fibrotic lesions in histopathological examination, high expression of KIM-1 immunohistochemically and changes in gene expression analyses all pointing to the development of CKD in the study rats. In the PM-CKD groups receiving BM-MSCs or Exo, the whole chronic inflammatory picture was completely reversed towards a much normal kidney structure and function. The improvements were more observable with Exo compared to BM-MSCs. Overall, our results show for the first time that exosomes isolated from BM-MSCs are more potent in reducing chronic inflammatory changes in the kidney of postmenopausal females compared to the cell-based approach using BM-MSCs. Therefore, MSCs-derived exosomes are a promising therapeutic approach for preserving postmenopausal kidney structure and function and, subsequently, should improve the quality of life of postmenopausal females.

Effects of Rosemary Oil (Rosmarinus officinalis) supplementation on the fate of the transplanted human olfactory bulb neural stem cells against ibotenic acid-induced neurotoxicity (Alzheimer model) in rat.

Rosemary oil (ROO) is known to have multiple pharmacological effects: it is an antioxidant, anti-inflammatory, and cytoprotective. In the present study, we examined the effects of ROO on Human olfactory bulb neuronal stem cells (hOBNSCs) after their transplantation into rats, with the ibotenic (IBO) acid-induced cognitive deficit model. After 7 weeks, cognitive functions were assessed using the Morris water maze (MWM). After two months blood and hippocampus samples were collected for biochemical, gene expression, and histomorphometric analyses. Learning ability and memory function were significantly enhanced (P < 0.05) after hOBNSCs transplantation and were nearly returned to normal in the treated group. The IBO acid injection was associated with a significant decline (P < 0.05) of total leukocyte count (TLC) and a significant increase (P < 0.05) in total and toxic neutrophils. As well, the level of IL-1ß, TNF-α CRP in serum and levels of MDA and NO in hippocampus tissue were significantly elevated (P < 0.05), while antioxidant markers (CAT, GSH, and SOD) were reduced (P < 0.05) in treated tissue compared to controls. The administration of ROO before or with cell transplantation attenuated all these parameters. In particular, the level of NO nearly returned to normal when rosemary was administrated before cell transplantation. Gene expression analysis revealed the potential protective effect of ROO and hOBNSCs via down-expression of R-ßAmyl and R- CAS 3 and R-GFAP genes. The improvement in the histological organization of the hippocampus was detected after the hOBNSCs transplantation especially in h/ROO/hOBNSCs group.

Thiacloprid Induced Developmental Neurotoxicity via ROS-Oxidative Injury and Inflammation in Chicken Embryo: The Possible Attenuating Role of Chicoric and Rosmarinic Acids.

Insecticides are widely employed in agriculture to control pests and as major factors for enhancing crop productivity. Thiacloprid (TH) is one of the most-used insecticides worldwide. In this study, the negative impact of TH on the brain tissue of developing chicken embryo models and the modulatory effect of chicoric (CA) and rosmarinic (RA) acids were investigated. The eggs were injected in ovo with different doses of TH (0.1, 1, 10, and 100 µg/egg). TH significantly increased the oxidative damage in the brain of exposed embryos in a dose-dependent manner (p < 0.05). TH significantly elevated the oxidative stress markers; protein carbonyl, malondialdehyde content, and DNA damage (p < 0.05). Myeloperoxidase activity and nitric oxide significantly increased with overexpression of the pro-inflammatory cytokines (interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta) and stress-related and apoptotic genes (NF-KB, Caspase-3) in the brain tissue on both biochemical and molecular levels (p < 0.05), while downregulating the expression of antiapoptotic Bcl-2. Co-treatment of CA and RA with TH markedly decreased the insecticide-induced toxicity with a prominent synergistic effect (p < 0.05). In conclusion, TH is suggested to be a possible neurotoxic to embryos of vertebrates including human. The study also revealed the antioxidant, anti-inflammatory, genoprotective, and antiapoptotic property of CA and RA against TH toxicity.

Effects of sodium butyrate nanoparticles on the hemato-immunological indices, hepatic antioxidant capacity, and gene expression responses in Oreochromisniloticus.

Recently, nanotechnology has been greatly developed to provide the aquaculture industry with new beneficial nanomaterials to improve the health and welfare of aquatic animals. Herein, an eight-week experiment was designed to examine the dietary impacts of sodium butyrate nanoparticles (SB-NPs) on the hematological profile, blood proteins, immunological indices, antioxidant capacity, and expression analysis of cytokines and antioxidant-related genes in Oreochromis niloticus. Fish were randomly assigned into 5 experimental groups (3 replicates per group) and were fed diets supplemented with 5 levels of SB-NPs as 0.0 (control), 0.5, 1.0, 1.5, and 2.0 mg kg-1. The results revealed that supplementing diets with SB-NPs (1.0-2.0 mg kg-1) significantly elevated erythrocyte and leukocyte counts, hemoglobin concentrations, hematocrit values, total albumin, globulin, serum lysozyme activities, and total immunoglobulin M values compared with the control group. Notably, the highest levels of the parameters mentioned above were noticed in the group fed diet supplemented with 1.5 mg kg-1 SB-NPs. Moreover, dietary SB-NPs modulated the fish's antioxidant defense mechanisms, whereas there was a significant increase in hepatic superoxide dismutase, catalase, and glutathione peroxidase enzyme activities along with a significant decline in hepatic malondialdehyde concentrations in fish groups fed diets supplemented with SB-NPs (1.0-2.0 mg kg-1). A significant upregulation of antioxidant enzyme genes (gpx and sod), anti-inflammatory cytokine (il-10), and pro-inflammatory cytokines (il-1ß and il-8) were noticed in liver tissues of SB-NPs groups (0.5-1.5 mg kg-1). The highest mRNA expression folds of the above genes were recorded in the fish group fed diet supplemented with 1.5 mg kg-1 SB-NPs. In this context, we hypothesized that dietary supplementation with SB-NPs can boost the antioxidant status and immunity of O. niloticus. However, further research studies are still recommended.

Ginkgo biloba leaf extract improves growth, intestinal histomorphometry, immunity, antioxidant status and modulates transcription of cytokine genes in hapa-reared Oreochromis niloticus.

This study was designed to evaluate the impacts of dietary supplementation with Ginkgo biloba leaf extract (GBL) on the growth, intestinal histomorphometry, immunity, antioxidant status, and expression of cytokine genes in Nile tilapia reared in the hapas. A control diet was enriched with different GBL levels (0.0, 5.0, 7.0, and 9.0 g/kg) to form 4 experimental diets and were fed to Nile tilapia for 8 weeks. The findings illustrated that dietary GBL significantly enhanced the growth and feed utilization indices compared to those reared in the control group. A dose-dependent increase of hepatic catalase, superoxide dismutase, and glutathione peroxidase activities alongside a decline of hepatic malondialdehyde levels were recorded in GBL groups compared with the control. Serum lysozyme activity, complement C3, and immunoglobulin M levels were significantly increased in GBL groups compared with the control group. Moreover, dietary GBL maintained the normal intestinal and hepatopancreatic histological structures with a significant increase of some histomorphometric measurements of proximal, middle, and distal intestinal parts of the treated fish. Interestingly, dietary GBL supplementation significantly increased the mRNA expression of interleukin-1 beta (IL-1ß), IL-6, IL-10, tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) genes in the splenic tissues of treated fish over the control group. To conclude, it could be recommended to use GBL as a functional phytogenic feed additive to improve the growth, hepatic and intestinal health status, hepatic antioxidant status, and immunity of treated Nile tilapia. Besides, the second order polynomial regression revealed that 7.50 g GBL/kg diet is the optimal inclusion level to improve growth with no negative impacts on the overall health condition of treated Nile tilapia.

Synergistic effects of Ficus Carica extract and extra virgin olive oil against oxidative injury, cytokine liberation, and inflammation mediated by 5-Fluorouracil in cardiac and renal tissues of male albino rats.

5-Fluorouracil (5-FU), a chemotherapeutic drug, has adverse effects on heart and kidney functions. Ficus Carica (fig) and extra virgin olive oil (EVOO) are natural sources which have antioxidant effects. This study investigated the synergistic effects of fig extract and EVOO against cardiac and renal damage induced by 5-FU. Forty rats were equally divided into five groups and treated with physiological saline (control), five intravenous injections of 5-FU (40 mg/kg b.w) (5-FU), fig (1 g/kg b.w/day, orally) with 5-FU (Fig/5-FU), EVOO (7 g/kg b.w/day, orally) with 5-FU (EVOO/5-FU), combined treatment of fig and EVOO with five 5-FU injections (Fig/EVOO/5-FU). After 30 days, blood and tissue samples (Heart and kidney) were collected to be used in the examinations. 5-FU significantly increased serum creatine kinase activity, renal biomarkers, cholesterol, triglycerides, C-reactive protein, tumor necrosis factor-α, and interleukin-1ß as well as cardiac and renal lipid peroxides (malondialdehyde). Meanwhile, serum levels of immunoglobulins, interleukins (IL-10, IL-12), and antioxidants of heart and kidney tissues were significantly decreased in 5-FU group. It also downregulated cardiac and renal Bcl2, and upregulated cardiac troponin and renin gene expressions. As well, histological alterations clarified that 5-FU induced cardiac cell damage, distorted renal corpuscles and tubules, inflammatory cell infiltrations, and severe congestion and hemorrhage in the blood vessels. The treatment with fig and olive oil, especially the combined treatment, modulated the toxic effect of 5-FU on the heart and kidney. Our results revealed that fig extract and EVOO have a powerful antioxidant and many protective effects against cardiac and renal toxicity induced by 5-FU, especially when using fig and EVOO together as a combined treatment.