Preclinical efficacy of oral and nasal rivastigmine-loaded chitosan nano-particles on AlCl3-induced Alzheimer's-like disease in rats.

The successful treatment of Alzheimer's disease (AD) is still a big challenge. Rivastigmine is one of the most used drugs for the treatment of AD. The short half-life, lower bioavailability, and less concentration of the drug in the brain after oral delivery are considered the main drawbacks of rivastigmine. To improve these drawbacks, nanostructure-mediated drug delivery has gained more attention. This study investigates the effect of rivastigmine-loaded in optimized chitosan nano-particles (RS-CSNPs) as polymeric nano-carriers by different administration routes (oral and intranasal) on aluminum chloride (AlCl3)-induced Alzheimer-like disease in rat. The model was established by giving rats 100 mg/kg/b.wt of AlCl3 orally for 3 months. Then the experimental rats were treated with RS-CSNPs either orally or intranasally for 75 days. Histopathology, immunohistochemistry of Tau expression in brain tissue, and gene expression of Caspase-3, NF-κB, and Nrf-2 were carried out. The therapeutic agents used decreased the alterations observed in AlCl3 group with improvement in the neuronal viability. In addition to low expression of tau protein, down-regulation of caspase-3 and NF-κB genes and up-regulation of Nrf-2. RS-CSNPs alleviated the progression of AD presumably via blocking the inflammatory cascade and decreasing the oxidative stress process. The intranasal route is superior to the oral one and promising in AD management.

Alirocumab boosts antioxidant status and halts inflammation in rat model of sepsis-induced nephrotoxicity via modulation of Nrf2/HO-1, PCSK9/HMGB1/NF-ᴋB/NLRP3 and Fractalkine/CX3CR1 hubs.

Acute kidney injury (AKI) is a devastating consequence of sepsis, accompanied by high mortality rates. It was suggested that inflammatory pathways are closely linked to the pathogenesis of lipopolysaccharide (LPS)-induced AKI. Inflammatory signaling, including PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-κB, NLRP3/caspase-1 and Fractalkine/CX3CR1 are considered major forerunners in this link. Alirocumab, PCSK9 inhibitor, with remarkable anti-inflammatory features. Accordingly, this study aimed to elucidate the antibacterial effect of alirocumab against E. coli in vitro. Additionally, evaluation of the potential nephroprotective effects of alirocumab against LPS-induced AKI in rats, highlighting the potential underlying mechanisms involved in these beneficial actions. Thirty-six adult male Wistar rats were assorted into three groups (n=12). Group I; was a normal control group, whereas sepsis-mediated AKI was induced in groups II and III through single-dose intraperitoneal injection of LPS on day 16. In group III, animals were given alirocumab. The results revealed that LPS-induced AKI was mitigated by alirocumab, evidenced by amelioration in renal function tests (creatinine, cystatin C, KIM-1, and NGAL); oxidative stress biomarkers (Nrf2, HO-1, TAC, and MDA); apoptotic markers and renal histopathological findings. Besides, alirocumab pronouncedly hindered LPS-mediated inflammatory response, confirmed by diminishing HMGB1, TNF-α, IL-1ß, and caspase-1 contents; the gene expression of PCSK9, RAGE, NF-ᴋB and Fractalkine/CX3CR1, along with mRNA expression of TLR4, MYD88, and NLRP3. Regarding the antibacterial actions, results showed that alirocumab displayed potential anti-bacterial activity against pathogenic gram-negative E. coli. In conclusion, alirocumab elicited nephroprotective activities against LPS-induced AKI via modulation of Nrf2/HO-1, PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-ᴋB/NLRP3/Caspase-1, Fractalkine/CX3R1 and apoptotic axes.

Platelet-rich plasma attenuates the UPEC-induced cystitis via inhibiting MMP-2,9 activities and downregulation of NGF and VEGF in Canis Lupus Familiaris model.

One of the most prevalent disorders of the urinary system is urinary tract infection, which is mostly brought on by uropathogenic Escherichia coli (UPEC). The objective of this study was to evaluate the regenerative therapeutic and antibacterial efficacy of PRP for induced bacterial cystitis in dogs in comparison to conventional antibiotics. 25 healthy male mongrel dogs were divided into 5 groups (n = 5). Control negative group that received neither induced infection nor treatments. 20 dogs were randomized into 4 groups after two weeks of induction of UPEC cystitis into; Group 1 (control positive; G1) received weekly intravesicular instillation of sodium chloride 0.9%. Group 2 (syst/PRP; G2), treated with both systemic intramuscular antibiotic and weekly intravesicular instillation of PRP; Group 3 (PRP; G3), treated with weekly intravesicular instillation of PRP, and Group 4 (syst; G4) treated with an intramuscular systemic antibiotic. Animals were subjected to weekly clinical, ultrasonographic evaluation, urinary microbiological analysis, and redox status biomarkers estimation. Urinary matrix metalloproteinases (MMP-2, MMP-9) and urinary gene expression for platelet-derived growth factor -B (PDGF-B), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were measured. At the end of the study, dogs were euthanized, and the bladder tissues were examined macroscopically, histologically, and immunohistochemically for NF-κB P65 and Cox-2. The PRP-treated group showed significant improvement for all the clinical, Doppler parameters, and the urinary redox status (p < 0.05). The urinary MMPs activity was significantly decreased in the PRP-treated group and the expression level of urinary NGF and VEGF were downregulated while PDGFB was significantly upregulated (p < 0.05). Meanwhile, the urinary viable cell count was significantly reduced in all treatments (P < 0.05). Gross examination of bladder tissue showed marked improvement for the PRP-treated group, expressed in the histopathological findings. Immunohistochemical analysis revealed a marked increase in Cox-2 and NF-κB P65 in the PRP-treated group (P < 0.05). autologous CaCl2-activated PRP was able to overcome the bacterial infection, generating an inflammatory environment to overcome the old one and initiate tissue healing. Hence, PRP is a promising alternative therapeutic for UPEC cystitis instead of conventional antibiotics.

The effects of dietary Spirulina platensis or curcumin nanoparticles on performance, body chemical composition, blood biochemical, digestive enzyme, antioxidant and immune activities of Oreochromis niloticus fingerlings.

CONTEXT: Recently, prioritize has been given to using natural phytogenic or nano compounds as growth promoters and immunostimulants in fish diets as an alternative to antibiotics. AIMS: The main propose of this trial was to determine the impact of supplementing diets with spirulina or curcumin nanoparticles on the performance and health indicators of Nile tilapia fingerlings. METHODS: In a 56-day feeding trial, 180 tilapia fingerlings were assigned into three main groups, as follows: 1st, control group, 2nd, Spirulina platensis (SP; 5 g kg-1 diet) and 3rd, curcumin nanoparticles (CUR-NPs; 30 mg kg-1 diet). KEY RESULTS: Incorporating tilapia diets with SP or CUR-NPs significantly improved performance, body chemical analysis, blood biochemical and hematological indices, digestive enzyme activities, and antioxidant and immunostimulant features compared to the control. CONCLUSION: Fortified tilapia diets with CUR-NPs or SP efficiently boost the productivity and health of Nile tilapia fingerlings. IMPLICATIONS: The research introduces new practical solutions for applying safe feed additives as alternatives to antibiotics in tilapia farming.

Effect of pyometra on vascularity alterations, oxidative stress, histopathology and inflammatory molecules in feline.

This study aimed to investigate blood flow, hemodynamical features by Doppler ultrasound, the oxidative stress biomarkers from serum samples, and histopathology from uterine tissue, in healthy queens and queens with pyometra. Twenty queens were categorized into two groups, according to signs, history, and ultrasound findings, as pyometra and control healthy queens. Doppler ultrasonography, total antioxidant capacity (TAC), malondialdehyde (MDA), albumin, bacteriological isolation, histopathology, and immunohistochemistry of tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa B (NF-κB) P65 were performed. Uterine diameter and thickness increased significantly in the pyometra group compared to control. Uterine peak velocity and flow rate were significantly higher in the control group. The pyometra group showed a significant decrease in albumin, TAC, and a significant increase in MDA. Fibrosis and mononuclear inflammatory cell infiltration were seen in the pyometra samples. The mean area percentage of TNF-α expression in the uteri of the pyometra group was higher. The expression of NF-κB P65 in the uteri in the pyometra group was significantly higher. Doppler ultrasonography can provide valuable information for diagnosing pyometra in queens by elevating the uterine thickness with reducing blood flow rate. Oxidative stress, TNF-α, and NF-κB expression alterations varied between pyometra and control groups.

Spirulina platensis as a growth booster for broiler; Insights into their nutritional, molecular, immunohistopathological, and microbiota modulating effects.

BACKGROUND: The present study is designed to assess the effect of adding various doses of Spirulina platensis (SP) on broiler chicken growth performance, gut health, antioxidant biomarkers, cecal microbiota, histopathology, and immunohistochemistry of inducible nitric oxide synthase (iNOS). 240 male Cobb 500 broiler chicks (1 day old) were placed into four groups (sixty birds/group), then each group was further divided into three replicates of 20 chickens each for 35 days. Birds were allocated as follows; the 1st group (G1), the control group, fed on basal diet, the 2nd group (G2): basal diet plus SP (0.1%), the 3rd group (G3): basal diet plus SP (0.3%), and the 4th group (G4): basal diet plus SP (0.5%). RESULTS: Throughout the trial (d 1 to 35), SP fortification significantly increased body weight growth (BWG) and feed conversion rate (FCR) (P < 0.05). Bursa considerably increased among the immunological organs in the Spirulina-supplemented groups. Within SP-supplemented groups, there was a substantial increase in catalase activity, blood total antioxidant capacity, jejunal superoxide dismutase (SOD), and glutathione peroxidase (GPX) activity (P < 0.05). Fatty acid binding protein 2 (FABP2), one of the gut barrier health biomarkers, significantly increased in the SP-supplemented groups but the IL-1ß gene did not significantly differ across the groups (P < 0.05). Different organs in the control group showed histopathological changes, while the SP-supplemented chicken showed fewer or no signs of these lesions. The control group had higher levels of iNOS expression in the gut than the SP-supplemented groups (p < 0.05). Cecal Lactobacillus count significantly elevated with increasing the rate of SP inclusion rate (p < 0.05). CONCLUSION: Supplementing broiler diets with SP, particularly at 0.5%, can improve productivity and profitability by promoting weight increase, feed utilization, antioxidant status, immunity, and gastrointestinal health.

Phylogeny and ultrastructure of Elthusa raynaudii (Isopoda, Cymothoidae) firstly recorded from the invasive silver cheeked toadfish (Lagocephalus sceleratus) (Gmelin 1789) in eastern Mediterranean Sea coast.

With the opening of the Suez Canal in 1869, many changes have occurred in the Mediterranean Sea ecosystem so became a home to many invasive Lessepsian marine species that have migrated from the Red Sea. About 500 marine species including pufferfish have immigrated and rapidly established a population in the Mediterranean Sea causing significant impact on its ecosystem and fisheries sector. The parasitic fauna of these pufferfish has scarcely been studied in the Mediterranean Sea and also in their native habitat. During this surveillance study on the invasive pufferfish species from the Egyptian Mediterranean coast, the female cymothoid isopod Elthusa raynaudii was detected from the branchial cavity and also in the buccal cavity of 23.9% of the examined Lagocephalus sceleratus. The isolated isopod species was firstly identified and described through electron microscopy and molecular phylogeny based on the sequences of mitochondrial 16S rRNA gene. Additionally, the description of eggs, embryonic stage, and manca of E. raynaudii was firstly provided. The pathological impact on the infested fish tissues was investigated and revealed curling and loss of secondary gill lamellae in addition to mucous exudates in between the gill filaments and granuloma formation in the gill arch. The study provided the first report of L. sceleratus as a new host for the isopod E. raynaudii collected from the Egyptian Mediterranean coast as a new locality record. The role of the Lessepsian invasive pufferfish in transmitting parasites to the native fish species was discussed.

The influence of Spirulina extract on pathogenicity, immune response, and vaccine efficacy against H9N2 avian influenza virus in specific pathogen free chickens.

Avian influenza (AI) viruses pose a risk to the worldwide poultry industry. Ultimately, improving the efficiency of the H9N2 vaccine is necessary to better control low-pathogenic avian influenza-H9N2 by using natural immunostimulant. Therefore, the goal of the present study was to examine varying doses of the cyanobacterium Spirulina extract on the effectiveness of H9N2 vaccine. Thus, a total of 150 specific pathogen-free (SPF) chickens were allocated into 6 groups, 25 birds each, as follow: G1, G2, and G6 were supplemented with 200, 400, and 400 mg Spirulina extract/kg feed, respectively, whilst the feed in G3, G4, and G5 were not supplemented with Spirulina extract. At 21-days-old, only the chickens in G1, G2, and G3 were vaccinated with the H9N2 AI vaccine. After 4 wk postvaccination, the chickens in G1, G2, G3, G4, and G6 were challenged with H9N2 AI Egyptian strain. The challenged virus was selected from a recent circulating Egyptian strain during 2022, and it was related to A/quail/Hong Kong/G1/97-like virus lineage and clustered with G1-B sub-lineage EGY-2 group. It had a high amino acids identity percentage of 92.6% with the A/chicken/Iran/av1221/1998 (Boehringer Ingelheim) vaccine. The results of real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR) revealed that no shedding of the virus was reported in G1, G2, G3, and G5. The supplementation of Spirulina extract in low (200 mg/kg of feed) and high (400 mg/kg of feed) concentration with the birds vaccinated with H9N2 AI vaccine (G1 and G2) induced prominent immuno-stimulatory effect in a dose dependent manner where it strongly enhanced the phagocytic activities of broilers' peripheral blood monocytes, and lysozyme at all days postvaccination (dpv) and days postchallenge (dpc) compared to other groups with significant differences at all day of experiment and 21st dpv, 28th dpv, 7th dpc, and 14th dpc, respectively. The supplementation with Spirulina extract in G1 and G2 induced the highest hemagglutination inhibition antibody titer in a dose-dependent manner at all-time intervals. The antibody titer postvaccination was significantly increased in G1 and G2 at 14th, and 21st dpv, in comparison with G3. Furthermore, G1 and G2 showed higher significant antibody titers at 7th and 14th dpc, compared to other groups. Furthermore, Spirulina extract (200 and 400 mg/kg feed) in G1 and G2 showed anti-inflammatory effect in a dose dependant manner by downregulating nitric oxide levels at all times postchallenge with a significant difference at 3 to 7 dpc compared to G3, G4, and G6, with improved histopathological alterations in the trachea, lung, kidney, spleen, and bursa of Fabricius.  G6 supplied with 400 mg/kg Spirulina extract feed only without vaccination had a similar effect as vaccinated groups on innate immunity. However, it delayed the production of antibodies and did not prevent viral shedding as in vaccinated groups. In conclusion, vaccination in conjunction with either dose of Spirulina extract (G1, and G2) prevents viral shedding, increases the immune response, and reduces inflammation and histopathological change caused by H9N2 AI infection in a dose dependent manner. We recommend the use of 400 mg Spirulina extract/kg feed as a natural immunostimulant in conjunction with the H9N2 vaccine to achieve the highest possible level of protection against H9N2 AI infection.

Clover microgreen incorporation in diet-controlled diabetes and counteracted aflatoxicosis of rats.

Diabetes mellitus is one of the chronic metabolic diseases whose control remains a challenge. Its increased incidence was mainly attributed to increased environmental contamination. Therefore, this study aims to investigate the effect of feeding clover microgreen (CM) on a diabetes model with or without aflatoxin exposure. Rats were distributed into 8 groups. G1 was a control group. G2 was fed CM. G3 was administered aflatoxin orally. G4 was fed clover and administered aflatoxin. G5 was diabetic rats. G6 was diabetic rats fed CM. G7 was diabetic rats administered aflatoxin. G8 was diabetic rats administered aflatoxin and fed CM. Phytochemical analysis of the CM showed that gardenin was the most common compound. The administration of aflatoxin aggravated diabetes. The groups fed CM showed a decreased glucose concentration compared to the unfed groups. Liver and kidney function parameters were improved by CM. The histopathological alteration of the pancreas, liver, and kidneys was relieved in CM-fed groups. The area % of insulin in islets of Langerhans was increased in CM-fed groups. Feeding CM also enhanced the oxidative stress biomarkers. In conclusion, CM improved all evaluated parameters in diabetic rats either exposed to aflatoxin or not compared to the control.

Potential chemopreventive effects of Broccoli extract supplementation against 7, 12 dimethyl Benz(a)anthracene (DMBA) -induced toxicity in female rats.

Dietary components have recently received rapidly expanding attention for their potential to halt or reverse the development of many oxidative stress-mediated diseases after exposure to environmental toxicants. 7, 12 dimethylbenz(a)anthracene (DMBA) is one of the most common environmental pollutants. The present study aimed to evaluate the chemo-preventive effects of broccoli as a nutritional component against DMBA intoxication in rats. A daily dose of aqueous (1 ml/rat) and methanolic (150 mg/kg) broccoli extracts, respectively, was given to 50-day-old female rats for 26 successive weeks after carcinogen intoxication with a single dose of 20 mg/ml of DMBA. DMBA intoxication resulted in a redox imbalance (a decreased GSH level and an increased MDA level) and increased DNA fragmentation in the liver, kidney, and brain. Besides, it affected the level of expression of the bcl2 gene in the liver, kidney, and brain tissue but didn't affect cfos gene expression accompanied by histopathological changes. The aqueous and methanolic broccoli extract supplements ameliorated the adverse effects by increasing the level of GSH, decreasing the MDA level, and reducing DNA fragmentation. Besides, broccoli extracts decreased the expression of bcl2 in the liver and brain and up-regulated bcl2 expression in the kidney, accompanied by lowering NF-κß 65 expression in the liver and brain and γ-catenin expression in the liver and kidney. In conclusion, broccoli as a dietary component had a strong chemoprotective effect against oxidative stress, DNA damage, and genotoxicity induced by DMBA intoxication in rats.

Pathological and biochemical evaluation of radish microgreen on diabetes and aflatoxicosis in rats.

Diabetes mellitus type 2 remains one of the common diseases nowadays. Several risk factors can be implicated like increased environmental pollution. This study is aimed at evaluating the toxic effect of aflatoxin on diabetes mellitus and possible protection using natural food like radish microgreen (RM). Forty-eight male rats were randomly assigned to 8 groups: G1 control group, G2 RM group, G3 aflatoxin group, G4 aflatoxin-RM group, G5 diabetic group, G6 diabetic RM group, G7 diabetic-aflatoxin group, G8 diabetic, aflatoxin, RM group. Phytane and citronellyl tiglate were the main phytochemicals present in RM. The glucose and insulin levels were the worst in G5 and G7 groups. RM feeding restored glucose level to normal but did not alter insulin level. Insulin resistance was decreased, and insulin sensitivity was increased in groups fed RM. Liver and kidney function parameters and LDH activity were improved in groups fed RM. Histopathology of the pancreas and immunohistochemistry of insulin in pancreatic islets was improved in groups fed RM. In RM fed groups, the MDA content was decreased, whereas GSH content and antioxidant enzymes activity were increased. In conclusion, feeding RM in diabetic and/or aflatoxicated groups improved all evaluated parameters which could be due to its antioxidant potential.

Enhanced immune responses in dexamethasone immunosuppressed male rats supplemented with herbal extracts, chitosan nanoparticles, and their conjugates.

Nowadays, the world is challenged with highly contagious diseases, one of their preliminary virulence mechanisms is the suppression of innate immunity. Therefore, promoting natural immunity is a good precautionary strategy. we investigated and compared the effects of several natural herbal extracts -Moringa oleifera, Ziziphus spina christi, and Saussurea costus, and chitosan nanoparticles (CS NPs)- as well as conjugated extracts with CS NPs on the immunological parameters of dexamethasone immunosuppressed (IS) male rats. The plant extracts were assessed for total flavonoids, phenolics, and antioxidant activity. The CS NPs and their conjugates were characterized using particles size, zeta potentials, and Fourier-transform infrared spectroscopy analyses. The chemical analysis of the plant extracts, CS NPs, and their conjugates was performed using energy dispersive X-ray fluorescence, and their cytotoxicity was evaluated in human lung fibroblast (WI-38) and human embryonic kidney (HEK-293) cell lines. For in vivo evaluations, 72 adult male rats were divided into 9 groups: control, IS, three plant extracts, CS, and conjugates of the three plant extracts and CS NPs. Oral supplementation (day after day) lasted for 28 days. Liver, kidney, and spleen tissue samples were collected for histopathology and Ki-67 expression analyses. The results revealed that the plant extracts and CS improved the total leukocyte counts, complement 3, complement 4, interferon-gamma, and tumor necrosis factor levels at day 28. However, the plant extract-CS NPs conjugates faster and have higher immunostimulatory effects at day 14. Furthermore, the atrophied white pulp of the spleen induced by dexamethasone was alleviated, and Ki-67 expression was elevated in all the treated groups. Conclusively, the conjugates of Moringa oleifera, Ziziphus spina christi, and Saussurea costus extract with CS NPs demonstrated more potent and rapid immune responses at lower doses and concentrations compared to the plant extracts or CS NPs alone, without causing liver or kidney injuries. Thus, supplementation of these conjugated plant extracts at lower doses and concentrations is recommended to improve immunity while considering safety considerations.

Neem leaf powder (Azadirachta indica) mitigates oxidative stress and pathological alterations triggered by lead toxicity in Nile tilapia (Oreochromis niloticus).

This study investigated the clinical and pathological symptoms of waterborne lead toxicity in wild Nile tilapia collected from a lead-contaminated area (the Mariotteya Canal: Pb = 0.6 ± 0.21 mg L-1) and a farmed fish after 2 weeks of experimental exposure to lead acetate (5-10 mg L-1) in addition to evaluating the efficacy of neem leaf powder (NLP) treatment in mitigating symptoms of lead toxicity. A total of 150 fish (20 ± 2 g) were alienated into five groups (30 fish/group with three replicates). G1 was assigned as a negative control without any treatments. Groups (2-5) were exposed to lead acetate for 2 weeks at a concentration of 5 mg L-1 (G2 and G3) or 10 mg L-1 (G4 and G5). During the lead exposure period, all groups were reared under the same conditions, while G3 and G5 were treated with 1 g L-1 NLP. Lead toxicity induced DNA fragmentation and lipid peroxidation and decreased the level of glutathione and expression of heme synthesis enzyme delta aminolaevulinic acid dehydratase (ALA-D) in wild tilapia, G2, and G4. NLP could alleviate the oxidative stress stimulated by lead in G3 and showed an insignificant effect in G5. The pathological findings, including epithelial hyperplasia in the gills, edema in the gills and muscles, degeneration and necrosis in the liver and muscle, and leukocytic infiltration in all organs, were directly correlated with lead concentration. Thus, the aqueous application of NLP at 1 g L-1 reduced oxidative stress and lowered the pathological alterations induced by lead toxicity.

Ceratonia siliqua pods (Carob) methanol extract alleviates doxorubicin-induced nephrotoxicity via antioxidant, anti-inflammatory and anti-apoptotic pathways in rats.

Doxorubicin (DOX) is an anti-neoplastic therapy, but its use is limited by its deleterious toxic effects including nephrotoxicity and cardiotoxicity. This work aimed at assessing the potential protective effect of Ceratonia siliqua methanol extract (CME) on DOX-induced nephrotoxicity in 5 groups of Wistar rats. Nephrotoxicity was induced experimentally by intraperitoneal (IP) injection of DOX (15 mg/kg). DOX increased serum creatinine, urea, sodium, and potassium levels. It elevated MDA levels in the renal tissue but decreased the concentration of GSH and the activity of GST, CAT, and SOD. Meanwhile, it decreased the level of immunomodulatory anti-inflammatory mediators: IL-10 and TGF-ß, as well as the activity of MPO but increased the level of IL-6, TNF-α, and caspase-3 in the renal tissue. DOX has upregulated COX-2, caspase-9, and Bax gene expression and downregulated the Bcl-2 gene expression. Immunolabeling of renal tubular epithelium in DOX-intoxicated rats was moderate to strong against Bax, COX-2, and NF-kß and weak against Bcl-2. Treatment with CME significantly restored the levels of kidney function parameters and the levels of oxidative stress markers. It stimulated the production of IL-10 and TGF-ß and decreased the level of IL-6 and TNF-α. CME reverted the gene expression of COX-2, caspase-9, and Bax. Microscopically, CME alleviated the DOX-induced renal damage. Phytochemical analysis revealed the presence of 26 compounds in the CME. No signs of acute toxicity were recorded by CME up to 4000 mg/kg b. wt. orally into mice. Finally, CME could effectively alleviate the deleterious effects of DOX on the kidney. The safety of carob extract encourages its use in the preparation of valuable therapeutic agents.

Promising effect of Geranium robertianum L. leaves and Aloe vera gel powder on Aspirin®-induced gastric ulcers in Wistar rats: anxiolytic behavioural effect, antioxidant activity, and protective pathways.

BACKGROUND: Many drugs have been restricted in the treatment of gastric ulcers (GU). So, herbal medicines are now in great demand for their better cultural acceptability, compatibility, and minimal side effects. Therefore, our study aimed to assess the protective efficacy of Aloe vera gel and Geranium robertianum extracts against Aspirin®-induced GU in Wistar rats. METHODS: Antioxidant activity and chemical composition of both herbs were analysed. Then, we divided forty female Wistar rats into five groups: a negative control group, a positive control group of Aspirin®-induced GU, and pretreated groups with Aloe Vera, geranium, and Famotidine (reference drug). The locomotor disability, anxiety-like behaviour, and ultrasonography were assessed. Ultimately, scarification of animals to determine gastric juice pH and ulcer index. Then the collection of stomach and liver for histopathological and immunohistochemical examinations, besides tracing the oxidative stress biomarkers and related genes. RESULTS: High content of polyphenols was revealed in both extracts. The pretreatment with Aloe vera gel and geranium showed significant antioxidant activities with free radical scavenging and ferric-reducing power (FRAP). Moreover, they improved the stomach architecture and alleviated anxiety-like behaviour and motor deficits. They significantly reduced the expression of proinflammatory cytokine (TNF-α), inflammatory, and oxidative stress genes (NF-KB, HO-1, Nrf-2) while increasing the Keap-1 in gastric mucosa. CONCLUSION: Data presented a significant protective effect of Aloe vera gel and geranium against Aspirin®-induced GU; they reduced gastric mucosal injury with potential anxiolytic effects through their anti-inflammatory and antioxidant properties. Therefore, they may be considered promising agents for preventing or treating gastric ulceration.

Histopathological, biochemical and molecular studies on a model of systemic autoimmune disease induced by sodium silicate in non-genetically prone rats.

Sodium silicate (Na2SiO3) is an inorganic silica salt used in many products. Few studies reported autoimmune diseases (AIDs) due to Na2SiO3 exposure. This study investigates the role of Na2SiO3 exposure by different routes and doses in AID development in rats. We assigned 40 female rats to four groups: G1 control group, G2 rats were subcutaneously injected with 5 mg Na2SiO3 suspension, and G3 and G4 rats were orally administered 5 mg and 7 mg Na2SiO3 suspension, respectively. Na2SiO3 was administered weekly for 20 weeks. Serum anti-nuclear antibodies (ANA) detection, histopathology of kidney, brain, lung, liver, and heart, oxidative stress biomarkers (MDA and GSH) in tissues, Matrix metalloproteinase activity in serum, TNF-α, and Bcl-2 expression in tissues were performed. ANA was significantly increased in silicate groups, especially G2. Creatinine was significantly increased in silicate groups. Histopathology revealed vasculitis and fibrinoid degeneration of blood vessels, a picture of immune-mediated glomerulonephritis in the kidneys, and chronic interstitial pneumonia with medial hypertrophy of pulmonary blood vessels. The activity of gelatinases (MMP-2 and MMP-9) and collagenase (MMP-13), which play role in inflammation, remodeling, and immune complex degradation, were significantly increased in the silicate-exposed groups. Bcl-2 was significantly decreased, indicating apoptosis. Therefore, oral administration and subcutaneous injection of Na2SiO3 induced immune-mediated glomerulonephritis with elevated ANA levels and overexpression of TNF-α in rats.

Performance and nutrigenomics modulations in response to the inclusion of biologically treated date-palm mulch and enzyme mixture in the diets of growing rabbits.

This study was conducted to evaluate the effects of Allzyme addition on biologically-treated date-palm mulch (DPM) based diets for growing rabbits. DPM was treated by Trichoderma viride, Trichoderma reesi 230, Plorotus oysterous, and Phanaerochyte chrysosporium. Eighty rabbits were assigned to four groups: a control group, tDPM (10% tDPM inclusion of total diet), Allzyme (Allzyme supplementation), and tDPM + Allzyme (tDPM and Allzyme supplementation). The biological treatment resulted in a significant increase in crude protein and reductions in crude fiber. There was an interaction between tDPM and Allzyme at 9- and 10-week BW. The negative effects of tDPM on BW started at 8-week of age. The tDPM had unfavorable effects on slaughter and meat quality traits. The tDPM-by-Allzyme interaction affected total protein and globulin concentrations. However, blood glucose concentration was influenced by both tDPM and Allzyme. A significant tDPM effect was detected on the expression of INSR, GHSR, and IGF1 genes. However, the Allzyme effect was significant for PPARg and FASN genes. In conclusion, feeding tDPM negatively impacted rabbit's performance, however, Allzyme supplementation alleviated some of those effects. Accordingly, tDPM is recommended to be included in the diets of growing rabbits along with Allzyme supplementation.

Hordeum vulgare L. microgreen mitigates reproductive dysfunction and oxidative stress in streptozotocin-induced diabetes and aflatoxicosis in male rats.

Diabetes mellitus type 2 (DM) is a common chronic disease worldwide, which may be due to increased environmental pollution. Aflatoxin B1 is a likely inevitable contaminant in food and dairy products. Both DM and aflatoxicosis exert a deleterious effect on reproduction urging the exploration of various functional food for protection. This study investigated the effect of barley microgreen (BM) on reproductive disorders caused by DM with or without aflatoxicosis in male rats. Rats were divided into eight groups; G1 control, G2 barley, G3 aflatoxin, G4 aflatoxin-barley, G5 streptozotocin (STZ), G6 STZ-barley, G7 STZ-aflatoxin, and G8 STZ-aflatoxin-barley. BM chemical composition revealed elevated calcium, iron, phosphorus, and vitamin A compared with barely seeds. Complete blood picture, lipid profile, serum oxidative stress parameters, relative testicular weight, sperm analysis, chromosomal aberration, and testis histopathology were performed. The lipid profile was altered significantly in G7. Oxidative stress was increased in G3, G5, and G7, whereas it was decreased in BM-treated groups. Sperm counts were reduced significantly in aflatoxin and/or STZ groups but increased significantly in BM-treated groups. Sperm morphological abnormalities and chromosomal aberrations were decreased significantly in BM-treated groups compared with untreated groups. Testicular histopathology revealed moderate diffuse degeneration of seminiferous tubules in aflatoxin and/or STZ groups, which were alleviated in BM-treated groups. In conclusion, aflatoxin and STZ together caused severe reproductive disorder and oxidative stress more than aflatoxin or STZ alone. BM diet reduced significantly oxidative stress and reproductive disorder associated with DM and aflatoxicosis in rats.

The anti-inflammatory effect of myrrh ethanolic extract in comparison with prednisolone on an autoimmune disease rat model induced by silicate.

Autoimmune disease is a complex chronic disease that triggers immune activation against autoantigens resulting in tissue damage. Epidemiological data showed that autoimmune diseases are increasing worldwide over the last decades owing to increased environmental pollution. This study investigates the therapeutic effect of myrrh as a natural medicine compared to prednisolone in the treatment of immune-mediated glomerulonephritis induced by silicate. The autoimmune disease model in rats was induced by injecting 5 mg crystalline sodium silicate suspension subcutaneously once weekly for 20 weeks, and then the rats were treated either with myrrh extract or prednisolone or with both for 6 weeks. Liver and kidney function tests, histopathology, and immunohistochemistry of TNF-α expression in kidney tissue were performed. The creatinine significantly elevated in silica-treated group and decreased in other treated groups. Histopathology of the kidney revealed improvement of glomerular and tubular basement thickness in all treated groups, but the inflammatory cell count slightly decreased in the group treated with myrrh than the other treated groups which showed a marked decrease. TNF-α expression was significantly decreased in all treated groups. Interestingly, the myrrh did not produce hepatic lesions and improve the side effect of prednisolone in the liver when taken in combination. Therefore, myrrh extract possessed anti-inflammatory properties and counteracted the side effect of prednisolone on the liver. Myrrh extract can serve as a conjunctive therapy with prednisolone to treat autoimmune diseases.

The therapeutic potential of Camel Wharton jelly mesenchymal stem cells (CWJ-MSCs) in canine chronic kidney disease model.

BACKGROUND: Chronic kidney disease (CKD) is a worldwide health problem that its incidence increases nowadays with the increase in the risk of environmental pollution. CKD can progress to end-stage renal disease (ESRD) which usually ends fatally. This study aimed to examine the therapeutic potential of Camel Wharton jelly-mesenchymal stem cells (CWJ-MSCs) in chronic kidney disease model induced in dogs. METHODS: CWJ-MSCs were injected directed to the kidney with ultrasonographic guidance in dogs with 5/6 nephrectomy to evaluate its therapeutic potency in such cases. Analysis of variance was applied in normally distributed quantitative variables while a non-parametric Mann-Whitney test was used for non-normally distributed quantitative variables. RESULTS: The serum urea and creatinine in the treated group were significantly decreased transferring dogs in the treated group from stage 3 to stage 2 CKD according to the IRIS staging system. Histopathology of renal tissue revealed improving CKD lesions by increasing regeneration of degenerated tubules, maintaining the integrity of glomeruli. New vascularization with blood vessels remodeling were common findings. Periodic acid Schiff stain of renal tissue showed the integrity of renal tubules and thickness of the glomerular basement membrane. Fibrosis of cortex and medulla was lower in the treated group than in the CKD model as monitored by Mallory's trichrome stain (MTC). NGAL and KIM-1 genes expression were decreased while VEGF and EGF genes expression were increased indicating renal tissue repair. CONCLUSIONS: CWJ-MSCs have a therapeutic potential in the CKD model induced in dogs.