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

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

Correction: Ammar et al. Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses. Nutrients 2022, 14, 841.

In the original publication [...].

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

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

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

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

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

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

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

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

Metabolomics approach of Symphyotrichum squamatum ethanol extract and its nano-Ag formulation protective effect on gastric ulcer via bio-chemical and pathological analyses.

ContextGastric ulcer (GU) a widely distributed ailment is associated with many causes, including alcohol consumption.Materials and MethodsChemical profiling of Symphyotrichum squamatum ethanol extract (SSEE) was established via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) and employed in a silver nano-formulation (SSEE-N-Ag). SSEE and SSEE-N-Ag antiulcer activities were estimated against ethanol-induced rats by biochemical, histological, and metabolomics assessments. Reduced glutathione, total antioxidant capacity and prostaglandin E2 levels and gastric mucosa histopathological examination were analysed. The rats' metabolome changing alongside action pathways were elucidated via metabolite profile coupled to multivariate data analysis.ResultsUPLC-MS profiling of SSEE identified 75 components belonging to various classes. Compared with control, EtOH-treated rats showed decreased of tissue GSH, TAC and PGE2 by 62.32%, 51.85% and 47.03% respectively. SSEE and SSEE-N-Ag administration mitigated biochemical and histopathological alterations. Serum metabolomics analysis revealed for changes in several low molecular weight metabolites with ulcer development. These metabolites levels were restored to normal post-administration of SSEE-N-Ag. SSEE-N-Ag as mediated via modulating numerous metabolic pathways such as lipids, pyrimidine, energy metabolism and phosphatidylinositol signalling. This study provides novel insight for metabolic mechanisms underlying gastric ulcer relieving effect.ConclusionPresent results revealed potential antiulcer effect of SSEE and SSEE-N-Ag by decreasing ulcer-associated syndromes, supporting their anti-ulcerogenic action.

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats.

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF-MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract's effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF-MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress.

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

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

Osteogenic enhancement of modular ceramic nanocomposites impregnated with human dental pulp stem cells: an approach for bone repair and regenerative medicine.

BACKGROUND/AIM: Human dental pulp-derived mesenchymal stem cells (hDP-MSCs) are a promising source of progenitor cells for bone tissue engineering. Nanocomposites made of calcium phosphate especially hydroxyapatite (HA) offer an impressive solution for orthopedic and dental implants. The combination of hDP-MSCs and ceramic nanocomposites has a promising therapeutic potential in regenerative medicine. Despite the calcium phosphate hydroxyapatite (HA)-based nanocomposites offer a good solution for orthopedic and dental implants, the heavy load-bearing clinical applications require higher mechanical strength, which is not of the HA' properties that have low mechanical strength. Herein, the outcomes of using fabricated ceramic nanocomposites of hydroxyapatite/titania/calcium silicate mixed at different ratios (C1, C2, and C3) and impregnated with hDP-MSCs both in in vitro cultures and rabbit model of induced tibial bone defect were investigated. Our aim is to find out a new approach that would largely enhance the osteogenic differentiation of hDP-MSCs and has a therapeutic potential in bone regeneration. SUBJECTS AND METHODS: Human DP-MSCs were isolated from the dental pulp of the third molar and cultured in vitro. Alizarin Red staining was performed at different time points to assess the osteogenic differentiation. Flow cytometer was used to quantify the expression of hDP-MSCs unique surface markers. Rabbits were used as animal models to evaluate the therapeutic potential of osteogenically differentiated hDP-MSCs impregnated with ceramic nanocomposites of hydroxyapatite/tatiana/calcium silicate (C1, C2, and C3). Histopathological examination and scanning electron microscopy (SEM) were performed to evaluate bone healing potential in the rabbit induced tibial defects three weeks post-transplantation. RESULTS: The hDP-MSCs showed high proliferative and osteogenic potential in vitro culture. Their osteogenic differentiation was accelerated by the ceramic nanocomposites' scaffold and revealed bone defect's healing in transplanted rabbit groups compared to control groups. Histopathological and SEM analysis of the transplanted hDP-MSCs/ceramic nanocomposites showed the formation of new bone filling in the defect area 3 weeks post-implantation. Accelerate osseointegration and enhancement of the bone-bonding ability of the prepared nanocomposites were also confirmed by SEM. CONCLUSIONS: The results strongly suggested that ceramic nanocomposites of hydroxyapatite/ titania /calcium silicate (C1, C2, and C3) associated with hDP-MSCs have a therapeutic potential in bone healing in a rabbit model. Hence, the combined osteogenic system presented here is recommended for application in bone tissue engineering and regenerative medicine.

Renoprotective and Cardioprotective Potential of Moricandia sinaica (Boiss.) against Carbon Tetrachloride-Induced Toxicity in Rats.

The goal of the current study was to assess the nephroprotective and cardioprotective potential of Moricandia sinaica methanol extract (MOR-1), as well as its butanol (MOR-2) and aqueous (MOR-3) fractions against carbon tetrachloride (CCl4)-induced nephro and cardio-toxicity. Cardiac function was assessed using the biochemical parameters lactate dehydrogenase (LDH) and creatinine kinase (CK). Renal function was examined using the biochemical parameters creatinine and uric acid. The levels of nonprotein sulfhydryls (NPSH) and malondialdehyde (MDA) were used as markers of oxidative strain. A dose of 100 and 200 mg/kg of butanol fraction given prior to CCl4 treatment significantly (p < 0.05 - 0.001) protected against elevated LDH and CK levels. Similarly, treatment with silymarin (10 mg/kg) and butanol fraction (100 and 200 mg/kg) significantly (p < 0.05 - 0.001) boosted total protein levels compared to CCl4 treatment alone. The silymarin (10 mg/kg) and butanol fraction (100 and 200 mg/kg) also provided a significant (p < 0.05 - 0.001) protective effect for MDA levels. Methanol extract (MOR-1) and butanol (MOR-2) showed significant results and were recommended for further pharmacological and screening for active constituents.

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

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

Histomorphological Changes in a Rat Model of Polycystic Ovary Syndrome and the Contribution of Stevia Leaf Extract in Modulating the Ovarian Fibrosis, VEGF, and TGF-ß Immunoexpressions: Comparison with Metformin.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of fertile females. It has been reported that stevia leaf extract (SLE) has antidiabetic and antihyperlipidemic properties. Therefore, the current study hypothesized and investigated the role and mechanistic aspects of a natural sweetener; SLE in treating a rat model of letrozole-induced PCOS and to compare it with metformin. Thirty-five female Wistar albino rats were divided into 5 groups: control, PCOS-induced group (letrozole, 1 mg/kg/d, for 21 days), SLE, metformin, and combination-treated groups (300 mg/kg/d, for the next 28 days in SLE and metformin-treated groups). Vaginal smears were done. The levels of glucose, lipid, and hormonal profiles were measured in the serum meanwhile, malonyl dialdehyde (MDA), superoxide dismutase (SOD), and tumour necrosis factor (TNF-α) were measured in the ovary. Ovarian sections were subjected to hematoxylin and eosin, Masson, and immunohistochemical identification of VEGF and TGF-ß followed by morphometric analysis. PCOS rats showed altered hormonal and lipid profiles, in addition to hyperglycemia. Also, the ovarian tissue levels of MDA and TNF-α were elevated, and SOD was decreased. Numerous cystic follicles, decrease/absence of corpora lutea, interstitial fibrosis with positive VEGF and TGF-ß immunoreactivity were evident. SLE improved all altered parameters. SLE showed potential therapeutic merits in letrozole-induced PCOS via anti-inflammatory, antioxidant, anti-fibrotic, and angiogenesis regulating mechanisms. Its effects were almost comparable to metformin, and the combination of both has no further synergistic effect.

Cytoprotective potentialities of carvacrol and its nanoemulsion against cisplatin-induced nephrotoxicity in rats: development of nano-encasulation form.

Cisplatin (Cisp) is a widely distributed chemotherapeutic drug for cancers. Nephrotoxicity is one of the most common side effects of the use of this drug. Carvacrol (CV) is a common natural compound in essential oils and extracts of medicinal plants with potent in vivo and in vitro bioactivities. The work was extended to achieve the target of investigation of the protective potentialities of CV and its nanoemulsion as a cytoprotective drug against Cisp-induced nephrotoxicity in albino rats. CV-nanoemulsion was prepared by a hydrophilic surfactant polysorbate 80 (Tween 80) and deionized water. The TEM image of the particle distribution prepared nanoemulsion is mainly spherical in shape with particle size varying between 14 and 30 nm. Additionally, the Cisp administration caused the increasing of the levels of urea and creatinine in the blood and serum. These increasing of urea and creatinine levels caused consequently the turbulence of the oxidative stress as well as the rising of hs-CRP, IL-6, and TNF-α levels in the serum. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with CV-nanoemulsion. Expression levels of nephrotoxicity-related genes including LGALS3, VEGF, and CAV1 in kidney tissue using qRT-PCR were measured. The results revealed that the expression of LGALS3, VEGF and CAV1 genes was highly significantly increased in only Cisp treated group when compared with other treated groups. While, these genes expressions were significantly decreased in Cisp + CV treated group when compared with Cisp treated rats (P < 0.001). In addition, there were no significant differences between Cisp + nano-CV treated group and both negative control and nanoemulsion alone groups but it was not significant. In addition, the Western blot of protein analysis results showed that the LGALS3 and CAV1 are highly expressed only in Cisp + CV treated group compared with other groups. There was no significant difference between Cisp + nano-CV treated animals and negative control for both mRNA and protein expression. Based on these results, CV was combined with calcium alginate; a more stable capsule is formed, allowing for the formation of a double wall in the microcapsule. These results supported the therapeutic effect of CV and its nano-emulsion as cytoprotective agents against Cisp nephrotoxicity.

Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses.

Citrus fruits are grown worldwide for their special nutritive and several health benefits. Among citrus bioactives, naringenin, a major flavanone, exhibits a potential hepatoprotective effect that is not fully elucidated. Herein, serum biochemical parameters and histopathological assays were used to estimate the hepatoprotective activity of naringenin, isolated from Citrus sinensis (var. Valencia) peels, in CCl4-induced injury in a rat model. Further, GC-MS-based untargeted metabolomics was used to characterize the potential metabolite biomarkers associated with its activity. Present results revealed that naringenin could ameliorate the increases in liver enzymes (ALT and AST) induced by CCl4 and attenuate the pathological changes in liver tissue. Naringenin decreased urea, creatinine and uric acid levels and improved the kidney tissue architecture, suggesting its role in treating renal disorders. In addition, naringenin increased the expression of the antiapoptoic cell marker, Bcl-2. Significant changes in serum metabolic profiling were noticed in the naringenin-treated group compared to the CCl4 group, exemplified by increases in palmitic acid, stearic acid, myristic acid and lauric acids and decrease levels of alanine, tryptophan, lactic acid, glucosamine and glucose in CCl4 model rats. The results suggested that naringenin's potential hepato- and renoprotective effects could be related to its ability to regulate fatty acids (FAs), amino acids and energy metabolism, which may become effective targets for liver and kidney toxicity management. In conclusion, the current study presents new insights into the hepato- and renoprotective mechanisms of naringenin against CCl4-induced toxicity.

Gastro-protective effect of Artemisia Sieberi essential oil against ethanol-induced ulcer in rats as revealed via biochemical, histopathological and metabolomics analysis.

CONTEXT: Gastric ulcer is regarded as one of the main clinical ailments with high morbidity and mortality rates. MATERIALS AND METHODS: Gastro-protective effect of Artemisia sieberi essential oil (AS-EO) in ethanol-induced rats was evaluated via biochemical, histopathological and large-scale metabolomics analyses. Glutathione (GSH), total antioxidant capacity (TAC), prostaglandin (PGE2) and tumour necrosis factor α (TNF-α) alongside with histopathological examination of gastric mucosa were analysed. Metabolites profiling coupled to Global Natural Products Social molecular networking platform (GNPS) and multivariate data analyses to reveal for changes in rats metabolome with treatments and involved action mechanisms. RESULTS: Pre-treatment with 100 and 200 mg/kg of AS-EO in EtOH-treated rats restored all parameters towards normal status compared to disease model. AS-EO alleviated the histological and pathological damage of gastric tissue caused by ethanol. Metabolites profiling revealed an increase in uracil, cholesterol and fatty acids/fatty acyl amides levels in ulcer rats and restored to normal levels post AS-EO intervention. These results indicated the efficacy of AS-EO in a dose-dependent manner, and to exert protective effects in ulcer rat model by targeting several metabolic pathways viz. lipid, energy, and nucleotide metabolisms. CONCLUSION: AS-EO adds to the known uses of genus Artemisia as anti-ulcerogenic agent by attenuating oxidative stress and inflammatory responses associated with an ulcer. Several novel biomarkers for ulcer progression in rats were identified and have yet to be confirmed in human models.

1,8 Cineole and Ellagic acid inhibit hepatocarcinogenesis via upregulation of MiR-122 and suppression of TGF-ß1, FSCN1, Vimentin, VEGF, and MMP-9.

Hepatocellular carcinoma (HCC) is one of the most burdened tumors worldwide, with a complex and multifactorial pathogenesis. Current treatment approaches involve different molecular targets. Phytochemicals have shown considerable promise in the prevention and treatment of HCC. We investigated the efficacy of two natural components, 1,8 cineole (Cin) and ellagic acid (EA), against diethylnitrosamine/2-acetylaminofluorene (DEN/2-AAF) induced HCC in rats. DEN/2-AAF showed deterioration of hepatic cells with an impaired functional capacity of the liver. In addition, the levels of tumor markers including alpha-fetoprotein, arginase-1, alpha-L-fucosidase, and ferritin were significantly increased, whereas the hepatic miR-122 level was significantly decreased in induced-HCC rats. Interestingly, treatment with Cin (100mg/kg) and EA (60mg/kg) powerfully restored these biochemical alterations. Moreover, Cin and EA treatment exhibited significant downregulation in transforming growth factor beta-1 (TGF-ß1), Fascin-1 (FSCN1), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and epithelial-mesenchymal transition (EMT) key marker, vimentin, along with a restoration of histopathological findings compared to HCC group. Such effects were comparable to Doxorubicin (DOX) (2mg/kg); however, a little additive effect was evident through combining these phytochemicals with DOX. Altogether, this study highlighted 1,8 cineole and ellagic acid for the first time as promising phytochemicals for the treatment of hepatocarcinogenesis via regulating multiple targets.

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

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

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

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