Impact of dietary-nucleotides and Saccharomyces cerevisiae-derivatives on growth-performance, antioxidant-capacity, immune-response, small-intestine histomorphometry, caecal-Clostridia, and litter-hygiene of broiler-chickens treated with florfenicol.

Stress in poultry production is energy-demanding. Nucleotides and yeast cell-wall products are essential nutrients for broiler performance, gut function, and immune response. Antibiotics, like florfenicol, negatively affect the immune system. A total of 600 one-d-old broiler chickens (Cobb-500) were weighed and randomly allotted into four groups with three replicates each. The control group (G1) received the basal diet, G2 received a diet supplemented with a combination of nucleotides and Saccharomyces cerevisiae derivatives (250 g/Ton), G3 received the basal diet and medicated with florfenicol (25 mg/Kg body weight) in drinking water for 5 days, while G4 received a combination of nucleotides and Saccharomyces cerevisiae-derivatives (250 g/Ton) and medicated with florfenicol in drinking water. Growth performance criteria were recorded weekly. Blood, intestinal contents, small-intestine sections, and litter samples were collected to measure birds' performance, carcass yields, leukocytic counts, antioxidant capacity, antibody titres, phagocytic index, caecal Clostridia, intestinal histomorphometry, and litter hygiene. Nucleotide-supplemented groups (G2 and G4) revealed significant (p ≤ 0.05) improvements in feed conversion, and body weight, but not for carcass yields in comparison to the control. Dietary nucleotides in G2 elevated blood total proteins, leucocytic count, antioxidant capacity, and phagocytic index, while they lowered blood lipids and litter moisture and nitrogen (p ≤ 0.05). Dietary nucleotides in G4 ameliorated the immunosuppressive effect of florfenicol (p ≤ 0.05) indicated in reducing caecal Clostridia, improving duodenal and ileal villi length, and increasing blood albumin and globulin levels, and phagocytosis%. Supplementing diets with nucleotides and yeast products has improved the immune system and provided a healthier gut for broilers.

Ameliorative effects of rutin and rutin-loaded chitosan nanoparticles on testicular oxidative stress and histological damage induced by cyclophosphamide in male rats.

Cyclophosphamide (CP) is broadly used to kill various tumor cells; however, its repeated uses have been reported to cause reproductive dysfunction and infertility. Natural flavonoid, rutin (RUT), possesses strong antioxidant and antiapoptotic activity that is attributed to ameliorate the reproductive dysfunction induced by CP. Many previous studies proved that the formulation of flavonoids in nanoemulsion has a promising perspective in mitigating the side effects of chemotherapy. Therefore, the main objective of this study was to investigate the ameliorative effects of RUT and RUT-loaded chitosan nanoparticles (RUT-CH NPs) against CP-induced reproductive dysfunction in male rats. For this aim, thirty-six male albino rats were randomly allocated into six groups as follows: control, RUT, RUT-CH NPs, CP, CP + RUT, and CP + RUT-CH NPs. In the CP groups, a single intraperitoneal injection of CP (150 mg/kg bwt) was administered on the first day of the experiment. RUT and RUT-CH NPs were orally administered either alone or with CP injection at a dose of 10 mg/kg bwt per day for 60 days. The results revealed that CP administration caused significant testicular oxidative stress damage through increasing the nitric oxide and malondialdehyde levels as well as decreasing the total antioxidant capacity and reduced glutathione contents. It also impaired spermatogenesis and steroidogenesis via altering the transcription levels of CYP11A1, HSD-3b, StAR, Bax, bcl-2, and Nrf-2 genes. Otherwise, the oral intake of either RUT or RUT-CH NPs with CP injection effectively attenuated these alterations and significantly improved the microscopic appearance of testicular tissue. In conclusion, this study highlights the potential of RUT either free or NPs in mitigating CP-induced testicular dysfunction via its antioxidant and anti-apoptotic properties.

Neuroprotective effect of quercetin and nano-quercetin against cyclophosphamide-induced oxidative stress in the rat brain: Role of Nrf2/ HO-1/Keap-1 signaling pathway.

Quercetin (Qu) is a powerful flavanol antioxidant that is naturally found in plants and is part of the flavonoid family. Qu has a wide range of biological properties, such as neuroprotective, anti-cancer, anti-diabetic, anti-inflammatory, and radical scavenging capabilities. However, the in vivo application of Qu is limited by its poor water solubility and low bioavailability. These issues could be addressed by utilizing Qu nanoformulations. Cyclophosphamide (CP) is a potent chemotherapeutic agent that causes severe neuronal damage and cognitive impairment due to reactive oxygen species (ROS) overproduction. The present study aimed to explore the proposed neuroprotective mechanism of quercetin (Qu) and quercetin-loaded Chitosan nanoparticles (Qu-Ch NPs) against the brain oxidative damage induced by CP in male albino rats. For this aim, thirty-six adult male rats were randomly divided into six groups (n = 6). Rats were pretreated with Qu and Qu-Ch NPs orally in doses of 10 mg/kg bwt/day for 2 weeks, and CP (75 mg/kg bwt) was administered intraperitoneally 24 h before the termination of the experiment. After 2 weeks, some neurobehavioral parameters were evaluated, and then euthanization was done to collect the brain and blood samples. Results showed that CP induces neurobehavioral deteriorations and impaired brain neurochemical status demonstrated by a significant decrease in brain glutathione (GSH), serum total antioxidant capacity (TAC), and serotonin (5-HT) levels while malondialdehyde (MDA), nitric oxide (NO), Tumor necrosis factor α (TNFα), and choline esterase (ChE) concentrations increased significantly compared to the control group. Pretreatment with Qu and Qu-Ch NPs showed a significant anti-oxidative, anti-depressive, and neuroprotective effect through modification of the above-mentioned parameters. The results were further validated by assessing the expression levels of selected genes in brain homogenates and histopathological investigations were done to pinpoint the exact brain-altered regions. It could be concluded that Qu and Qu-Ch NPs can be useful neuroprotective adjunct therapy to overcome neurochemical damage induced by CP.

Potential Mechanisms of Imidacloprid-Induced Neurotoxicity in Adult Rats with Attempts on Protection Using Origanum majorana L. Oil/Extract: In Vivo and In Silico Studies.

Imidacloprid (IMI) insecticide is rapidly metabolized in mammals and contributes to neurotoxicity via the blocking of nicotinic acetylcholine receptors, as in insects. Origanum majorana retains its great antioxidant potential in both fresh and dry forms. No data is available on the neuroprotective effect of this plant in laboratory animals. In this context, aerial parts of O. majorana were used to prepare the essential oil (OMO) and methanol extract (OME). The potential neuroprotective impact of both OMO and OME against IMI-induced neurotoxicity in rats was explored. Forty-two rats were divided into 6 groups, with 7 rats in each one. Rats were daily administered the oral treatments: normal saline, OMO, OME, IMI, IMI + OMO, and IMI + OME. Our results revealed the identification of 55 components in O. majorana essential oil, most belonging to the oxygenated and hydrocarbon monoterpenoid group. Moreover, 37 constituents were identified in the methanol extract, mostly phenolics. The potent neurotoxic effect of IMI on rats was confirmed by neurobehavioral and neuropathological alterations and a reduction of both acetylcholine esterase (AchE) activity and dopamine (DA), serotonin (5HT), and γ-aminobutyric acid (GABA) levels in the brain. Exposure of rats to IMI elevates the malondialdehyde (MDA) levels and reduces the antioxidant capacity. IMI could upregulate the transcription levels of nuclear factor-κB (NF-κB), interleukin-1 ß (IL-1ß), and tumor necrosis factor (TNF-α) genes and express strong caspase-3 and inducible nitric oxide synthase (iNOS) immunostaining in most examined brain areas. On the other hand, rats coadministered OMO or OME with IMI showed a marked improvement in all of the studied toxicological parameters. In conclusion, cotreatment of O. majorana extracts with IMI can protect against IMI neurotoxicity via their potent antioxidant, anti-inflammatory, and anti-apoptotic effects. Thus, we recommend a daily intake of O. majorana to protect against insecticide's oxidative stress-mediated neuroinflammatory stress and apoptosis. The molecular docking study of linalool, rosmarinic acid, γ-terpene, and terpene-4-ol justify the observed normalization of the elevated iNOS and TNF-α levels induced after exposure to IMI.

The potential mechanism underlying the hepatorenal toxicity induced by hymexazol in rats and the role of NF-κB signaling pathway.

Hymexazol (HML) is widely used in agriculture as a systemic fungicide and plant growth promoter. Humans are continuously exposed to HML via various routes. The liver and kidneys are essential organs for the detoxification, metabolism, and excretion of HML. However, data concerning the impact of HML on nontarget organisms are scarce. The present study aimed to determine the mechanism of dose-dependent hepatorenal toxicity of HML in rats. Twenty-one rats were divided into three equal groups that received the following treatments via oral intake daily for 14 days: group 1, normal saline; group 2, low dose of HML (1/80 LD50 ); group 3, high dose of HML (1/40 LD50 ). We weighed the rats at the beginning and the end of the experiment to record the weight gain in each group. The results showed that HML induced dose-dependent hepatorenal toxicity manifested by a significant increase in malondialdehyde levels, a decrease in total antioxidant capacity and reduced glutathione contents, and upregulation of the transcriptase levels of the nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1ß) genes. The HML-exposed groups displayed various histopathological changes in both organs, with significant elevation of all serum liver and kidney biomarkers. In conclusion, HML produced hepatorenal toxicity in rats through oxidative stress that mediates the NF-κB signaling pathway in response to pro-inflammatory cytokines such as TNF-α and IL-1ß. We advise limiting the use of HML in agricultural and veterinary practices and finding an alternative agent to avoid the human and animal health risks induced by HML exposure.

Origanum majorana essential oil improves the rat's sexual behavior and testicular oxidative damage induced by imidacloprid via modulating the steroidogenesis pathways.

The neonicotinoid insecticide imidacloprid has been linked to significant reproductive damage in mammals. Origanum majorana essential oil (OME) is a natural herbal product used in the management of many diseases due to its strong antioxidant effects. The oil was hydrodistilled from O. Majorana and analyzed using GC/MS then its possible protective mechanisms against IMI-induced reprotoxicity in male rats were investigated. 28-adult male Wistar rats were divided into 4 groups as follows: group (1) control group, group (2) OME, group (3) IMI, and group (4) IMI + OME. The treatments were applied daily via oral gavage for 60 days. Remarkable abnormalities in both territorial aggressive and sexual behaviors were observed in IMI-treated rats with a significant elevation of serum FSH and LH as well as altered testicular redox status. Along with inhibition of the testicular expression of StAR and aromatase genes and serum total testosterone in addition to abnormal sperm count, viability, motility, and morphology. Histopathological examination showed severe degeneration and necrosis in both germ cells and Leydig cells with atrophy in most of the seminiferous tubules. Co-administration of OME with IMI notably improved all the above-mentioned studied parameters, and restored rats' spermatogenesis, sexual behavior, and favorably modulates the levels of both testosterone and gonadotropic hormones via its potent antioxidant effect. These findings support the use of OME as a fertility enhancer and suggest that it could be used to manage pesticide-induced male infertility.

A Comprehensive Study on the Mechanistic Way of Hexaflumuron and Hymexazol Induced Neurobehavioral Toxicity in Rats.

Pesticides are widely used in agriculture to kill pests, but their action is non-selective and results in several hazardous effects on humans and animals. Pesticide toxicity has been demonstrated to alter a variety of neurological functions and predisposes to various neurodegenerative diseases. Although, there is no data available for hexaflumuron (HFM) and hymexazol (HML) neurotoxicity. Hence, the present study aims to investigate the possible mechanisms of HFM and HML neurotoxicity. 21 male Wistar rats were divided into three groups and daily received the treatment via oral gavage for 14 days as follows: group (1) normal saline, group (2) HFM (1/100LD50), and group (3) HML (1/100 LD50). Our results revealed that both HFM and HML produced a significant increase in MDA levels and a decrease in GSH and CAT activity in some brain areas. There were severe histopathological alterations mainly neuronal necrosis and gliosis in different examined areas. Upregulation of mRNA levels of JNK and Bax with downregulation of Bcl-2 was also recorded in both pesticides exposed groups. In all studied toxicological parameters, HML produced neurotoxicity more than HFM. HFM targets the cerebral cortex and striatum, while HML targets the cerebral cortex, striatum, hippocampus, and cerebellum. We can conclude that both HFM and HML provoke neurobehavioral toxicity through oxidative stress that impairs the mitochondrial function and activates the JNK-dependent apoptosis pathway.

Novel insights into the potential mechanisms underlying carbendazim-induced hepatorenal toxicity in rats.

Carbendazim (CBZ) is a common environmental pollutant that can contaminate food and water and severely damage human health. Some studies revealed the adverse effect of CBZ on different organs, but its detailed toxicity mechanism has not been elucidated yet. Thus, the present study aims to clarify the mechanisms of CBZ-induced hepatorenal toxicity in rats. Therefore, we partitioned 40 male Wistar rats into four groups (n = 10): a negative control group and three treatment groups, which received 100, 300, and 600 mg/kg of CBZ. All rats received the treatment daily by oral gavage. We collected blood and organ samples (liver and kidney) at 14 and 28 days postdosing. CBZ caused extensive pathological alterations in both the liver and kidneys, such as cellular degeneration and necrosis accompanied by severe inflammatory reactions in a dose- and time-dependent manner. All the CBZ-treated groups displayed strong tumor necrosis factor-α and nuclear factor-κB (NF-κB) immunopositivity. Additionally, CBZ dose-dependently elevated the alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea, and creatinine serum levels and reduced the serum albumin levels. Furthermore, CBZ-induced apoptosis, as indicated by the observed Bax gene upregulation and Bcl-2 gene downregulation in both organs. All these changes may be related to oxidative stress, as indicated by the increase in malondialdehyde levels and the decrease in total antioxidant capacity. Our results demonstrate that CBZ-induced dose- and time-dependent hepatorenal damage through oxidative stress, which activated both the NF-κB signaling pathway and Bcl-based programmed cell death.

Comparative assessment on the probable mechanisms underlying the hepatorenal toxicity of commercial imidacloprid and hexaflumuron formulations in rats.

Pesticides are viewed as a major wellspring of ecological contamination and causing serious risky consequences for people and animals. Imidacloprid (IM) and hexaflumuron (HFM) are extensively utilized insect poisons for crop assurance on the planet. A few investigations examined IM harmfulness in rodents, but its exact mechanism hasn't been mentioned previously as well as the toxicity of HFM doesn't elucidate yet. For this reason, the present study was designed to explore the mechanism of each IM and HFM-evoked rat liver and kidney toxicity and to understand its molecular mechanism. 21 male Wistar albino rats were divided into 3 groups, as follows: group (1), normal saline; group (2), IM; and group (3), HFM. Both insecticides were orally administered every day for 28 days at a dose equal to 1/10 LD50 from the active ingredient. After 28 days postdosing, rats were anesthetized to collect blood samples then euthanized to collect liver and kidney tissue specimens. The results showed marked changes in walking, body tension, alertness, and head movement with a significant reduction in rats' body weight in both IM and HFM receiving groups. Significant increases in MDA levels and decrease of GHS levels were recorded in liver and kidney homogenates of either IM or HFM groups. Liver and kidney tissues obtained from both pesticide receiving groups showed extensive histopathological alterations with a significant increase in the serum levels of ALT, AST, urea, and creatinine and a decrease in total proteins, albumin, and globulin levels. In addition, there was upregulation of the transcript levels of casp-3, JNK, and HO-1 genes with strong immunopositivity of casp-3, TNF-á½°, and NF-KB protein expressions in the liver and kidneys of rats receiving either IM or HFM compared with the control group. In all studied parameters, HFM caused hepatorenal toxicity more than those induced by IM. We can conclude that each IM and HFM provoked liver and kidneys damage through overproduction of ROS, activation of NF-KB signaling pathways and mitochondrial/JNK-dependent apoptosis pathway.