Modulatory mechanisms of copperII-albumin complex toward N-nitrosodiethylamine-induced neurotoxicity in mice via regulating oxidative damage, inflammatory, and apoptotic signaling pathways.

N-nitrosodiethylamine (ND) is an extremely toxic unavoidable environmental contaminant. CopperII-albumin (CuAB) complex, a newly developed Cu complex, showed antioxidant and anti-inflammatory potential. Hereby, we explored the plausible neuroprotective role of CuAB complex toward ND-evoked neurotoxicity in mice. Twenty-four male mice were sorted into 4 groups (6 mice each). Control group, mice were administered oral distilled water; and CuAB group, mice received CuAB complex at a dose of 817 µg/kg orally, three times weekly. In ND group, ND was given intraperitoneally (50 mg/kg body weight, once weekly for 6 w). CuAB+ND group, mice were administered a combination of CuAB and ND. The brain was quickly extracted upon completion of the experimental protocol for the evaluation of the oxidative/antioxidative markers, inflammatory cytokines, and histopathological examination. Oxidative stress was induced after ND exposure indicated by a reduction in GSH and SOD1 level, with increased MDA level. In addition, decreased expression of SOD1 proteins, Nrf2, and 5-HT mRNA expression levels were noticed. An apoptotic cascade has also been elicited, evidenced by overexpression of Cyt c, Cl. Casp 3. In addition, increased regulation of proinflammatory genes (TNF-α, IL-6, iNOS, Casp1, and NF-κB (p65/p50); besides, increment of protein expression of P-IKBα and reduced expression of IKBα. Pretreatment with CuAB complex significantly ameliorated ND neuronal damage. Our results recommend CuAB complex supplementation because it exerts neuroprotective effects against ND-induced toxicity.

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

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

Radioprotective potential of whey protein against gamma irradiation-induced lingual damage.

Introduction: Ionizing radiation (IR) is effectively used in the treatment of oral malignancies; however, it might also significantly harm the surrounding tissues. Whey protein isolate (WP) is a protein derived from milk that exhibits a wide range of bioactivities. Therefore, the present research aimed to delineate the mitigating impact of WP against gamma irradiation-induced lingual damage. Methods: Rats were randomized into 5 groups: Control (saline, orally, 14 days), WP (WP; 0.5 g/kg b. w., orally, 14 days), IR (saline, orally, 14 days, exposed to 6 and 3 Gy on days 4 and 6, respectively), WP+IR (WP was given orally for 14 days before and after IR exposure; exposed to 6 and 3 Gy on days 4 and 6, respectively), and IR+WP (WP, orally, started 24 h after 1st IR exposure till the end of the experiment) groups. Samples were collected at two-time intervals (on the 7th and 14th days). Results and Discussion: Oxidative stress was stimulated upon IR exposure in tongue, indicated by boosted malondialdehyde (MDA) level, along with a decrease in the total antioxidant capacity (TAC) level, superoxide dismutase (SOD), and catalase (CAT) activities. Additionally, IR exposure depicted an increase of serum IgE, inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, along with overexpression mRNA levels of nuclear factor kappa-B transcription factor/p65 (NF-κB/p65), and down-regulation of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase (HO-1) mRNA levels in tongue tissue. Moreover, IR triggered alterations in lingual histological architecture. The antioxidant and anti-inflammatory properties of WP mitigated oxidative damage, inflammation, and desquamation that were brought on following IR exposure. The protective administration of WP markedly decreases IR-induced lingual harm compared to the mitigation protocol. Our findings recommend WP supplements to the diets of cancer patients undergoing IR that might aid radioprotective effects.

Exploration of Tilmicosin Cardiotoxicity in Rats and the Protecting Role of the Rhodiola rosea Extract: Potential Roles of Cytokines, Antioxidant, Apoptotic, and Anti-Fibrotic Pathways.

Tilmicosin (TIL) is a common macrolide antibiotic in veterinary medicine. High doses of TIL can have adverse cardiovascular effects. This study examined the effects of Rhodiola rosea (RHO) that have anti-inflammatory, antioxidant, and anti-fibrotic effects on tilmicosin (TIL)-induced cardiac injury targeting anti-inflammatory, antioxidant, apoptotic, and anti-apoptotic signaling pathways with anti-fibrotic outcomes. Thirty-six male Wistar albino rats were randomly divided into groups of six rats each. Rats received saline as a negative control, CARV 1 mL orally (10 mg/kg BW), and RHO 1 mL orally at 400 mg/kg BW daily for 12 consecutive days. The TIL group once received a single subcutaneous injection (SC) dose of TIL (75 mg/kg BW) on the sixth day of the experiment to induce cardiac damage. The standard group (CARV + TIL) received CARV daily for 12 consecutive days with a single TIL SC injection 1 h after CARV administration only on the sixth day of study and continued for another six successive days on CARV. The protective group (RHO + TIL) received RHO daily for the same period as in CARV + TIL-treated rats and with the dosage mentioned before. Serum was extracted at the time of the rat's scarification at 13 days of study and examined for biochemical assessments in serum lactate dehydrogenase (LDH), cardiac troponin I (cTI), and creatine phosphokinase (CK-MB). Protein carbonyl (PC) contents, malondialdehyde (MDA), and total antioxidant capacity (TAC) in cardiac homogenate were used to measure these oxidative stress markers. Quantitative RT-PCR was used to express interferon-gamma (INF-γ), cyclooxygenase-2 (COX-2), OGG1, BAX, caspase-3, B-cell lymphoma-2 (Bcl-2), and superoxide dismutase (SOD) genes in cardiac tissues, which are correlated with inflammation, antioxidants, and apoptosis. Alpha-smooth muscle actin (α-SMA), calmodulin (CaMKII), and other genes associated with Ca2+ hemostasis and fibrosis were examined using IHC analysis in cardiac cells (myocardium). TIL administration significantly increased the examined cardiac markers, LDH, cTI, and CK-MB. TIL administration also increased ROS, PC, and MDA while decreasing antioxidant activities (TAC and SOD mRNA) in cardiac tissues. Serum inflammatory cytokines and genes of inflammatory markers, DNA damage (INF-γ, COX-2), and apoptotic genes (caspase-3 and BAX) were upregulated with downregulation of the anti-apoptotic gene Bcl-2 as well as the DNA repair OGG1 in cardiac tissues. Furthermore, CaMKII and α-SMA genes were upregulated at cellular levels using cardiac tissue IHC analysis. On the contrary, pretreatment with RHO and CARV alone significantly decreased the cardiac injury markers induced by TIL, inflammatory and anti-inflammatory cytokines, and tissue oxidative-antioxidant parameters. INF-γ, COX-2, OGG1, BAX, and caspase-3 mRNA were downregulated, as observed by real-time PCR, while SOD and Bcl-2 mRNA were upregulated. Furthermore, the CaMKII and α-SMA genes' immune reactivities were significantly decreased in the RHO-pretreated rats.

Arthrospira platensis Nanoparticles Mitigate Aging-Related Oxidative Injured Brain Induced by D-galactose in Rats Through Antioxidants, Anti-Inflammatory, and MAPK Pathways.

Background: Loss of normal function is an inevitable effect of aging. Several factors contribute to the aging process, including cellular senescence and oxidative stress. Methods: We investigate how Arthrospira platensis Nanoparticles (NSP) protect against aging injury induced by d-galactose (D-gal) in the rat. So, we subcutaneously (S/C) injected D-gal at 200 mg/kg BW to see if Arthrospira platensis Nanoparticles (NSP) might protect against the oxidative changes generated by D-gal. NSP (0.5 mg/kg body weight once daily by gastric gavage) was given to all groups apart from the control and D-gal groups. The d-gal + NSP group was supplemented with 200 mg of D-gal per kg BW once a day and NSP 0.5 mg/kg BW given orally for 45 days. Biochemical, mRNA expression, and histological investigations of brain tissues were used to evaluate the oxidative alterations caused by d-gal and the protective role of NSP. Results: Our data demonstrated that d-gal was causing significant reductions in relative brain and body weight with increased malondialdehyde (MDA) and redox oxygen species (ROS) levels and increases in serum creatine phosphokinase (CPK) and creatine phosphokinase isoenzyme BB (CPK-BB) with marked decreases in the level of antioxidant enzyme activity in the brain and acetylcholinesterase activity augmented with a phosphorylated H2A histone family member X (γ-H2AX) level increased. The D-gal group had considerably higher phosphorylated p38 mitogen-activated protein kinases (P38MAPK) and C-Jun N-terminal (JNK) kinases. The d-gal administration stimulates the apoptotic gene expression by downregulating the brain superoxide dismutase (SOD), catalase (CAT), and nuclear factor erythroid 2-related factor 2 (Nrf2). The NSP administration saved these parameters in the direction of the control. The brain histopathologic and immunohistochemistry analysis findings support our findings on NSP's protective role. Conclusion: The NSP may be a promising natural protective compound that can prevent aging and preserve health.

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

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

Lutein Modulates Oxidative Stress, Inflammatory and Apoptotic Biomarkers Related to Di-(2-Ethylhexyl) Phthalate (DEHP) Hepato-Nephrotoxicity in Male Rats: Role of Nuclear Factor Kappa B.

Phthalates are widely distributed in our environment due to their usage in many industries, especially in plastic production, which has become an essential part of daily life. This investigation aimed to assess the potential remedial influence of lutein, a naturally occurring carotenoid, on phthalate-triggered damage to the liver and kidneys. When di-(2-ethylhexyl) phthalate (DEHP) was administered to male albino rats over sixty straight days at a dosage of 200 mg/kg body weight, it resulted in a significant increase in the serum activity of liver enzymes (AST, ALT, and GGT), alpha-fetoprotein, creatinine, and cystatin-C, as well as disruptions in the serum protein profile. In addition, intoxication with DEHP affected hepato-renal tissues' redox balance. It increased the content of some proinflammatory cytokines, nuclear factor kappa B (Nf-κB), and apoptotic marker (caspase-3); likewise, DEHP-induced toxicity and decreased the level of anti-apoptotic protein (Bcl-2) in these tissues. Lutein administration at a dose level of 40 mg/kg b.w efficiently facilitated the changes in serum biochemical constituents, hepato-renal oxidative disturbance, and inflammatory, apoptotic, and histopathological alterations induced by DEHP intoxication. In conclusion, it can be presumed that lutein is protective as a natural carotenoid against DEHP toxicity.

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.

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

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

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.

Evaluating the ability of some natural phenolic acids to target the main protease and AAK1 in SARS COV-2.

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.

Promoter methylation might shift the balance of Galectin-3 & 12 expression in de novo adult acute myeloid leukemia patients.

Acute myeloid leukemia (AML) was reported as the most common type of leukemia among adults. Galectins constitute a family of galactose-binding proteins reported to play a critical role in many malignancies including AML. Galectin-3 and -12 are members of the mammalian galectin family. To understand the contribution of galectin-3 and -12 promoter methylation to their expression, we performed bisulfite methylation-specific (MSP)-PCR and bisulfite genomic sequencing (BGS) of primary leukemic cells in patients with de novo AML before receiving any therapy. Here, we show a significant loss of LGALS12 gene expression in association with promoter methylation. The lowest degree of expression was found in the methylated (M) group while the highest degree was in the unmethylated (U) group and the partially methylated (P) group expression lies in between. This was not the case with galectin-3 in our cohort unless the CpG sites analyzed were outside the frame of the studied fragment. We were also able to identify four CpG sites (CpG number 1, 5, 7& 8) in the promoter region of galectin-12; these sites must be unmethylated so that expression can be induced. As far as the authors know, these findings were not previously concluded in earlier studies.

Liver tissues oxidative status, epigenetic and molecular characteristics in rats administered magnetic and microwave treated water.

Physical and chemical changes in the natural of water may affect biological organisms. In this study, we highlight the effect of magnetized-water and microwave-water on rats' liver tissues. Three groups of albino rats were separated. The first, rats were administered tap-water. The second, rats were administered magnetized-water. The third, rats were administered microwave-water. After two months, the results revealed a significant increase in liver functioning enzymes' levels and bilirubin in rats administered microwave-water, compared to tap- and magnetic-water. In relation to oxidative stress, there was a significant increase and decrease in oxidative and antioxidant parameters respectively in liver tissues of rat's administrated microwave-water. At the molecular level, there was a significant down-regulation in Metallothionein, CYP genes in magnetic-water compared to tap-water. Rats administered microwave-water have shown a significant down-regulation in GST, Metallothionein and CYP genes' expression, however, Amylase and HDAC3 genes were significantly up-regulated, compared to the other groups. The intake of microwave-water resulted in notable histopathological changes in liver tissues. Rats administered magnetic-water showed no clear changes in their liver tissues. In summary, microwave-water induced stress and epigenetic effects compared with magnetic-water and tap-water. Also, magnetic-water produced from the higher magnetic power had no side effect on liver tissues.

Coenzyme Q10 enhances testicular functions and sexual behavior through regulating steroidogenic-related gene expression and inflammatory pathways of Japanese quail (Coturnix japonica) aganist cadmium.

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, 3ß-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.

Impending Chemotherapeutic Impact of Arthrospira platensis Nanoparticles and/or Sorafenib against Hepatocellular Carcinoma through Modulation of Antioxidant Status, Tumor Marker Genes, and Anti-Inflammatory Signaling Pathways.

This study investigated Arthrospira platensis 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 (n = 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 Arthrospira platensis 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-1ß) as well as the Ki-67 gene expression (p < 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 Preferential Therapeutic Potential of Chlorella vulgaris against Aflatoxin-Induced Hepatic Injury in Quail.

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 Chlorella vulgaris (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-1ß, 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.

Dietary Vitamin B Complex: Orchestration in Human Nutrition throughout Life with Sex Differences.

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.

The Potential Protective Effect and Underlying Mechanisms of Physiological Unconjugated Hyperbilirubinemia Mediated by UGT1A1 Antisense Oligonucleotide Therapy in a Mouse Model of Cyclosporine A-Induced Chronic Kidney Disease.

Cyclosporine A (CSA) is an immunosuppressive drug that has improved transplant survival rates. However, its use is often limited because it is thought to be linked to the development of chronic kidney disease after kidney transplants. This study aimed to investigate the protective effects and underlying mechanisms of physiological unconjugated (UC) hyperbilirubinemia mediated by UGT1A1 antisense oligonucleotide in a mouse model of CsA-induced chronic kidney disease, and match these with that of chitosan (CH) as a natural chelator against kidney injury. In the current study, CsA-treated mice were given an intravenous injection of UGT1A1 antisense morpholino oligonucleotide (16 µg/kg) every third day for 14 days. In serum samples, bilirubin, creatinine, and urea were determined. Markers of oxidative stress, antioxidant activities, and mRNA expression of target genes PPAR-α, cFn, eNOS, NF-B, AT1-R, ETA-R, Kim-1, and NGAL were measured in the kidney tissues. Moreover, histopathological examinations were carried out on the kidney tissue. Physiological UC hyperbilirubinemia could be a promising protective strategy against CsA-induced kidney disease in transplant recipients. UGT1A1 antisense oligonucleotide-induced physiological UC hyperbilirubinemia serum significantly protected against CsA-induced kidney dysfunction. UCB acts as a signaling molecule that protects against kidney disease through different mechanisms, including antioxidant, anti-inflammatory, and hormonal action, by activating nuclear hormone receptors (PPAR-α). Moreover, it significantly downregulated mRNA expression of NF-kB, ETA-R, iNOS, AT1-R, cFn, Kim-1, and NGAL in the kidney tissue and alleviated CsA-induced kidney histological changes in CsA-treated mice.

Ameliorative Impacts of Wheat Germ Oil against Ethanol-Induced Hepatic and Renal Dysfunction in Rats: Involvement of Anti-Inflammatory, Anti-Apoptotic, and Antioxidant Signaling Pathways.

Wheat germ oil (WGO) is a well-known product with anti-inflammatory and antioxidant properties. The current study aimed to investigate the impacts of WGO against ethanol-induced liver and kidney dysfunction at the serum, anti-inflammatory, antioxidants and anti-apoptotic signaling pathways. Rats received saline orally as a negative control or WGO in a dose of 1.5 mL/kg (1400 mg/kg body weight orally) for 15 days. The affected group received ethanol 50% v/v 10 mL/kg (5 g/kg) body weight orally once a day for consecutive 15 days to induce hepatorenal injuries in ethanolic non-treated group. The protective group received WGO daily 1 h before ethanol administration. Serum (1.5 mL) from blood was extracted and examined for the changes in biochemical assessments in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), bilirubin, serum γ-glutamyl transpeptidase (GGT), total protein, serum albumin, butyrylcholinesterase (BChE), total cholesterol (TC), total triglyceride (TG), urea, creatinine, uric acid, potassium (K+), Beta-2 microglobulin (ß2M), malondialdehyde (MDA), catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) and aspartate aminotransferase (AST). Kidney and liver homogenate was used to measure MDA, GSH and catalase activities. Quantitative real time PCR (qRT-PCR) was used to express Nrf2 and HO-1 in liver, and NF-kB and kidney injury molecule (KIM-1) in kidneys, which are correlated with oxidative stress and inflammation. Capase-3 and Bcl2 genes were examined using immunohistochemical analysis in the kidney and liver. Ethanol administration induced significant alteration in examined liver and kidney markers (AST, ALT, GGT, ALP, total proteins, urea, creatinine and uric acid). Moreover, alcohol administration decreased antioxidant activities at serum and hepatorenal tissues (GSH, catalase and SOD), while MDA was increased as a tissue degradation marker. Inflammatory cytokines, together with genes of oxidative stress markers (Nrf2 and HO-1), were all affected. At cellular levels, apoptotic marker caspase-3 was upregulated, while antiapoptotic marker B-cell lymphoma 2 (Bcl2), was down regulated using immunohistochemical analysis. Of interest, pretreatment with WGO improved the side effects induced by ethanol on hepatic, renal biomarkers and reversed its impact on serum and tissue antioxidant parameters. Nrf2/HO-1 were upregulated, while NFk-B and KIM-1 were downregulated using real time PCR. Immune reactivities of caspase-3 and Bcl2 genes were restored in the protective group. In conclusion, WGO ameliorated ethanol-induced hepatic and renal dysfunction at the biochemical, molecular and cellular levels by regulating some mechanisms that controls oxidative stress, apoptosis, inflammation and anti-apoptotic pathways.

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.