Hydroxyurea (HDU) is a widely used medication for various malignancies, thalassemia, and sickle cell anemia with reported side effects. The current study investigated HDU- induced hepatic injury and ...the protective potential of the royal jelly (RJ) against this hepatotoxic effect in the light of hepatic oxidative/ antioxidative status, pro-inflammatory cytokine, apoptosis signaling pathway, and histopathology. Sixty albino rats were used (n = 10/group) for 60 days: control, RJ (100 mg/kg body weight, orally), HDU (225 mg/kg body weight, orally), 2HDU (450 mg/kg body weight, orally), and HDU + RJ groups. HDU-treated rats showed significant elevation of liver function tests as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, as well as malondialdehyde and nitric oxide (oxidative biomarkers) and significant decreased hepatic antioxidant molecules (reduced glutathione, superoxide dismutase, and glutathione peroxidase), compared to a control group, that more pronounced in the high dose of HDU. In addition, HDU induced significant upregulation of TNF-α and the Caspase-3 apoptotic pathway. Moreover, the liver of HDU treated groups showed various hepatic lesions from mild to severe necrotic changes related to the HDU dose. However, administration of RJ with HDU improved liver function tests, liver histology, and hepatic oxidative/antioxidative status concerning HDU groups. Furthermore, oral RJ administration with HDU significantly lessens the immune-expression area % of TNF-α and Caspase-3. Thus, the royal jelly has antioxidant, anti-inflammatory, and anti-apoptotic properties against HDU- induced hepatic injury and could be, therefore, used as adjuvant therapy in patients with long-term HDU medication.
This study investigated
nanoparticles (NSP) to overcome sorafenib resistance in diethyl nitrosamine-induced hepatocellular carcinoma (HCC) in rats. This study used sixty Wistar male rats randomly ...grouped into two main groups, the normal control group, and the HCC model. For the normal control group (
= 12), animals were injected i.p. with PBS two times/week for 16 weeks. The remaining 48 rats were injected i.p. with using a single dose of diethyl nitrosamine (DENA) (200 mg/kg, ip), followed by phenobarbital sodium (0.05%) in drinking water for 16 weeks. At the end of the 16th week, rats were allocated into four groups (11 rats/each), one group was left without treatment (DENA group), and the other three groups were treated with either sorafenib (30 mg/kg; p.o.) or
Nanoparticles (NSP) (0.5 mg/kg body weight) once daily orally with the aid of gastric gavage or their combination for another four weeks. Blood and tissue samples were collected for further biochemical, histological, immunohistochemical, and gene expression analysis. Our result revealed that DENA-treated rats showed a marked elevation of hepatic enzyme markers with an increase in the total protein and globulin and decreases in the hepatic SOD. Catalase and GSH, with significantly increased MDA levels, subsequently increased the tumor biomarkers (AFP and CEA). On the molecular level, the DENA-treated rats showed significant up-regulation of Cyp19 mRNA and the inflammatory cytokines (TNF-α, iNOS, and TGF-1β) as well as the Ki-67 gene expression (
< 0.05) with down-regulation of the PPAR-γ and FOXO-1. In addition, the HCC group showed a loss of hepatic architecture, as well as atypia, swelling, macrosteatosis of hepatocytes, and fibrosis, besides increased vascularization. The immunohistochemical findings show increased expression of both GPC-3 and Hep Par 1 in the HCC group. SOR, NSP, or a combination of NSP and SOR.NSP treatment significantly overturned the DENA's harmful effect near the normal levels and restored all cancer biomarkers and antioxidant activities, indicating the chemotherapeutic impact of NSP. The present study provides evidence that NSP exerts a major anticancer effect on DENA-induced HCC. SOR/NSP is a promising combination for tumor suppression and overcoming sorafenib resistance in HCC by modulating antioxidants, anti-inflammatory signals, and tumor markers.
The importance of B complex vitamins starts early in the human life cycle and continues across its different stages. At the same time, numerous reports have emphasized the critical role of adequate B ...complex intake. Most studies examined such issues concerning a specific vitamin B or life stage, with the majority reporting the effect of either excess or deficiency. Deep insight into the orchestration of the eight different B vitamins requirements is reviewed across the human life cycle, beginning from fertility and pregnancy and reaching adulthood and senility, emphasizing interactions among them and underlying action mechanisms. The effect of sex is also reviewed for each vitamin at each life stage to highlight the different daily requirements and/or outcomes. Thiamine, riboflavin, niacin, pyridoxine, and folic acid are crucial for maternal and fetal health. During infancy and childhood, B vitamins are integrated with physical and psychological development that have a pivotal impact on one’s overall health in adolescence and adulthood. A higher intake of B vitamins in the elderly is also associated with preventing some aging problems, especially those related to inflammation. All supplementation should be carefully monitored to avoid toxicity and hypervitaminosis. More research should be invested in studying each vitamin individually concerning nutritional disparities in each life stage, with extensive attention paid to cultural differences and lifestyles.
A progressively essential bird of high economic significance for meat production and commercial egg is the Japanese quail, and so more experiments are necessary to improve the productivity of these ...birds under stressful encounters. The current work was performed to define the influences of Coenzyme Q10 (CoQ10) on growth, sexual behavior, and testicular characteristics (size of the gonad, traits of spermatic features, levels of plasma testosterone, steroidogenic-related gene expression) of Japanese quail (Coturnix coturnix japonica) aganist cadmium (Cd) administration. Chicks of quail (n = 250), 14 days old of age were distributed into 4 groups: basal ration (Group 1), basal ration and CoQ10 at 100 mg/kg ration (Group 2), basal ration and Cd at 50 mg/kg ration (Group 3), and CoQ10 + Cd (Group 4). Several parameters relating to productive performance, such as weight of the body, weight gain, feed intake, and the conversion ratio of feed, were evaluated. Constant visual scanning of the quails was performed to observe their sexual behaviors. Sperm characteristics, plasma testosterone levels, and testicular inflammatory markers of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also determined. Oxidative-antioxidant redox status in the testes was evaluated by analyzing MDA level, GPx, and SOD activities. Steroidogenic-related gene expression in the testes (CYP17A1, StAR, 3β-HSD, and Cyp19) was also examined. In addition, testicular apoptosis was assessed by monitoring the alterations in the local expression of stress-induced (HSP70), proteins of anti-apoptotic marker (Bcl-2), and pro-apoptotic markers (caspase-3 and Bax). Cd administration hurts body performance, sexual behavior, and testicular efficiency parameters.
Interestingly, CoQ10 supplementation improved reproductive performance. Moreover, it significantly increases the % of birds exhibiting sexual behavior and enhances testicular functions, which were damaged by Cd administration, by enhancing plasma testosterone level, antioxidative enzyme activity, and sperm quality traits while reducing the MDA and pro-inflammatory markers. Furthermore, downregulation of pro-apoptotic factor expression, though it increased the expression of the anti-apoptotic protein, was recorded. Correspondingly, CoQ10 revealed a marked upregulation in the expression of steroidogenic-related genes. Conclusion: It is established that the consumption of CoQ10 in the ration of Japanese quail, following a Cd adminstration, improves productive performance, sexual behavior, and several testicular function parameters as a potent antioxidant.
The expanding uses of carbon nanotubes (CNTs) in industry and medicine have raised concerns about their toxicity on human and animal health. CNTs, including multi-walled nanotubes (MWCNTs), have been ...reported to induce immunotoxic, inflammatory, and oxidative effects. Quercetin is a natural flavonoid present in many vegetables and fruits and has immunomodulatory, anti-inflammatory, and antioxidant properties. Herein, we investigated the protective effects of quercetin on pristine MWCNTs-induced immunotoxicity in mice. In comparison with two doses of MWCNTs, high doses 0.5 mg/kg body weight (BW), once intraperitoneally (IP) caused higher immunotoxic, inflammatory, and oxidative effects than low doses (0.25 mg/kg BW, once IP). Administration of quercetin (30 mg/kg BW, IP for 2 weeks) relieved these deleterious effects as evidenced by (1) reduced spleen weight, (2) increased number of total leukocytes, lymphocytes, and neutrophils, (3) elevated serum levels of IgM, IgG, and IgA, (4) decreased lipid peroxide malondialdehyde levels and increased levels of antioxidant markers reduced glutathione, superoxide dismutase, and catalase in the spleen, (5) decreased concentrations and mRNA levels of inflammatory markers tumor necrosis factor-alpha (TNFα), interleukin 1 beta (IL1ß), and IL6 in the spleen, (6) downregulated expression of immunomodulatory genes transforming growth factor-beta (TGFß), cyclooxygenase2 (COX2), and IL10, and (7) regenerative histological changes as indicated by decreased mononuclear cell infiltration, minimized degenerative changes and restored lymphocytes depletion in the spleen. These results infer that quercetin can ameliorate MWCNTs-induced immunotoxic, inflammatory, and oxidative effects.
Aflatoxins (AFs) are the most detrimental mycotoxin, potentially hazardous to animals and humans. AFs in food threaten the health of consumers and cause liver cancer. Therefore, a safe, efficient, ...and friendly approach is attributed to the control of aflatoxicosis. Therefore, this study aimed to evaluate the impacts of
(CLV) on hepatic aflatoxicosis, aflatoxin residues, and meat quality in quails. Quails were allocated into a control group; the CLV group received CLV (1 g/kg diet); the AF group received an AF-contaminated diet (50 ppb); and the AF+CLV group received both treatments. The results revealed that AF decreased the growth performance and caused a hepatic injury, exhibited as an increase in liver enzymes and disrupted lipid metabolism. In addition, AF induced oxidative stress, exhibited by a dramatic increase in the malondialdehyde (MDA) level and decreases in glutathione (GSH) level, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Significant up-regulation in the inflammatory cytokine (TNF-α, IL-1β, and IL-6) mRNA expression was also documented. Moreover, aflatoxin residues were detected in the liver and meat with an elevation of fat% alongside a decrease in meat protein%. On the other hand, CLV supplementation ameliorated AF-induced oxidative stress and inflammatory condition in addition to improving the nutritional value of meat and significantly reducing AF residues. CLV mitigated AF-induced hepatic damage, decreased growth performance, and lowered meat quality via its antioxidant and nutritional constituents.
Researchers are constantly searching for drugs to combat the coronavirus pandemic caused by SARS-CoV-2, which has lasted for over two years. Natural compounds such as phenolic acids are being tested ...against Mpro and AAK1, which are key players in the SARS-CoV-2 life cycle. This research work aims to study the ability of a panel of natural phenolic acids to inhibit the virus's multiplication directly through Mpro and indirectly by affecting the adaptor-associated protein kinase-1 (AAK1). Pharmacophore mapping, molecular docking, and dynamic studies were conducted over 50 ns and 100 ns on a panel of 39 natural phenolic acids. Rosmarinic acid (16) on the Mpro receptor (- 16.33 kcal/mol) and tannic acid (17) on the AAK1 receptor (- 17.15 kcal/mol) exhibited the best docking energy against both receptors. These favourable docking score values were found to be superior to those of the co-crystallized ligands. Preclinical and clinical research is required before using them simultaneously to halt the COVID-19 life cycle in a synergistic manner.
The food industry produces large quantities of waste, which is available in bulk at zero cost. This study aimed to investigate a new method to maximize the protein intake from pea peels and its ...further utilization as a value-added food ingredient to produce healthy snack crackers and dry soup. Dehydrated green curd of pea peel (DGCPp) with high protein content (35%) was prepared and incorporated into snack cracker and instant soup powder. Wheat flour was substituted with DGCPp to prepare crackers at three substitution levels (5, 10, and 15%) compared to the cracker control sample (100% wheat flour). Increasing the level of this substitution improved the nutritional value of crackers, with highest protein content was in DGCPp crackers (15%). Crackers also had higher contents of mineral and essential amino acids. The physicochemical and sensorial properties of soup samples were significantly influenced by the addition of DGCPp. Higher rehydration value and mineral content (Ca, Mg, Fe, and Zn) were observed in DGCPp soup samples compared to the control sample. Soup samples of all proportions were more acceptable by all the panelists compared with the control sample. With these findings, it can be concluded that DGCPp can be utilized in a variety of food products (such as crackers and soups) with higher nutritive values.
Recently, we reported that quercetin (Que) could alleviate immunotoxicity induced by pristine multi-walled carbon nanotubes (MWCNTs) in mice. In the present study, we explored whether Que could also ...relieve MWCNTs-induced neurotoxicity. MWCNTs injection induced a dose-dependent neurotoxic effect in mice as evidenced by increased oxidative stress, inflammation, and pyroptosis in the brain. However, treatment with Que ameliorated MWCNTs-induced neurotoxicity as revealed by 1) elevated acetylcholinesterase (AChE) activity, 2) reduced lipid peroxidation biomarker malondialdehyde (MDA), 3) improved antioxidant status as indicated by increased levels of reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT), as well as upregulated expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes, 4) decreased levels and expression of inflammatory biomarkers nitric oxide (NO), interleukin 1 beta (IL1ß), tumor necrosis factor-alpha (TNFα), and nuclear factor kappa B (NF-κB), 5) downregulated expression of pyroptosis-related genes nod-like receptor protein inflammasome 3 (Nlrp3) and caspase 1 (Casp1) but with no effect on the apoptotic Casp3 gene, 6) minimized axonal degeneration and number of microglia in the cerebral medulla, and 7) diminished the number of degenerated neurons in hippocampus and cerebellum. Taken together, Que could ameliorate MWCNT-induced neurotoxicity through antioxidant, anti-inflammatory, and anti-pyroptotic mechanisms.
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•MWCNTs induced a dose-dependent neurotoxic effect in mice.•Quercetin induced ameliorated this neurotoxicity through elevation of AChE.•Quercetin also reduced MDA and improved antioxidant status.•Quercetin decreased inflammatory biomarkers (NO, IL1ß, TNFα, and NF-κB).•Quercetin downregulated expression of pyroptosis-related genes.•Quercetin also minimized neuronal and axonal degeneration.
The current study aimed to explore the possible prophylactic and therapeutic effect of Nigella sativa L. oil (NSO) against disruption of endocrine signals and injuries in the thyroid gland, ovary, ...and uterine tissues induced by sodium fluoride (NaF). Twenty-eight mature female Wistar rats were randomly allocated into four experimental groups (n = 7/group) as follows: control group; NaF group, orally received NaF (20 mg/kg b.wt.) daily; NSO/NaF, orally received NSO (300 mg/kg b.wt.) two weeks before being given NaF and continued throughout the experiment; and NSO+NaF group orally received NSO concurrently with NaF. Our results indicated that NSO restored hormonal balance and suppressed oxidative damage and inflammation. Moreover, the levels of triiodothyronine, thyroxine, thyroid peroxidase, estrogen (E2), progesterone, follicle-stimulating hormone, and luteinizing hormone were elevated, while prostaglandins F2-α and cortisol levels were decreased in NSO treated groups compared to NaF-intoxicated rats. As well, NSO significantly boosted levels of antioxidant molecules, and lowered lipid peroxidation of examined tissues, unlike NaF-treated group. NSO also up-regulated antioxidant enzymes, anti-apoptotic protein, zona pellucida sperm-binding protein, bone morphogenetic protein, and thyroid stimulating hormone, conversely down-regulated inflammatory cytokines, apoptotic proteins, estrogen receptor-α, estrogen receptor-β, and thyroid stimulating hormone receptors compared to NaF-intoxicated group. Additionally, NSO ameliorated tissue damage of the thyroid gland, ovary, and uterus induced by NaF. -Overall, the prophylactic group (NSO/NaF) performed better antioxidant and anti-inflammatory activities than the treated group almost in all examined tissues, which is reflected by the improvement in the structure of the thyroid, ovarian, and uterine tissues.
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•Sodium fluoride (NaF) caused hypothyroidism and reproductive dysfunction.•Nigella sativa L oil (NSO) possesses antioxidant potential toward NaF toxicity.•NSO enhances anti-inflammatory and antiapoptotic activity against NaF toxicity.•NSO upregulates ZP3, and Bmp15, while it downregulates TSHR and ER gene expression.•NSO improves thyroidal, ovarian, and uterine histological alterations.
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