Differential Impact of Massachusetts, Canadian 4/91, and California (Cal) 1737 Genotypes of Infectious Bronchitis Virus Infection on Lymphoid Organs of Chickens.

Infectious bronchitis virus (IBV) induces severe economic losses in chicken farms due to the emergence of new variants leading to vaccine breaks. The studied IBV strains belong to Massachusetts (Mass), Canadian 4/91, and California (Cal) 1737 genotypes that are prevalent globally. This study was designed to compare the impact of these three IBV genotypes on primary and secondary lymphoid organs. For this purpose, one-week-old specific pathogen-free chickens were inoculated with Mass, Canadian 4/91, or Cal 1737 IBV variants, keeping a mock-infected control. We examined the IBV replication in primary and secondary lymphoid organs. The molecular, histopathological, and immunohistochemical examinations revealed significant differences in lesion scores and viral distribution in these immune organs. In addition, we observed B-cell depletion in the bursa of Fabricius and the spleen with a significant elevation of T cells in these organs. Further studies are required to determine the functional consequences of IBV replication in lymphoid organs.

Comparison of Infectious Bronchitis Virus (IBV) Pathogenesis and Host Responses in Young Male and Female Chickens.

Infectious bronchitis virus (IBV) is an avian coronavirus that causes a disease in chickens known as infectious bronchitis (IB). The pathogenesis of IBV and the host immune responses against it depend on multiple factors such as the IBV variant, breed and age of the chicken, and the environment provided by the management. Since there is limited knowledge about the influence of the sex of chickens in the pathogenesis of IBV, in this study we aim to compare IBV pathogenesis and host immune responses in young male and female chickens. One-week-old specific pathogen-free (SPF) White Leghorn male and female chickens were infected with Canadian Delmarva (DMV)/1639 IBV variant at a dose of 1 × 106 embryo infectious dose (EID)50 by the oculo-nasal route while maintaining uninfected controls, and these chickens were euthanized and sampled 4- and 11-days post-infection (dpi). No significant difference was observed between the infected male and female chickens in IBV shedding, IBV genome load in the trachea, lung, kidney, bursa of Fabricius (BF), thymus, spleen, and cecal tonsils (CT), and IBV-induced lesion in all the examined tissues at both 4 and 11 dpi. In addition, there was no significant difference in the percentage of IBV immune-positive area observed between the infected male and female chickens in all tissues except for the kidney, which expressed an increased level of IBV antigen in infected males compared with females at both 4 and 11 dpi. The percentage of B lymphocytes was not significantly different between infected male and female chickens in all the examined tissues. The percentage of CD8+ T cells was not significantly different between infected male and female chickens in all the examined tissues except in the trachea at 11 dpi, where female chickens had higher recruitment when compared with male chickens. Overall, although most of the findings of this study suggest that the sex of chickens does not play a significant role in the pathogenesis of IBV and the host immune response in young chickens, marginal differences in viral replication and host responses could be observed to indicate that IBV-induced infection in male chickens is more severe.

Replication of infectious bronchitis virus (IBV) Delmarva (DMV)/1639 variant in primary and secondary lymphoid organs leads to immunosuppression in chickens.

Infectious bronchitis virus (IBV) that primarily causes respiratory infection in chickens, disseminate to multiple body systems leading to pathology, results in economic losses to poultry industry. IBV replicates in the bursa of Fabricius (BF), Harderian gland (HG), cecal tonsils (CT), and spleen. The objective of this study was to investigate the immunosuppressive effect of IBV Delmarva (DMV/1639) variant in chickens. Specific pathogen free chickens were infected with the IBV DMV/1639 variant while maintaining an age-matched uninfected control group. At predetermined time points, subsets of the infected and control chickens were observed for changes in body weights and pathological changes. The histopathological lesions were observed in the CT and BF, with minimal lesions in the thymus and spleen. The mRNA expression of pro-inflammatory mediators suggested immunomodulation by IBV, favoring viral replication. Further studies are warranted to observe the functional impact of the IBV DMV/1639 variant's replication in immune organs.

Impact of Maternal Antibodies on Infectious Bronchitis Virus (IBV) Infection in Primary and Secondary Lymphoid Organs of Chickens.

Infectious bronchitis virus (IBV) causes infectious bronchitis disease in chickens. IBV primarily infects the upper respiratory tract and then disseminates to other body systems including gastrointestinal, reproductive, and urinary systems. Unlike original IBV serotypes, the novel IBV variants target lymphoid organs, but information on this is scarce. In this study, we aim to evaluate the impact of the presence of maternal antibodies on IBV infection in primary and secondary lymphoid organs. Maternal antibody free, specific pathogen free (SPF) hens were divided into vaccinated and non-vaccinated groups. The progeny male chicks from these hens were divided into four groups; vaccinated challenged (VC), non-vaccinated challenged (NVC), vaccinated non-challenged (VNC), and non-vaccinated non-challenged (NVNC). The challenge groups were given 1 × 106 embryo infectious dose (EID)50 of IBV Delmarva (DMV)/1639 by the oculo-nasal route and non-challenge groups were given saline. The serum anti-IBV antibody titer was significantly higher in challenged groups compared to non-challenged groups. The IBV genome load was significantly lower in the VC group than NVC group in oropharyngeal and cloacal swabs and in bursa of Fabricius (BF) and cecal tonsils (CT). The histopathological lesion scores were significantly lower in VC group than NVC group in BF and CT. These findings suggest that the presence of maternal antibody in chicks could provide some degree of protection against IBV infection in BF and CT.

The impact of the experimental route of challenge on the host responses and pathogenesis of the Canadian Delmarva (DMV/1639) infectious bronchitis virus infection in laying chickens.

Infectious bronchitis virus (IBV) infection can be associated with respiratory, renal, and/or reproductive diseases in chickens. Under natural conditions, conjunctiva, mucosa of upper respiratory tract, and cloaca are the main routes of IBV entry. Experimentally, the study of IBV infection involved various routes of inoculation. This study investigated the impact of adding the trachea as a potential route of viral entry to the oculo-nasal infection on the host responses, pathogenicity, and tissue tropism of the Canadian IBV Delmarva (DMV/1639) strain in laying chickens. Specific-pathogen-free laying chickens were divided into three experimental groups: control group (Con group), oculo-nasal challenged group (ON group), and oculo-nasal/intratracheal challenged group (ON/IT group); all groups were observed for 12 days post-infection (dpi). The clinical signs and reduction in egg production in the ON/IT group started slightly earlier compared to the ON group. At 12 dpi, the gross lesions in the ON/IT group were confined to the ovary, while the ON group showed regressed ovary and atrophied oviduct. Only the ON group showed significantly higher microscopic lesion scores in the lung, kidney, magnum, and uterus compared to the control group at 12 dpi. The oviduct tissues of the ON group showed a significant increase in B cells infiltration compared to ON/IT and control groups. The viral shedding (detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR)), tissue tropism (detected either by qRT-PCR or immunohistochemistry (IHC)), T/natural killer cells infiltration in reproductive tract (detected by IHC), and antibody-mediated immune responses (measured by enzyme-linked immunosorbent assay) showed similar patterns in the ON and ON/IT groups.

Comparative pathogenicity of infectious bronchitis virus Massachusetts and Delmarva (DMV/1639) genotypes in laying hens.

Infectious bronchitis (IB) is a highly contagious and acute viral disease of chicken caused by the infectious bronchitis virus (IBV) of the family Coronaviridae. Even with extensive vaccination against IB by the poultry industry, the occurrence of new IBV genotypes is a continuous challenge encountered by the global poultry industry. This experiment was designed to compare the pathogenicity of two IBV strains belonging to Massachusetts (Mass) and Delmarva DMV/1639 genotypes. Specific pathogen-free laying hens were challenged during the peak of production (30 weeks), keeping a mock-infected control group. During 21 days of observation following infection, a significant drop in egg production with miss-shaped and soft shells was observed in the DMV/1639 IBV-infected hens only. The DMV/1639 IBV infected group showed prolonged and higher cloacal viral shedding compared with the Mass IBV-infected group. At the end of the study (21 days post-infection), the viral genome loads in the respiratory, urogenital, and immune tissues were significantly higher in the DMV/1639 IBV-infected group compared with the Mass IBV-infected group. Macroscopic lesions such as distorted ova leading to egg peritonitis were observed only in the DMV/1639 IBV-infected group. Moreover, microscopic lesion scores were significantly higher in the lung, kidney, cecal tonsils, and oviduct of the DMV/1639 IBV-infected group compared with the Mass IBV-infected group. Finally, the apoptosis index in the kidney, ovary, magnum, isthmus, and shell gland was significantly higher in the DMV/1639 IBV-infected group compared with the control and Mass-infected groups. This study examined the pathogenicity of two IBV genotypes that are impacting the layer industry in North America.

Protective Effect of Beta-Carotene against Myeloperoxidase- Mediated Oxidative Stress and Inflammation in Rat Ischemic Brain Injury.

Oxidative stress and inflammatory reaction play critical roles in ischemia/reperfusion (I/R) injury in the brain. ß-carotene (ßCAR) is a naturally occurring pigment present in fruits and vegetables that expresses antioxidant and anti-inflammatory activities. This study was conducted to investigate the involvement of Bcl2/Bax and NF-κB signaling pathways in the potential protective role of ßCAR against brain injury in a middle cerebral artery occlusion (MCAO) rat model. A focal brain ischemia model was created for 2 h, followed by reperfusion. Rats were given 10 and 20 mg/kg of ßCAR for 7 days orally before induction of ischemia, at the start of reperfusion, and 3 days after ischemia. Scores of neurological deficit were rated 24 h after induction of ischemia. Motor coordination and spontaneous coordinate activities were assessed using rotarod and activity cage, respectively. After 2 h of the last dose, the animals were killed and their brains were extracted for further examinations. The results of the study show that ßCAR diminished the score of neurological deficits and ameliorated motor coordination, balance, and locomotor activity in the I/R control group. Further, ßCAR resulted in diminution of malondialdehyde (MDA) and augmentation of reduced glutathione (GSH) contents, as well as the elevation of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities in the brain homogenates of I/R rats. ßCAR treatment significantly reduced nuclear factor kappa B (NF-κB) brain content and myeloperoxidase (MPO) activity and ameliorated the histological alterations in the brain tissues. ßCAR significantly suppressed Bcl-2-associated X protein (Bax) and caspase-3 expression, as well as upregulated B-cell lymphoma-2 (Bcl-2) expression, suggesting a neuroprotective potential via downregulating NF-kB and protecting the rat brain against the I/R-associated apoptotic injury.

Vulgarin, a Sesquiterpene Lactone from Artemisia judaica, Improves the Antidiabetic Effectiveness of Glibenclamide in Streptozotocin-Induced Diabetic Rats via Modulation of PEPCK and G6Pase Genes Expression.

The current investigation assessed the effect of the eudesmanolid, Vulgarin (VGN), obtained from Artemisia judaica (A. judaica), on the antidiabetic potential of glibenclamide (GLB) using streptozotocin (STZ) to induce diabetes. Seven groups of rats were used in the study; the first group received the vehicle and served as normal control. The diabetic rats of the second to the fifth groups were treated with the vehicle (negative control), GLB at 5 mg/kg (positive control), VGN at 10 mg/kg (VGN-10) and VGN at 20 mg/kg (VGN-20), respectively. The diabetic rats of the sixth and seventh groups were administered combinations of GLB plus VGN-10 and GLB plus VGN-20, respectively. The diabetic rats treated with GLB plus VGN-20 combination showed marked improvement in the fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c), as well as the lipid profile, compared with those treated with GLB alone. Further, the pancreatic tissues of the diabetic rats that received the GLB+VGN-20 combination showed superior improvements in lipid peroxidation and antioxidant parameters than those of GLB monotherapy. The insulin content of the ß-cells was restored in all treatments, while the levels of glucagon and somatostatin of the α- and δ-endocrine cells were reduced in the pancreatic islets. In addition, the concurrent administration of GLB+VGN-20 was the most effective in restoring PEPCK and G6Pase mRNA expression in the liver. In conclusion, the results demonstrated that the GLB+VGN-20 combination led to greater glycemic improvement in diabetic rats compared with GLB monotherapy through its antioxidant effect and capability to modulate PEPCK and G6Pase gene expression in their livers.

Crataegus sinaica defatted methanolic extract ameliorated monosodium iodoacetate-induced oxidative stress andinhibited inflammation in a rat model of osteoarthritis.

Background and purpose: Osteoarthritis is a degenerative joint disease without definite treatment. It is characterized by intra-articular inflammation, cartilage degeneration, subchondral bone remodeling, and joint pain. The objective of the current study was to assess the anti-osteoarthritic effect and the possible underlying mechanism of action of Crataegus sinaica extract (CSE). Experimental approach: Intra-articular injection of monosodium iodoacetate in the right knee joint of all rats was done except for the sham group. One week later, the anti-inflammatory efficacy of CSE (100, 200, 300 mg/kg, daily p.o) for 4 successive weeks versus ibuprofen (40 mg/kg, p.o) was assessed. Serum inflammatory cytokines; as well as weekly assessment of knee joint swelling, joint mobility, and motor coordination were done. At the end of the experiment, a histopathological investigation of the affected knee joints and an x-ray investigation were also executed. Findings / Results: CSE significantly decreased joint swelling, pain behaviors, and serum levels of TNF-α, IL6, hyaluronic acid, and CTX-II. The radiographic findings revealed almost normal joint space with normal radiodensity and diameter in CSE-treated rats. As well, the histopathological and immunohistochemical investigations of the knee joints in CSE-treated groups retained the cartilage structure of knee joints. A significant reduction in the percentage of caspase-3-stained chondrocytes and a decrease in TGF-ß1 immuno-positive areas in the synovial lining and sub lining were recorded in CSE-treated rats, compared to the osteoarthritis control group. Conclusion and implications: This study approved the chondroprotective effects of CSE, and its ability to inhibit the pain associated with osteoarthritis.

D-Carvone Attenuates CCl4-Induced Liver Fibrosis in Rats by Inhibiting Oxidative Stress and TGF-ß 1/SMAD3 Signaling Pathway.

D-carvone is a natural monoterpene found in abundance in the essential oil of aromatic medicinal plants with a wide range of pharmacological values. However, the impact of D-carvone on liver fibrosis remains unclear. This study aimed to evaluate the anti-fibrotic potential of D-carvone in a rat model of liver fibrosis and to clarify the possible underlying mechanisms. Liver fibrosis was induced in rats by carbon tetrachloride, CCl4 (2.5 mL/kg, interperitoneally every 72 h for 8 weeks). Oral treatment of rats with D-carvone (50 mg/kg, daily) started on the 3rd week of CCl4 administration. D-carvone significantly enhanced liver functions (ALT, AST), oxidant/antioxidant status (MDA, SOD, GSH, total antioxidant capacity; TAC), as well as histopathological changes. Moreover, D-carvone effectively attenuated the progression of liver fibrosis, evident by the decreased collagen deposition and fibrosis score by Masson trichrome staining (MT) and α-SMA protein expression. Moreover, D-carvone administration resulted in a significant downregulation of the pro-fibrogenic markers TGF-ß1 and SMAD3 and upregulation of MMP9. These findings reveal the anti-fibrotic effect of D-carvone and suggest regulation of the TGF-ß1/SMAD3 pathway, together with the antioxidant activity as a mechanistic cassette, underlines this effect. Therefore, D-carvone could be a viable candidate for inhibiting liver fibrosis and other oxidative stress-related hepatic diseases. Clinical studies to support our hypothesis are warranted.

Thymol ameliorated neurotoxicity and cognitive deterioration in a thioacetamide-induced hepatic encephalopathy rat model; involvement of the BDNF/CREB signaling pathway.

In the present study, we aimed to delineate the neuroprotective potential of thymol (THY) against neurotoxicity and cognitive deterioration induced by thioacetamide (TAA) in an experimental model of hepatic encephalopathy (HE). Rats received TAA (100 mg kg-1, intraperitoneally injected, three times per week) for two weeks. THY (30 and 60 mg kg-1), and Vit E (100 mg k-1) were administered daily by oral gavage for 30 days after HE induction. Supplementation with THY significantly improved liver function, reduced serum ammonia level, and ameliorated the locomotor and cognitive deficits. THY effectively modulated the alteration in oxidative stress markers, neurotransmitters, and brain ATP content. Histopathology of liver and brain tissues showed that THY had ameliorated TAA-induced damage, astrocyte swelling and brain edema. Furthermore, THY downregulated NF-kB and upregulated GFAP protein expression. In addition, THY significantly promoted CREB and BDNF expression at both mRNA and protein levels, together with enhancing brain cAMP level. In conclusion, THY exerted hepato- and neuroprotective effects against HE by mitigating hepatotoxicity, hyperammonemia and brain ATP depletion via its antioxidant, anti-inflammatory effects in addition to activation of the CREB/BDNF signaling pathway.

Miconazole Mitigates Acetic Acid-Induced Experimental Colitis in Rats: Insight into Inflammation, Oxidative Stress and Keap1/Nrf-2 Signaling Crosstalk.

Ulcerative colitis (UC) is the most common type of inflammatory bowel disease, characterized by oxidative stress and elevated pro-inflammatory cytokines. Miconazole is an azole antifungal that stimulates the expression of antioxidant enzymes via Nrf2 activation, which consequently inhibits ROS formation and NF-κB activation. Hence, the present study aimed to investigate the protective effect of miconazole, sulfasalazine (as a reference drug) and their combination on acetic acid (AA)-induced UC in a rat model which was induced by intra-rectal administration of 4% AA. Rats were pretreated with miconazole (20 and 40 mg/kg, orally) or sulfasalazine (100 mg/kg, orally), or their combination (20 mg/kg miconazole and 50 mg/Kg of sulfasalazine, orally). Pretreatment with miconazole significantly reduced wet colon weight and macroscopic scores, accompanied by a significant amelioration of the colonic architecture disorder. Moreover, the treatment also significantly decreased the malondialdehyde (MDA) level and prevented the depletion of superoxide dismutase (SOD) activity and GSH content in inflamed colons. Additionally, the treatment showed suppressive activities on pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP), and upregulated the anti-inflammatory cytokine interleukin-10 (IL-10). Moreover, the treatment upregulated the protein levels of Nrf-2 and heme oxygenase-1 (HO-1) in the colon tissue. Taken together, miconazole is effective in alleviating AA-induced colitis in rats, and the mechanism of its action is associated with the activation of Nrf2-regulated cytoprotective protein expression.

Possible Synergistic Antidiabetic Effects of Quantified Artemisia judaica Extract and Glyburide in Streptozotocin-Induced Diabetic Rats via Restoration of PPAR-α mRNA Expression.

Several members of the genus Artemisia are used in both Western and African traditional medicine for the control of diabetes. A considerable number of diabetic patients switch to using oral antidiabetic drugs in combination with certain herbs instead of using oral antidiabetic drugs alone. This study examined the effect of Artemisia judaica extract (AJE) on the antidiabetic activity of glyburide (GLB) in streptozotocin (STZ)-induced diabetes. Forty-two male Wistar rats were divided into seven equal groups. Normal rats of the first group were treated with the vehicle. The diabetic rats in the second-fifth groups received vehicle, GLB (5 mg/kg), AJE low dose (250 mg/kg), and AJE high dose (500 mg/kg), respectively. Groups sixth-seventh were treated with combinations of GLB plus the lower dose of AJE and GLB plus the higher dose of AJE, respectively. All administrations were done orally for eight weeks. Fasting blood glucose (FBG) and insulin levels, glycated hemoglobin (HbA1c) percentage, serum lipid profile, and biomarkers of oxidative stress were estimated. The histopathological examination of the pancreas and the immunohistochemical analysis of anti-insulin, anti-glucagon, and anti-somatostatin protein expressions were also performed. The analysis of the hepatic mRNA expression of PPAR-α and Nrf2 genes were performed using quantitative RT-PCR. All treatments significantly lowered FBG levels when compared with the STZ-control group with the highest percentage reduction exhibited by the GLB plus AJE high dose combination. This combination highly improved insulin levels, HbA1c, and lipid profile in blood of diabetic rats compared to GLB monotherapy. In addition, all medicaments restored insulin content in the ß-cells and diminished the levels of glucagon and somatostatin of the α- and δ-endocrine cells in the pancreatic islets. Furthermore, the GLB plus AJE high dose combination was the most successful in restoring PPAR-α and Nrf2 mRNA expression in the liver. In conclusion, these data indicate that the GLB plus AJE high dose combination gives greater glycemic improvement in male Wistar rats than GLB monotherapy.

Novel promising reproductive and metabolic effects of Cicer arietinum L. extract on letrozole induced polycystic ovary syndrome in rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Chickpea was used in both greek and indian traditional medicine for hormonal related conditions as menstrual induction, acceleration of parturation, treatment of retained placenta and stimulation of lactation. Chickpea (Cicer arietinum) sprout isoflavone isolates exhibited reasonable estrogenic activities. Isoflavones, a subtype of phytoestrogens, are plant derivatives with moderate estrogenic activity that tend to have protective effects on hormonal and metabolic abnormalities of women with polycystic ovary syndrome (PCOS). AIM OF THE STUDY: In this study, we investigated the effect of UPLC/ESI-MS characterized Cicer arietinum L. seeds ethanol extract (CSE) on ovarian hormones, oxidative response and ovarian histological changes on induced PCOS rat model. MATERIALS AND METHODS: Thirty-five rats were divided into five groups including negative control, PCOS, and treatment groups. PCOS was induced using letrozole (1 mg/kg) daily orally for 21 days. Each treatment group was treated with one of the following for 28 days after induction of PCOS: clomiphene citrate (1 mg/kg), and CSE at 250 and 500 mg/kg. Ovaries and uteri were excised, weighed and their sections were used for quantitative real-time reverse transcriptase polymerase chain reaction, antioxidant assays and histomorphometric study of the ovaries. The antioxidant assays, histopathological examination, hormonal and metabolic profiles, and Cyp11a1(steroidogenic enzyme) mRNA expression were measured. RESULTS: In all treatment groups, ovarian weight was significantly decreased despite having no significant effect on uterine weight. Histomorphometric study in the treatment groups revealed a significant decrease in the number and diameter of cystic follicles, a significant increase in granulosa cell thickness while, thickness of theca cells was significantly decreased when compared to PCOS. Hormone levels, metabolic profile and antioxidant status were improved in the treatment groups. Moreover, Cyp11a1 mRNA expression was significantly downregulated in the treatment groups compared to PCOS. CONCLUSIONS: In the current study, CSE enhanced the reproductive and metabolic disorders which were associated with PCOS induction. For the first time, we have highlighted the effect of CSE in treating PCOS and its associated manifestations.

Eruca sativa seed extract modulates oxidative stress and apoptosis and up-regulates the expression of Bcl-2 and Bax genes in acrylamide-induced testicular dysfunction in rats.

Acrylamide (ACR) has been previously associated with male sexual dysfunction and infertility. Eruca sativa (L.) (arugula or rocket) have been widely used in traditional remedies in Mediterranean region and western Asia and was known for its strong aphrodisiac effect since Roman times. The current study was designed to investigate LC/MS analysis of total ethanol extract Eruca sativa (L.) and the efficiency and mechanism of action of Eruca sativa seed extract (ESS) in reducing hypogonadism induced by acrylamide in male rats. Male Wistar rats were divided into 6 groups (n = 7): control group, Eruca sativa seed extract (ESS) at doses of 100 and 200 mg\kg, acrylamide (ACR), ACR + ESS 100 mg/kg, and ACR + ESS 200 mg/kg. The animals received ACR at a dose of 10 mg/kg b.wt for 60 days. Sperm indices, testicular oxidative stress, testosterone hormone, and testicular histopathology and immunohistochemistry of PCNA and caspase-3 were investigated. Moreover, the expression level of testicular B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) genes was evaluated. In respect to the LC/MS of total ethanol extract Eruca sativa (L.) seed revealed tentative identification of 39 compounds, which belongs to different classes as sulphur-containing compounds, flavonoids, phenolic acid, and fatty acids. Administration of ESS extract (100, 200 mg/kg) improved semen quality, diminished lipid peroxidation, enhanced testicular antioxidant enzyme, restored serum testosterone level, and reduced testicular degeneration and Leydig cell death in the rats intoxicated with ACR. However, the effects of ESS at the dose of 200 mg/kg were similar to that of control group. Furthermore, ESS treatment significantly induced anti-apoptotic effect indicated by elevation of both Bcl-2 and Bax expressions. Nutriceutics of ESS extract protects testis against ACR-induced testicular toxicity via normalizing testicular steroidogenesis, keeping Leydig cells, and improving oxidative stress status.

Benzyl isothiocyanates modulate inflammation, oxidative stress, and apoptosis via Nrf2/HO-1 and NF-κB signaling pathways on indomethacin-induced gastric injury in rats.

The present study investigated the gastroprotective activity of benzyl isothiocyanates (BITC) on indomethacin (IND)-induced gastric injury in a rat model and explicated the possible involved biochemical, cellular, and molecular mechanisms. The rat model with gastric ulcers was established by a single oral dose of IND (30 mg per kg b.wt). BITC (0.75 and 1.5 mg kg-1) and esomeprazole (20 mg per kg b.wt) were orally administered for 3 weeks to rats before the induction of gastric injury. Compared with the IND group, BITC could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. BITC significantly preserved the antioxidants (glutathione GSH, superoxide dismutase SOD), nitric oxide (NO), and prostaglandin E2 (PGE2) contents, while decreasing the gastric mucosal malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and myeloperoxidase (MPO) contents. Moreover, BITC remarkably upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NAD(P)H : quinone oxidoreductase (NQO1). In addition, BITC activates the expression of heat shock protein 70 (HSP-70) and downregulated the expression of nuclear factor-κB (NF-κB) and caspase-3 to promote gastric mucosal cell survival. To the best of our knowledge, this study is the first published report to implicate the suppression of inflammation, oxidative stress, and Nrf2 signaling pathway as a potential mechanism for the gastroprotective activity of BITC.

Analysis of the Productivity, Immunity, and Health Performance of Nile Tilapia (Oreochromis niloticus) Broodstock-fed Dietary Fermented Extracts Sourced from Saccharomyces cerevisiae (Hilyses): A Field Trial.

The present study aimed to evaluate the effect of dietary fermented extracts sourced from Saccharomyces cerevisiae (nucleotides, ß-glucans and MOS) (Hilyses®) on the production and health of Nile tilapia (Oreochromis niloticus) broodstock, as well as on seed survival and performance. The trial was performed in a hatchery along the spawning season and continued in the laboratory to monitor the performance in fry and fingerlings. The broodstock were divided into two groups, (C) fed a basal diet and (H) fed 0.4% Hilyses. Blood and histological parameters, antioxidant power, cortisol level and the expression of some immune-related (TLR-2, IL-1ß and TNF-α) and growth-related genes (MUC-2 and IGF-1) were measured. The obtained seeds were subdivided into four treatments: (C-C) fed a basal diet, (C-H) fed 0.4% Hilyses, (H-C) fed a basal diet and (H-H) fed 0.4% Hilyses. Results revealed that the dietary inclusion of Hilyses in the broodstock increased seed production, survival, hematological parameters, and antioxidant power. Moreover, it improved the intestinal microstructure and upregulated the immune- and growth-related genes. The growth indices of fry and fingerlings were significantly increased in all Hilyses-treated groups (p < 0.05). The performance in the (H-H) group significantly surpassed those of all groups. Therefore, dietary fermented yeast could be used as a strategic solution to sustain tilapia production.

Portulaca oleracea seeds' extract alleviates acrylamide-induced testicular dysfunction by promoting oxidative status and steroidogenic pathway in rats.

BACKGROUND: Acrylamide (ACR) is a widespread industrial and food contaminant that garnered considerable attention for its carcinogenic, neurotoxic, and reproductive toxic effects. The antioxidant effects of Portulaca oleracea seeds extract (POS) and its fertility-enhancing effects were inspiring to evaluate the protective potential and pinpoint the mechanisms and molecular targets of the UPLC-MS fingerprinted POS extract on ACR-induced testicular toxicity in rats. METHODS: Male Wistar rats were divided into 6 equal groups of negative control, ACR model (10 mg/kg b.wt.), POS at doses of (200 and 400 mg/kg b.wt.) and POS-treated ACR groups. All treatments were given by oral dosing every day for 60 days. RESULTS: Administration of POS extract reversed the ACR-induced epididymides weight loss with improved semen quality and count, ameliorated the ACR-decreased testicular lesion scoring, testicular oxidative stress, testicular degeneration, Leydig cell apoptosis and the dysregulated PCNA and Caspase-3 expression in a dose-dependent manner. It upregulated the declined level of serum testosterone and the expression of steroidogenic genes such as CYP11A1 and 17ß3-HSD with an obvious histologic improvement of the testes with re-establishment of the normal spermatogenic series, Sertoli and Leydig cells. CONCLUSIONS: The supplementation with POS extract may provide a potential protective effect for ACR-induced testicular dysfunction which is mediated by its antioxidant, antiapoptotic and steroidogenic modulatory effects.

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: promising activity without the risk of hepatic adverse effect.

BACKGROUND: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products. METHODS: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS). RESULTS: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes. CONCLUSION: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk.

Artemisia judaica L. diminishes diabetes-induced reproductive dysfunction in male rats via activation of Nrf2/HO-1-mediated antioxidant responses.

Diabetes mellitus is a well-known danger element for the progression of male reproductive dysfunctions. Available evidence supports oxidative stress to be the underlying mechanism for the manifestation of testicular dysfunctions during diabetes, and this relation represents an attractive target to antagonize these complications. Artemisia judaica L. is known to have antidiabetic and antioxidant characteristics. The possible protective effect of Artemisia judaica against diabetes-induced testicular disorders was not explored. In this investigation, we planned to estimate the possible protective effect of Artemisia judaica extract against diabetes-induced testicular disorders in male rats. The blood levels of insulin, glucose, glycosylated hemoglobin, testosterone, luteinizing hormone and follicle stimulating hormone were evaluated in rats after 12 weeks of Artemisia judaica treatment. Further, oxidative stress markers were determined in their testicular tissue. Epididymal fluid and testicular histological changes were also assessed. Expression of proliferating cell nuclear antigen has been evaluated in testis. Testicular mRNA expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 as the significant transcription factors in controlling antioxidant system were evaluated by real-time polymerase chain reaction. Artemisia judaica extracts have the ability to ameliorate the elevation in the serum glucose and blood glycosylated hemoglobin and the reduction in insulin, testosterone, follicle stimulating hormone and luteinizing hormone caused by streptozotocin-induced diabetes. It induced a significant recovery of the testicular oxidative stress markers, sperm characteristics and improved histopathological findings of the testes. Treatment with Artemisia judaica extracts led to an increase in proliferating cell nuclear antigen protein expression. Reduction of testicular oxidative stress potential in streptozotocin-treated groups was confirmed by upregulation of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1.