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.

Metabolomic Profiling and Neuroprotective Effects of Purslane Seeds Extract Against Acrylamide Toxicity in Rat's Brain.

AIM: Acrylamide (ACR) is an environmental pollutant with well-demonstrated neurotoxic and neurodegenerative effects in both humans and experimental animals. The present study aimed to investigate the neuroprotective effect of Portulaca oleracea seeds extract (PSE) against ACR-induced neurotoxicity in rats and its possible underlying mechanisms. PSE was subjected to phytochemical investigation using ultra-high-performance liquid chromatography (UPLC) coupled with quantitative time of flight mass spectrometry (qTOF-MS). Multivariate, clustering and correlation data analyses were performed to assess the overall effects of PSE on ACR-challenged rats. Rats were divided into six groups including negative control, ACR-intoxicated group (10 mg/kg/day), PSE treated groups (200 and 400 mg/kg/day), and ACR + PSE treated groups (200 and 400 mg/kg/day, respectively). All treatments were given intragastrically for 60 days. PSE markedly ameliorated brain damage as evidenced by the decreased lactate dehydrogenase (LDL), increased acetylcholinesterase (AchE) activities, as well as the increased brain-derived neurotrophic factor (BDNF) that were altered by the toxic dose of ACR. In addition, PSE markedly attenuated ACR-induced histopathological alterations in the cerebrum, cerebellum, hippocampus and sciatic nerve and downregulated the ACR-inclined GFAP expression. PSE restored the oxidative status in the brain as indicated by glutathione (GSH), lipid peroxidation and increased total antioxidant capacity (TAC). PSE upregulated the mRNA expression of protein kinase B (AKT), which resulted in an upsurge in its downstream cAMP response element-binding protein (CREB)/BDNF mRNA expression in the brain tissue of ACR-intoxicated rats. All exerted PSE beneficial effects were dose-dependent, with the ACR-challenged group received PSE 400 mg/kg dose showed a close clustering to the negative control in both unsupervised principal component analysis (PCA) and supervised orthogonal partial least square discriminant analysis (OPLS-Da) alongside with the hierarchical clustering analysis (HCA). The current investigation confirmed the neuroprotective capacity of PSE against ACR-induced brain injury, and our findings indicate that AKT/CREB pathways and BDNF synthesis may play an important role in the PSE-mediated protective effects against ACR-triggered neurotoxicity.

Momordica charantia Extract Protects against Diabetes-Related Spermatogenic Dysfunction in Male Rats: Molecular and Biochemical Study.

More than 90% of diabetic patients suffer from sexual dysfunction, including diminished sperm count, sperm motility, and sperm viability, and low testosterone levels. The effects of Momordica charantia (MC) were studied by estimating the blood levels of insulin, glucose, glycosylated hemoglobin (HbA1c), testosterone (TST), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in diabetic rats treated with 250 and 500 mg/kg b.w. of the total extract. Testicular antioxidants, epididymal sperm characteristics, testicular histopathology, and lesion scoring were also investigated. Testicular mRNA expression of apoptosis-related markers such as antiapoptotic B-cell lymphoma-2 (Bcl-2) and proapoptotic Bcl-2-associated X protein (Bax) were evaluated by real-time PCR. Furthermore, caspase-3 protein expression was evaluated by immunohistochemistry. MC administration resulted in a significant reduction in blood glucose and HbA1c and marked elevation of serum levels of insulin, TST, and gonadotropins in diabetic rats. It induced a significant recovery of testicular antioxidant enzymes, improved histopathological changes of the testes, and decreased spermatogenic and Sertoli cell apoptosis. MC effectively inhibited testicular apoptosis, as evidenced by upregulation of Bcl-2 and downregulation of Bax and caspase-3. Moreover, reduction in apoptotic potential in MC-treated groups was confirmed by reduction in the Bax/Bcl-2 mRNA expression ratio.

Propolis ameliorates cerebral injury in focal cerebral ischemia/reperfusion (I/R) rat model via upregulation of TGF-ß1.

Neuroprotective impact of transforming growth factor ß1 (TGF-ß1) is increasingly recognized in different brain injuries. Propolis exhibits a broad spectrum of biological and pharmacological properties including neuroprotective action. The objective of the investigation was to explore the involvement of TGF-ß1 signaling in the neuroprotective mechanism of propolis in I/R rats. In this study, focal cerebral ischemia model was built by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The investigation was carried out on 48 rats that were arranged into four groups (n = 12): the sham group, I/R control group, I/R + propolis (50 mg/kg) group and I/R + propolis (100 mg/kg) group. The results revealed that propolis preserved rats against neuronal injury induced by cerebral I/R. It significantly reduced neurological deficit scores and improved motor coordination and locomotor activity in I/R rats. Propolis antagonized the damage induced by cerebral I/R through suppression of malondialdehyde (MDA) and elevation of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), brain-derived neurotropic factor (BDNF) and dopamine levels in the brain homogenates of I/R rats. Other ameliorations were also observed based on reduction of neurodegeneration and histological alterations in the brain tissues. These results also proposed that the neuroprotective effect of propolis might be related to upregulation of TGF-ß1 and suppressed matrix metallopeptidase-9 (MMP9) mRNA expression.

Olive leaves extract attenuates type II diabetes mellitus-induced testicular damage in rats: Molecular and biochemical study.

Diabetes mellitus (DM) has emerged as a public healthcare problem. Sustained hyperglycemia has been linked with many complications including impaired male fertility Olive tree (Olea europaea L.) leaves have been extensively used in traditional remedies worldwide to control blood glucose level in DM. In this study, the beneficial role of olive leaves extract (OLE) was investigated to combat diabetes-induced adverse effect on testicular tissues. Thirty male Wistar rats were divided into 5 equal groups: normal control group, streptozotocin (STZ)-diabetic group and diabetic groups which were given glibenclamide (GLB) or OLE at 250 and 500 mg/kg for 9 weeks to investigate the efficiency of olive leaves extract (OLE) in reducing the deleterious effect of diabetes on the reproductive system of male rats. Rats were checked for serum glucose, insulin, testosterone and gonadotropins. Also, testicular antioxidants, epididymal sperm characteristics and testicular histopathology were assessed. Expression of the testicular steroidogenic enzymes, cholesterol side-chain cleavage enzyme (P450 scc) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD) was examined. Moreover, androgen receptor and proliferating cell nuclear antigen (PCNA) protein immunohistochemistry were assessed in testes. STZ-induced diabetes significantly increased serum glucose. However, STZ significantly decreased serum levels of insulin, testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Marked reductions in testicular antioxidants with elevated malondialdehyde (MDA) parallel with deterioration of the testicular histoarchitecture and epididymal sperm characteristics were recorded. Administration of GLB or OLE (250 and 500 mg/kg) resulted in a significant recovery of the above mentioned parameters in STZ-diabetic rats. Interestingly, OLE shows greater glycemic improvement and testicular protection than GLB with the highest percentage protection exhibited by the OLE high dose. Furthermore, OLE significantly induced testicular steroidogenesis in diabetic rat as evidenced by elevated P450 scc and 17ß-HSD mRNA expression. The study proves that OLE possesses a potential protective role against diabetes-induced reproductive disorders, which may be due to its antioxidant activity and its ability to normalize testicular steroidogenesis.

Effect of olive leaves extract on the antidiabetic effect of glyburide for possible herb-drug interaction.

The concomitant use of olive leaves (OL) and glyburide (GLB) is a possible therapy for diabetic patients. However, there is no report about the effect of OL on the antidiabetic effect of GLB till now. In the current study, the possible interaction of olive leaves extract (OLE) with GLB was assessed to determine if there was any pharmacological benefit over GLB alone. Seven groups of male Sprague Dawley rats were used. Normal rats of the 1st group treated with 2 mL/kg of 3% Tween 80 (vehicle). The 2nd-5th groups were diabetic rats received vehicle, GLB (5 mg/kg), OLE low dose and OLE high dose respectively, while the 6th-7th groups administered combinations of GLB plus OLE low dose and GLB plus OLE high dose, respectively. All treatments were administered orally once daily for 8 weeks. The use of GLB+OLE-500 obviously improved fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c) in diabetic rats (95.5 ±â€¯5.55 mg/dL, 6.8 ±â€¯0.16 mg/dL and 6.1 ±â€¯0.29%, respectively) compared to those treated with GLB monotherapy (140.0 ±â€¯6.36 mg/dL, 5.4 ±â€¯0.19 mg/dL and 7.0 ±â€¯0.20%, respectively). The lipid profile [triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)] was significantly improved in diabetic rats exposed to GLB+OLE-500 (35.6 ±â€¯1.51 mg/dL, 48.5 ±â€¯2.74 mg/dL, 25.1 ±â€¯1.21 mg/dL and 17.0 ±â€¯0.82 mg/dL, respectively) in comparison with diabetic group exposed to GLB alone (43.2 ±â€¯2.15 mg/dL, 56.8 ±â€¯2.14 mg/dL, 18.6 ±â€¯0.96 mg/dL, 23.0 ±â€¯1.26 mg/dL, respectively). Additionally, the benefit impacts of GLB+OLE-500GLB+OLE-500 therapy on the antioxidant and lipid peroxidation parameters in the pancreatic tissues of diabetic rats were higher than those of GLB monotherapy. Moreover, GLB plus OLE-500 combination had the greatest effect on restoration of the insulin content of Beta (ß) cells and reduction of the glucagon and somatostatin of Alpha (α) and Delta (δ) endocrine cells in the pancreatic islets among the different treatment. The current study suggests that OL and GLB combination could cause herb-drug interactions through modulation of insulin receptor (INR), glucose transporter 2 (Slc2a2) and peroxisome proliferator-activated receptor α (PPAR-α) genes expression in the liver of diabetic rats.

Molecular and biochemical monitoring of the possible herb-drug interaction between Momordica charantia extract and glibenclamide in diabetic rats.

Momordica charantia is used in folk medicine to manage diabetes mellitus. In this study, we investigated the possible herb-drug interaction between M. charantia fruit extract (MCFE) and glibenclamide (GLB) in streptozotocin-diabetic rats. Rats were divided into 7 groups. The 1st group received 3% Tween 80. The 2nd-5th groups were diabetic rats received vehicle, GLB (5 mg/kg), MCFE (250 and 500 mg/kg), respectively. The 6th-7th groups administered GLB plus MCFE (250 and 500 mg/kg), respectively. After 8 weeks, fasting blood glucose (FBG), insulin and glycosylated hemoglobin (HbA1c) levels were assessed. Histopathological and immunohistochemical examinations of the pancreases were done. Quantitative RT-PCR was used to analyze hepatic mRNA expression of insulin receptor (INR), glucose transporter 2 (Slc2a2) and peroxisome proliferator-activated receptor α (PPAR-α) genes. All medicaments greatly reduced FBG in diabetic rats when compared with diabetic control group. GLB plus MCFE combination was better than GLB alone in improving levels of insulin and HbA1c. All medicaments restored insulin content of pancreatic ß-cells and reduced glucagon and somatostatin of alpha and delta endocrine cells. Moreover, GLB plus MCFE-500 was the most efficient in restoring INR, Slc2a2 and PPAR-α mRNA expression to their normal levels. In conclusion, MCFE in combination with GLB gives greater glycemic improvement than GLB monotherapy.

Eutrophication, Ammonia Intoxication, and Infectious Diseases: Interdisciplinary Factors of Mass Mortalities in Cultured Nile Tilapia.

The present study was designed to assess the possible causes of the mass mortalities of Nile Tilapia Oreochromis niloticus at El-Behera Governorate, Egypt, in relationship to environmental and microbiotic factors. Water samples were collected from fish farms at different locations and from Lake Edku to analyze water temperature, water pH, salinity, biological oxygen demand, dissolved oxygen, total ammonia nitrogen, and un-ionized ammonia. A number of moribund and freshly dead fish were sampled and submitted to our laboratory for microbiological, molecular, and histopathological examination. Water analysis of the fish farms revealed noticeable increases in the previously mentioned physicochemical parameters. Clinical examinations of moribund fish showed severe gill rot and massive external and internal hemorrhages. Ordinary and molecular laboratory findings confirmed the presence of Branchiomyces sp. in gill tissue and mixed bacterial fish pathogens (Streptococcus agalactiae, Vibrio alginolyticus, V. parahaemolyticus, Pseudomonas anguilliseptica, and P. aeruginosa) in visceral organs. The histopathological and transmission electron microscopic examinations revealed severe necrosis of gill filaments and blockage of branchial blood vessels and lamellar capillaries with Branchiomyces sp. hyphae and spores mixed with different shapes of bacteria. Severe inflammations were detected in liver, kidney, heart, and brain tissues. Ultimately, we can conclude that the syndrome of mass fish kills in this area is a consequence of ecological damage to the aquatic environment, which is mainly related to natural and anthropogenic factors, as well as to the presence of infectious agents. Received September 30, 2015; accepted April 12, 2016.

Hepatocyte Growth Factor Mediates the Antifibrogenic Action of Ocimum bacilicum Essential Oil against CCl4-Induced Liver Fibrosis in Rats.

The current investigation aimed to evaluate the antifibrogenic potential of Ocimum basilicum essential oil (OBE) and further to explore some of its underlying mechanisms. Three groups of rats were used: group I (control), group II (CCl4 model) and group III (OBE-treated) received CCl4 and OBE 2 weeks after the start of CCl4 administration. Oxidative damage was assessed by the measurement of MDA, NO, SOD, CAT, GSH and total antioxidant capacity (TAC). Liver fibrosis was assessed histopathologically by Masson's trichrome staining and α-smooth muscle actin (α-SMA) immunostaining. Expression of hepatocyte growth factor (HGF) and cytochrome P450 (CYP2EI isoform) was estimated using real-time PCR and immunohistochemistry. OBE successfully attenuated liver injury, as shown by histopathology, decreased serum transaminases and improved oxidative status of the liver. Reduced collagen deposition and α-SMA immuopositive cells indicated an abrogation of hepatic stellate cell activation by OBE. Furthermore, OBE was highly effective in stimulating HGF mRNA and protein expression and inhibiting CCl4-induced CYP2E1 down-regulation. The mechanism of antifibrogenic action of OBE is hypothesized to proceed via scavenging free radicals and activating liver regeneration by induction of HGF. These data suggest the use of OBE as a complementary treatment in liver fibrosis.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.