Physiological roles of propolis and red ginseng nanoplatforms in alleviating dexamethasone-induced male reproductive challenges in a rat model.

BACKGROUND: Red ginseng and propolis are well-known antioxidants that have been related to a reduction in oxidative stress. OBJECTIVE: This study evaluated the efficiency of red ginseng and propolis, either in powder or as nano-forms against dexamethasone-induced testicular oxidative challenges in adult male albino rats. METHODS: Forty rats were divided into 8 equal groups including control negative group that was given vehicle (DMSO), control positive group that was administered dexamethasone in addition to the nano-propolis, nano-ginseng, nano-propolis + dexamethasone, nano ginseng+dexamethasone, propolis+dexamethasone and ginseng + dexamethasone groups. Serum, semen and tissue samples were obtained. RESULTS: Lower testosterone levels, higher levels of MDA, and lower levels of total antioxidant capacity in serum, as well as impaired semen quality and a disturbed histopathological picture of both the testis and seminal glands, were all observed as significant negative effects of dexamethasone. These findings were confirmed by lower gene expression profiles of CYP11A1, StAR, HSD-3b, Nrf-2 and ACTB-3b in testicular and seminal gland tissues. The most powerful anti-dexamethasone effects were obtained with either propolis in nanoform or conventional ginseng. CONCLUSION: Propolis nano-formulation and ginseng in conventional form could be considered excellent candidates to ameliorate the oxidative stress provoked by dexamethasone, however, neither nano-ginseng nor conventional propolis showed such effects.

Modified Citrus Pectin (MCP) Confers a Renoprotective Effect on Early-Stage Nephropathy in Type-2 Diabetic Mice.

Diabetic nephropathy (DN) is a significant global health concern with a high morbidity rate. Accumulating evidence reveals that Galectin-3 (Gal-3), a ß-galactoside-binding lectin, is a biomarker in kidney diseases. Our study aimed to assess the advantageous impacts of modified citrus pectin (MCP) as an alternative therapeutic strategy for the initial and ongoing progression of DN in mice with type 2 diabetes mellitus (T2DM). The animal model has been split into four groups: control group, T2DM group (mice received intraperitoneal injections of nicotinamide (NA) and streptozotocin (STZ), T2DM+MCP group (mice received 100 mg/kg/day MCP following T2DM induction), and MCP group (mice received 100 mg/kg/day). After 4 weeks, kidney weight, blood glucose level, serum kidney function tests, histopathological structure alterations, oxidative stress, inflammation, apoptosis, and fibrosis parameters were determined in renal tissues. Our findings demonstrated that MCP treatment reduced blood glucose levels, renal histological damage, and restored kidney weight and kidney function tests. Additionally, MCP reduced malondialdehyde level and restored glutathione level, and catalase activity. MCP demonstrated a notable reduction in inflammatory and apoptosis mediators TNF-α, iNOS, TGF-ßRII and caspase-3. Overall, MCP could alleviate renal injury in an experimental model of DN by suppressing renal oxidative stress, inflammation, fibrosis, and apoptosis mediators.

Effect of Spirulina platensis on growth, hematological, biochemical, and immunological parameters of Nile tilapia (Oreochromis niloticus).

This study was conducted to evaluate the effects of Spirulina platensis in Nile tilapia diets on growth performance, blood hematological and biochemical parameters, immunological status, and intestinal histomorphometry. A total of 228 fish were randomly allocated into four groups with triplicates (19 fish per replicate). The first group was fed the control diet, which contained no Spirulina supplementation. The other three groups were fed diets containing graded levels of powdered Spirulina: 2.5%, 5.0%, and 10.0% in the second, third, and fourth group, respectively. S. platensis was added to the diets partially substituting the fish meal content. The experiment lasted for 8 weeks. The results showed that dietary Spirulina supplementation improved (P < 0.05) the body weight and length, weight gain, specific growth rate, condition factor, and feed conversion efficiency. Moreover, Spirulina increased significantly (P < 0.05) the hemoglobin, PCV, RBCs, and WBCs count. Also, it increased the lymphocytes, eosinophils, IgM level, lysozyme activity, and phagocytic activity in the blood. Additionally, the Spirulina raised (P < 0.05) the serum albumin level but reduced (P < 0.05) the creatinine and urea levels. The addition of Spirulina increased (P < 0.05) the height and width of intestinal villi and the lymphocytes and goblet cells count in the intestine. The obtained results were increased by increasing the inclusion level of Spirulina, especially for body weight and length, weight gain, FCR, phagocytic activity, and intestinal parameters. In conclusion, supplementing S. platensis can improve the growth performance of fish. Moreover, it can stimulate the immunity of fish through increasing the level of immunological blood indicators (IgM, lysozyme, phagocytic activity, lymphocytes, and eosinophils) as well as the local intestinal immunity (lymphocytes and goblet cells). So, it can be recommended to use S. platensis in fish diets not only to improve the growth performance but also to enhance the immune status.

Effects of dietary boron supplementation on the testicular function and thyroid activity in male goats: Involvement of CYP17A1 gene.

The physiological effects of dietary boron (B) supplementation for farm animals specifically goat on male fertility are still scarce and need deep investigation. Thus, the current study was designed to investigate how adding B to the diet of male goats affected their testicular and thyroid activity. For that purpose, twelve male goats were divided randomly into two groups (six animals each); control group that was fed the basal diet and B group that was fed the basal diet containing 70 mg B/kg diet for 6 months. Serum samples were collected at different intervals, while testicular biopsies were obtained at the end of the experiment. The results showed that 6 months of dietary B supplementation resulted in a significant increment in serum B concentration. The results of repeated measure analysis showed that there were significant GROUP and TIME × GROUP interactions effects on blood testosterone levels (F = 119.408, p = .000 and F = 6.794, p = .013, respectively), demonstrating that compared with control, B supplementation caused a significant rise in serum testosterone levels over time. However, the mean animal body weights and the serum levels of triiodothyronine (T3) and thyroxine (T4) were kept comparable with the control ones at the different time points. The most striking finding is that B supplementation increased significantly the mRNA expression of the CYP17A1 which is essential for steroidogenesis (p < .001). In addition, a histological examination of testicular tissue corroborated our findings and demonstrated that B supplementation had a positive effect. As a result, B might be considered an excellent food supplement that could be safely added to the male goats' diet at the current dose to improve their reproductive capacity.

Impact of humate substances and Bacillus subtilis PB6 on thyroid activity and histomorphometry, iron profile and blood haematology of quail.

The purpose of this study was to assess the effects of dietary humate substances (HS) and CloSTAT (Bacillus subtilis PB6) on the thyroid activity and histology, iron profile, blood haematology and performance of growing Japanese quail. A total of 216 unsexed 7-day-old quail chicks were randomly assigned to six groups. The first group was fed a basal diet (BD) without any additives (control); the 2nd group received BD plus 0.05% CloSTAT, the 3rd and 4th groups were given BD plus 0.4% and 0.8% HS, respectively; and the 5th and 6th groups were administered BD plus CloSTAT + 0.4% HS and BD plus CloSTAT + 0.8% HS, respectively. The results showed that the growth performance was improved with the addition of CloSTAT alone or in combination with 0.4% HS compared with the control. Haematological parameters, iron level and transferrin saturation % were significantly (p < 0.001) increased by feeding HS compared with the control group. Serum thyroxin and triiodothyronine levels were significantly (p = 0.001) increased by adding CloSTAT relative to the control. Supplementation of 0.8% HS caused deterioration in histomorphometry parameters of the thyroid gland, but these parameters were improved in response to CloSTAT compared with the control. In conclusion, dietary B. subtilis PB6 as CloSTAT or CloSTAT + 0.4% HS supplementation may be efficacious in enhancing the growth performance and boosting the thyroid activity of growing Japanese quail. Moreover, the addition of 0.4% or 0.8% HS to quail diets boosted their iron profile and haematological parameters.

Effect of dietary protease supplementation on growth performance, water quality, blood parameters and intestinal morphology of Nile tilapia (Oreochromis niloticus).

This study was conducted to evaluate the effect of using protease in diets of Nile tilapia on growth performance, water quality, blood parameters and intestinal morphology. The cost of these diets and their return on fish performance was calculated. A total of 360 fish were randomly allocated into four groups with triplicates (30 fish per replicate). Four diets were formulated; two controls (without protease supplementation) and two experimental diets (supplemented with protease). The first control diet contained the normal protein requirement (30% CP; control +ve), while the second control had a low protein content (29% CP; control -ve). The third diet was supplemented with protease at a dose of 500 g/ton, and its CP content was reduced to 29.0%, by reducing the fish meal content. The fourth diet contained the same CP level as the first control (30%) and supplemented with 250 g protease per ton feed. The experiment lasted for 14 weeks. The results showed that body weight and length, weight gain, specific growth rate, feed intake and feed conversion efficiency in the control -ve group (low CP) supplemented with protease were similar (p > 0.05) to that of the control +ve with normal CP content. However, these performance parameters were lower (p < 0.05) in fish fed low CP diet without protease supplementation. Providing protease to the control +ve diet improved all measured performance indices. The ammonia and nitrite concentrations of the water were reduced (p < 0.05) in control -ve and protease-supplemented groups. The height and width of intestinal villi were increased (p < 0.05) in fish fed diets containing protease. The inclusion of protease reduced the diet cost and also the feed cost of fish weight gain. In conclusion, supplementation of protease can improve the productive performance of fish, spare dietary protein and produce economical diets. Moreover, it can help in improving the water quality of fish via lowering the ammonia and nitrite contents, or through increasing the degradation of dietary protein.

Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin.

Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions.

Correction to: Oral inoculation of ultraviolet-irradiated Eimeria species oocysts protects chickens against coccidiosis.

The author name Salama Abohamra in the original published version of this article should have been Salama Abohamra Sayed Shany.

Oral inoculation of ultraviolet-irradiated Eimeria species oocysts protects chickens against coccidiosis.

Prevention of coccidiosis is one of the best ways of controlling disease. Therefore, the present study was carried out to evaluate the protective effect of ultraviolet (UV)-irradiated sporulated oocysts of Eimeria species against coccidiosis in layer chickens. One hundred forty-four one-day-old layer chicks were randomly divided into 4 groups (n = 36), including non-immunized/non-challenged negative control group (NC group), non-immunized/challenged control group (NIC group), non-irradiated sporulated oocyst/challenged group (CA group), and UV-irradiated sporulated oocyst/challenged (UV group). At the age of 4 days, chickens in groups UV and CA were both orally inoculated with 1.0 × 104 UV-irradiated and non-irradiated sporulated oocysts of Eimeria species, respectively. Chickens in groups NIC and NC were served as positive and negative controls, respectively. Chickens in all groups were orally challenged with 7.5 × 104 sporulated oocysts of Eimeria species except the NC group at the age of 21 days. The results revealed that chicks receiving UV-irradiated sporulated oocysts had no signs of illness with minimal or no changes in the cecal integrity and a significantly lower oocyst shedding (OPG) than in the NIC group. Additionally, the cytokine gene expression profiles were evaluated. Expression levels of IL-2, IL-12, and IFN-γ were significantly higher in the spleen of chicks in the UV and CA groups than in the NC group post-challenge. As expected, treatment with irradiated oocysts resulted in a significant reduction in oocyst shedding and maintenance of cecal mucosal integrity. Furthermore, the body weight was higher in chickens inoculated with UV-irradiated oocysts than their non-irradiated counterparts. In conclusion, our results demonstrate that inoculation with UV-irradiated sporulated oocysts of Eimeria species can produce a substantial reduction in infection symptoms.

Immunopathological assessments of human Blastocystis spp. in experimentally infected immunocompetent and immunosuppresed mice.

Blastocystis spp., one of the most common parasites colonizing the human intestine, is an extracellular, luminal protozoan with controversial pathogenesis. The host's immune response against Blastocystis spp. infection has also not been defined yet. Therefore, this research aimed to assess the potential pathogenicity of this parasite and its ability to modulate the immune response in experimental infected immunocompetent and immunosuppresed mice. These results demonstrated that the infected immunosuppressed mice were more affected than infected immunocompetent mice. Histopathological examination of the small intestine in the infected immunosuppressed mice showed that Blastocystis spp. infiltrated all the layers. Moreover, the epithelia showed exfoliation and inflammatory cell infiltration in submucosa compared to that of the infected immunocompetent mice. As well, examination of the large intestine of the infected immunosuppressed group showed severe goblet cell hyperplasia. Blastocystis spp. infiltrated all the large intestine layers compared to that of the infected immunocompetent group. Furthermore, there was a significant upregulation of the expression of proinflammatory cytokines: interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF-α) in the infected immunosuppressed mice compared to that of the infected immunocompetent ones (p ≤ 0.004 and p ≤ 0.002, respectively). However, the expression of anti-inflammatory cytokines (IL-4 and IL-10) was significantly downregulated in the infected immunosuppressed group compared to that of the infected immunocompetent group one at 10 days postinfection (p ≤ 0.002 and p ≤ 0.001, respectively). The results of this study revealed that Blastocystis spp. affected the production of pro- and anti-inflammatory cytokines in both groups of mice compared to healthy normal (naive) group. Additionally, these data showed that there was a significant upregulation (p ≤ 0.005) of the locally synthesized antibody: secretary IgA (sIgA) in the gut of the infected immunocompetent mice when compared to that of the infected immunosuppressed ones.

Zinc Oxide Nanoparticles and Vitamin C Ameliorate Atrazine-Induced Hepatic Apoptosis in Rat via CYP450s/ROS Pathway and Immunomodulation.

Atrazine, as an herbicide, is used widely worldwide. Because of its prolonged persistence in the environment and accumulation in the body, atrazine exposure is a potential threat to human health. The present study evaluated the possible protective effects of zinc oxide nanoparticles and vitamin C against atrazine-induced hepatotoxicity in rats. Atrazine administered to rats orally at a dose of 300 mg/kg for 21 days caused liver oxidative stress as it increased malondialdehyde (MDA) formation and decreased reduced glutathione (GSH) contents. Atrazine induced inflammation accompanied by apoptosis via upregulation of hepatic gene expression levels of NF-κB, TNF-α, BAX, and caspase-3 and downregulation of Bcl-2 gene expression levels. Additionally, it disturbed the metabolic activities of cytochrome P450 as it downregulated hepatic gene expression levels of CYP1A1, CYP1B1, CYP2E1. The liver function biomarkers were greatly affected upon atrazine administration, and the serum levels of AST and ALT were significantly increased, while BWG%, albumin, globulins, and total proteins levels were markedly decreased. As a result of the above-mentioned influences of atrazine, histopathological changes in liver tissue were recorded in our findings. The administration of zinc oxide nanoparticles or vitamin C orally at a dose of 10 mg/kg and 200 mg/kg, respectively, for 30 days prior and along with atrazine, could significantly ameliorate the oxidative stress, inflammation, and apoptosis induced by atrazine and regulated the hepatic cytochrome P450 activities. Furthermore, they improved liver function biomarkers and histopathology. In conclusion, our results revealed that zinc oxide nanoparticles and vitamin C supplementations could effectively protect against atrazine-induced hepatotoxicity.

Repro-protective activity of amygdalin and spirulina platensis in niosomes and conventional forms against aluminum chloride-induced testicular challenge in adult rats: role of CYP11A1, StAR, and HSD-3B expressions.

The male reproductive system is negatively influenced by Al exposure. Al represented a considerable hazard to men's reproduction capabilities. Amygdalin (AMG) and spirulina platensis (SP) have been considered to have a strong antioxidant and repro-protective activity; also, targeted drug delivery systems called niosomes improve the distribution of water-soluble medications like amygdalin and spirulina. Current study targeted to determine the effectiveness of AMG and SP against negative reproductive impact resulted by aluminum chloride (AlCl3) toxicity. Sixty adult male albino rats were separated into 6 groups, including the control group, which received distilled water; AlCl3 group, which received AlCl3; AMG+AlCl3 group, which received AlCl3+AMG; AMGLN+AlCl3 group, which received AlCl3+amygdalin-loaded niosomes; SP+AlCl3 group, which received AlCl3+SP; and SPLN+AlCl3 group, which received AlCl3+spirulina-loaded niosomes. All treatments were orally gavaged daily for 5 weeks, and rats were weighed weekly. At the termination of the experiment, some males (three from each group) were used for fertility traits via mating thirty virgin rat females (in a ratio of 1:2 and 2:3 male:female, respectively) followed by recording of birth weights and litter size (number of pups per each female) at birth to assess males' reproductive capability. Other males were euthanized for collection of serum, epididymal semen samples, and tissue samples for biochemical, sperm evaluation, gene expression, and histopathological measurements. There are a considerable number of negative impacts of AlCl3 on male fertility clarified by declined serum testosterone levels; an increased oxidative stress (MDA, TAC); deteriorated semen quality; down-regulation of CYP11A1, StAR, and HSD-3b gene expressions; and testicular tissue degenerative changes. In addition, litter size (number of pups per each female) and birth weights of pups obtained from mated females were affected. AMG and SP treatments, either in niosomal or conventional form, alleviated the AlCl3 negative effects by reducing oxidative stress; increasing testosterone levels; improving semen quality; upregulating of CYP11A1, StAR, and HSD-3b gene expressions; and reducing degenerative changes of testicular tissue. Besides, negative reproductive effect was diminished as observed by changes in the litter size (number of pups per each female) and birth weights of pups obtained from mated females. AMG and SP treatments (either in niosomal or conventional form), ameliorated the AlCl3 negative effects as they possess powerful antioxidant activity, as well as they have the ability to improve the reproductive activity of affected males.

Nephroprotective potential of eugenol in a rat experimental model of chronic kidney injury; targeting NOX, TGF-ß, and Akt signaling.

Chronic kidney disease is a crucial health problem associated with high morbidity and mortality. Eugenol is a natural phenolic plant compound with various pharmacological activities including antioxidant and anti-inflammatory properties. This study was designed to evaluate the possible protective effect of different eugenol doses in an experimental model of chronic CCl4-induced renal damage and investigate various mechanisms that underlie this postulated effect. Eugenol treatment (100 mg/kg) ameliorated kidney damage induced by CCl4 and rectified the distorted kidney function parameters and renal histological structure. Additionally, eugenol at a dose of 100 mg/kg suppressed the upregulated oxidative stress, inflammation and apoptosis in CCl4-treated rats as evident by down regulations of NADPH oxidase (NOX2 and NOX4), proinflammatory markers (IL-6 and TNF-α) and proapoptotic markers (cyt c and caspase-3), respectively. Importantly, eugenol co-administration in rats challenged with CCl4 downregulated the renal protein expressions of both TGF-ß as well as pAkt compared with CCl4 group. In conclusion, eugenol showed a potent nephroprotective effect against CCl4-induced renal damage through its antioxidant, anti-inflammatory and anti-fibrotic activities.

Developmental Programming: Physiological Impacts of Prenatal Melatonin Administration on Reproductive Capacity and Serum Triiodothyronine of Adult Female Offspring Rat Born to Moms Exposed to Bisphenol A During Pregnancy.

Gestational bisphenol A (BPA) exposure induced multiple programmed diseases in the adult offsprings. Thus, this study targeted exploring the physiological impacts of melatonin (MEL) as a reprogramming strategy against in utero BPA exposure on reproductive capacity of adult F1 female rat offspring. Forty adult pregnant albino female rats were divided equally into 5 groups (n = 8): group I (control), group II (low-dose BPA; 25 µg BPA/kg B.w.t.), group III (low-dose BPA + 10 mg MEL/kg B.w.t.), group IV (high-dose BPA; 250 µg/kg B.w.t.), and group V (high-dose BPA + MEL). Treatments were given daily by subcutaneous (s/c) injection from the fourth day of pregnancy until full term. After delivery, female offspring were selected, and on postnatal day 60, adult offspring were examined for estrus regularity and then were sacrificed at estrus to collect blood and tissue samples. Findings clarified that in utero BPA exposure (both doses) increased significantly (P < 0.05) the ovarian weights and the serum levels of estrogen but decreased that of triiodothyronine (T3) compared to control groups. Significant increasing of serum malondialdehyde (MDA) and decreasing of total antioxidant capacity (TAC) were also detected. Both doses of BPA disturbed remarkably the estrus cycles and caused marked aberrations in ovarian and uterine tissues. Interestingly, prenatal MEL co-treatment with BPA mitigated significantly all of these degenerative changes. Thus, this study first demonstrated that prenatal MEL therapy could be used as a potent reprogramming intervention against BPA-induced reproductive disorders in the adult F1 female rat offspring.

Nanonaringenin and Vitamin E Ameliorate Some Behavioral, Biochemical, and Brain Tissue Alterations Induced by Nicotine in Rats.

Nicotine is the major alkaloid present in cigarettes that induces various biochemical and behavioral changes. Nanonaringenin (NNG) and vitamin E are antioxidants that are reported to mitigate serious impairments caused by some toxins and oxidants. Thus, we aimed to investigate the efficacy of NNG, vitamin E, and their combinations to ameliorate behavioral, biochemical, and histological alterations induced by nicotine in rats. Adult male albino rats were randomly grouped into six equal groups (10 rats/group): control, N (nicotine 1 mg/kg b.w./day S/C from 15th to 45th day, 5 days a week), NNG (25 mg/kg b.w./day orally for 45 days), N + NNG, N + E (nicotine + vitamin E 200 mg/kg b.w./day orally), and N + NNG + E (nicotine + NNG + vitamin E at the aforementioned doses). Behavioral tests were conducted on day 15 and 30 postnicotine injection, while memory tests, brain neurotransmitters, antioxidants, and histopathological examination were examined at day 30 only. As a result, nicotine impaired rats' activity (hypoactivity and hyperactivity) and memory, induced anxiolytic and anxiogenic effects on rats, and altered neurotransmitters (acetylcholinesterase, serotonin, and dopamine), and redox markers (MDA, H2O2, GSH, and catalase) levels in brain homogenates. Thickening and congestion of the meninges and degeneration of the cerebral neurons and glia cells were observed. Cosupplementation with NNG, vitamin E, and their combination with nicotine was beneficial in the alleviation of activity impairments and improved short memory and cognition defects and exploratory behaviors. Our results indicate the antioxidant potential of NNG and vitamin E by modulating redox markers and neurotransmitters in the brain. Thus, data suggest that the prophylactic use of NNG, vitamin E, and/or their combination for (45 days) may have a successful amelioration of the disrupted behavior and cognition and biochemical and histopathological alterations induced by nicotine.

Intratracheally Inhalable Nifedipine-Loaded Chitosan-PLGA Nanocomposites as a Promising Nanoplatform for Lung Targeting: Snowballed Protection via Regulation of TGF-ß/ß-Catenin Pathway in Bleomycin-Induced Pulmonary Fibrosis.

Pulmonary fibrosis is a serious ailment that may progress to lung remodeling and demolition, where the key participants in its incidence are fibroblasts responding to growth factors and cellular calcium swinging. Calcium channel blockers, like nifedipine (NFD), may represent auspicious agents in pulmonary fibrosis treatment. Unfortunately, NFD bears complicated pharmacodynamics and a diminished systemic bioavailability. Thus, the current study aimed to develop a novel, non-invasive nanoplatform for NFD for direct/effective pulmonary targeting via intratracheal instillation. A modified solvent emulsification-evaporation method was adopted for the fabrication of NFD-nanocomposites, integrating poly(D,L-lactide-co-glycolide) (PLGA), chitosan (CTS), and polyvinyl alcohol, and optimized for different physiochemical properties according to the 32 full factorial design. Additionally, the aerodynamic behavior of the nanocomposites was scrutinized through cascade impaction. Moreover, the pharmacokinetic investigations were conducted in rats. Furthermore, the optimum formulation was tested in bleomycin-induced pulmonary fibrosis in rats, wherein fibrotic and oxidative stress parameters were measured. The optimum nanocomposites disclosed a nanosized spherical morphology (226.46 nm), a high entrapment efficiency (61.81%) and a sustained release profile over 24 h (50.4%). As well, it displayed a boosted in vitro lung deposition performance with a mass median aerodynamic diameter of 1.12 µm. Pharmacokinetic studies manifested snowballed bioavailability of the optimal nanocomposites by 3.68- and 2.36-fold compared to both the oral and intratracheal suspensions, respectively. The intratracheal nanocomposites revealed a significant reduction in lung fibrotic and oxidative stress markers notably analogous to normal control besides repairing abnormality in TGF-ß/ß-catenin pathway. Our results conferred a compelling proof-of-principle that NFD-CTS-PLGA nanocomposites can function as a promising nanoparadigm for pulmonary fibrosis management.

Physiological Roles of Red Carrot Methanolic Extract and Vitamin E to Abrogate Cadmium-Induced Oxidative Challenge and Apoptosis in Rat Testes: Involvement of the Bax/Bcl-2 Ratio.

The precise analysis of the contents of the red carrot is still ambiguous and its role in the maintenance of male fertility needs to be further reconnoitered. Hence, this study targets the physiological impacts of either red carrot methanolic extract (RCME) or vitamin E (Vit. E), co-administrated with cadmium chloride (CdCl2) on rat testes, specifically those concerned with apoptosis and oxidative challenge. Four groups of adult male rats (n = 12) are used; control, CdCl2, CdCl2 + Vit. E and CdCl2 + RCME. LC-MS analysis of RCME reveals the presence of 20 different phytochemical compounds. Our data clarify the deleterious effects of CdCl2 on testicular weights, semen quality, serum hormonal profile, oxidative markers and Bax/Bcl-2 ratio. Histopathological changes in testicular, prostatic and semen vesicle glandular tissues are also observed. Interestingly, our data clearly demonstrate that co-administration of either RCME or Vit. E with CdCl2 significantly succeeded in the modulation (p < 0.05) of all of these negative effects. The most striking is that they were potent enough to modulate the Bax/Bcl-2 ratio as well as having the ability to correct the impaired semen picture, oxidant status and hormonal profile. Thus, RCME and Vit. E could be used as effective prophylactic treatments to protect the male reproductive physiology against CdCl2 insult.

Thymoquinone and geraniol alleviate cisplatin-induced neurotoxicity in rats through downregulating the p38 MAPK/STAT-1 pathway and oxidative stress.

AIMS: Cisplatin (CP) is a widely used broad-spectrum antineoplastic agent used to treat a variety of human malignancies. Neurotoxicity is clinically evident in patients who have undergone a full course of chemotherapy. The aim of this study was to investigate the possible protective effects of thymoquinone (TQ) and geraniol (Ger) against CP-induced neurotoxicity in rats. MAIN METHODS: Forty male Wistar albino rats were allocated into four groups as follows: normal control, CP-induced neurotoxicity, CP + TQ and CP + Ger. KEY FINDINGS: Our results demonstrated that simultaneous treatment with either TQ or Ger and CP significantly abrogated oxidative stress and downregulated the apoptotic markers p38 mitogen-activated protein kinase (MAPK), STAT-1, p53, p21 and MMP9; FMO3, however, was insignificantly decreased. In addition to the biochemical results, we assessed the histopathological findings, which confirmed the protective effect of TQ and Ger against the brain damage induced by CP. SIGNIFICANCE: The results of the present study indicate that simultaneous treatment with either TQ or Ger as natural antioxidants can provide protection against cisplatin-induced neurotoxicity in rats by attenuating oxidative stress and cell apoptosis.

Protective potential of diclazuril-treated oocysts against coccidiosis in layer chicks.

Diclazuril, which is widely used for the prevention of coccidiosis in chickens, has a lethal effect on asexual and sexual stages of Eimeria spp. However, little is known about its effect on the exogenous stages of Eimeria spp. In this study, we evaluated the effect of in vitro treatment with 0.2% diclazuril on unsporulated and sporulated oocysts of Eimeria spp. For this purpose, a total of 180 male layer chicks aged one day were randomly divided into 5 experimental groups. Each group was divided into 3 replicates of 12 chicks each. Group 1 (G1) and Group 2 (G2) were negative (non-immunized and non-challenged) and positive (non-immunized and challenged) controls, respectively. Group 3 (G3) was immunized per os with 1.0 × 104 non-diclazuril treated-sporulated oocysts. Groups 4 (G4) was immunized per os with 0.2% diclazuril treated-unsporulated oocysts (1.0 × 104) in which diclazzuril didn't affect sporulation. Group 5 (G5) was immunized per os with 0.2% diclazuril treated-sporulated oocysts (1.0 × 104). Chicks of G2, G3, G4, and G5 were challenged with 7.5 × 104 untreated sporulated oocysts at the age of 21 days, while the group 1 chicks remained unchallenged. G4 and G5 animals immunized with 0.2% diclazuril-treated oocysts showed a significant decrease in bloody diarrhea severity, lesion scores, and oocyst counts in comparison to those immunized with untreated oocysts. Furthermore, histopathologic findings showed a low number of parasitic stages in cecal tissues in G4 and G5. A significant increased body weight gain was observed in Gs 4 and 5 in comparison to G2. In addition, expression levels of IL-2, IL-12, and IFN-γ were significantly increased in G4 and G5. In conclusion, diclazuril is effective in attenuating Eimeria oocysts and thus provides an alternative approach for using diclazuril-treated oocysts to protect chicks against Eimeria challenge.

Effects of iron chelating agent on Schistosoma mansoni infected murine model.

Schistosomiasis is one of the major health problems in many tropical and developing countries. Infection takes place once cerceriae penetrate human skin, then it changed into schistosomules. The schistosomules takes iron in the form of heme from host's haemoglobin, ferritin and transferrin. Iron is a vital element not only for growth and sexual maturity of schistosomules to adults but also for oogenesis. Since the trapped eggs are the pathological causative agent for most of pathogenesis and complications, the current work was designed to study the effects of early deprivation of schistosomules from iron in the host (in vivo) by chelating it with deferoxamine (DFO). The iron chelation has effects on growth, maturity and egg deposition, as well as it has ameliorative effects on liver pathology such as hepatic fibrosis. Mice were classified into four groups, normal control, DFO treated only, Schistosoma mansoni (S. mansoni) infected DFO untreated and S. mansoni infected DFO treated. The infected DFO treated mice showed significant reduction in fecal egg excretion with increased percentage of dead eggs and this was accompanied with a significant reduction of both total worm burden and hepatic egg load and increased dead egg percentage compared to the infected DFO untreated group. There was also a significant reduction in both serum and hepatic tissue ferritin concentrations in the infected DFO treated mice in comparison to the infected DFO untreated group. Additionally, a significant decrease in number and size of granulomas with subsequent improvement of liver fibrosis was recorded in the infected DFO treated group. This immunopathology was also associated with significant up regulation of Interlukine12 (IL12), Interferon gamma (IFN γ) and significant down regulation in interleukin4 (IL4), interleukin10 (IL10) in both serum and hepatic tissue in the infected DFO treated compared to other groups. Entirely, DFO succeeded in diminishing the growth, maturity and fecundity of S. mansoni with a subsequent improvement of hepatic pathology. As a result of the above findings, it can be concluded that DFO could be considered as a useful treatment against schistosomal infection.