Evaluating the role of polysaccharide extracted from Pleurotus columbinus on cisplatin-induced oxidative renal injury.

This research aimed to examine the antioxidant polysaccharide activity (PsPc-3) derived from Pleurotus columbinus (P. columbinus) on oxidative renal injury (ORI) induced by cisplatin (CP). The principal components of crude polysaccharide were assessed. We studied the preventive impact of polysaccharide on cisplatin-induced renal damage in this study. For 21 days, we employed the CP-induced ORI rat model and divided the rats into four groups: control, CP alone, polysaccharide post CP (100 mg/kg) orally, and CP + polysaccharide (pre and post). The chemical characterization of the polysaccharide fraction PsPc-3 stated that protein was not present. PsPc-3 contained 7.2% uronic acid as assessed as 0% sulfate. PsPc-3 hydrolysate structured of Galacturonic:Glucose:Xylose and their molar proportions were 1:4:5, respectively. The average molecular weight (Mw) and molecular mass (Mn) per molecule of PsPc-3 were 5.49 × 104 g/mol and Mn of 4.95 × 104 g/mol respectively. DPPH radical scavenging activity was demonstrated by the polysaccharide of 65.21-95.51% at 10 mg/ml with IC50 less than 10 mg/ml. CP increased serum urea to 92.0 mg/dl and creatinine up to 1.0 mg/dl, with a concurrent decrease in the levels of total protein to 4.0 mg/dl. Besides, Also, CP-induced ORI raised levels of malondialdehyde (MDA), alkaline phosphatase (ALP), and renal hormones (renin and aldosterone), with a decline in antioxidants compared to control rats. In addition, in the presence of CP, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels increased. PsPc-3 decreased these changes dramatically. PsPc-3 improves pathological renal damage caused by CP and decreases tubular apoptosis measured by DNA ladder formation and cleaved caspase- 3. These findings showed that PsPc-3 isolated from P. columbinus protects and inhibits tubular apoptosis in cisplatin-induced ORI. Furthermore, PsPc-3 has no influence on the anticancer efficacy of CP in rats. Thus, PsPc-3 derived from P. columbinus might provide a novel therapy method for cisplatin-induced nephrotoxicity.

Evaluating the role of propolis and bee venom on the oxidative stress induced by gamma rays in rats.

Honeybee products consist of many substances, which have long been known for their medicinal and health-promoting properties. This study set out to appraise the protective potential of Egyptian propolis (EP) and bee venom (BV) separately or combined against total body irradiation (TBI) induced oxidative injury in rats. Besides, we assessed the bioactive components in EP and BV using HPLC and UPLC/ ESI-MS analysis in the positive ion mode. The animals were subjected to a source of gamma ionizing radiation at a dose of 6 Gy. Propolis and BV were administered independently and in combination before 14 days of γ-irradiation. Liver and kidney functions were estimated besides, DNA damage index (8- OHdG) by ELISA. Antioxidants, including glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were detected. Gene expression technique investigated for BAX, BCL2, and in plasma also miR125b expression in serum of rats. Besides, the histopathological for the brain, liver, kidney, and heart were investigated. In addition, lipid peroxidation was investigated in plasma and in the previous organs. The present results provide opportunities to advance the use of bee products as promising medicinal sources.

Effects of Sargassum virgatum extracts on the testicular measurements, genomic DNA and antioxidant enzymes in irradiated rats.

BACKGROUND: Oxidative stress and reactive oxygen species (ROS) are primarily responsible for the development of male infertility after exposure to γ-irradiation. The present work aimed to assess the ameliorative and therapeutic roles of the aqueous and ethanolic extracts of the edible seaweed Sargassum virgatum (S. virgatum) on spermatogenesis and infertility in γ-irradiated Wistar rats. MATERIALS AND METHODS: Induction of infertility was performed by exposing the rats to 137Cs-gamma rays, using a single dose of 3.5 Gy. γ-irradiated rats were given the S. virgatum ethanolic (S. virgatum-EtOH) and aqueous extracts intraperitoneally on a daily base for two consecutive weeks at doses of 100 and 400 mg/kg body weight (b.wt.) for each seaweed extract. Morphometric data of the testes, semen quality indices, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx), and deoxyribonucleic acid (DNA) fragmentation were assessed. The results obtained were taken during two-time intervals of 15 and 60 days from the commencement of the algal treatments. In vitro antioxidant assays and polyphenolic compounds of S. virgatum were characterized. RESULTS: Significant negative changes in the semen quality and morphometric data of the testes, as well as remarkable DNA fragmentation, were detected in the irradiated rats compared to the control. The levels of the endogenous antioxidant enzymes (SOD, CAT, GSH, and GPx) were also significantly diminished. Nonetheless, treatments of γ-irradiated rats with the S. virgatum-EtOH and aqueous extracts significantly improved the above-mentioned enzymes, in addition to noteworthy amendments in the dimensions of the testes, the semen quality, as well as the DNA structure. CONCLUSIONS: The ameliorative potency of S. virgatum to cure γ-irradiation-induced male infertility, particularly 400 mg/kg ethanolic extract for 60 days, is the result of the consistent therapeutic interventions of its potent antioxidant and anti-apoptotic polyphenols, particularly protocatechuic, p-hydroxybenzoic, rosmarinic, chlorogenic, cinnamic and gentisic acids, as well as the flavonoids catechin, hesperidin, rutin and quercetin. Besides its high-value nutraceutical importance, S. virgatum could be a natural candidate for developing well-accepted radioprotectant products capable of treating γ-irradiation-induced male infertility.

Assessment role of total phenols and flavonoids extracted from Pleurotus columbinus mushroom on the premature ovarian failure induced by chemotherapy in rats.

BACKGROUND: Many species of mushroom contain an assortment of free radical scavengers (Phenolics and Flavonoids compounds) that have made them nutritionally beneficial and a source of expansion of drug production. In this study, we examined the preventive and remedial role of total phenol extract from Pleurotus columbines (TP) in alleviating the consequences of cyclophosphamide (CTX) on the ovaries of female rats. Rats were randomly assigned to four groups: healthy controls, cyclophosphamide (CTX), received a TP (100 mg/kg) orally daily for 14 days and curative group: CTX-TP, we determined and identified a total phenol from a mushroom extract and examined it as an antioxidant agent. To investigate the therapeutic influence, it was administrated 2 weeks after CTX. To assess the impact of TP on ovarian damage caused by CTX, ovarian hormone tests were performed such as luteinizing hormone (LH), 17-ß-estradiol (E2), and anti-mullerian hormone (AMH). Besides, follicle-stimulating hormone (FSH) in serum was evaluated, and histopathological analysis of the ovary was examined. RESULTS: This study indicates that treatment with TP decreased the severity of cyclophosphamide-induced ovary injury by reducing inflammation and apoptotic effects and increasing the activity of antioxidants. CONCLUSIONS: TP could be used to alleviate cyclophosphamide-induced ovary injury.

Effects of silver nanoparticles-polysaccharide on bleomycin-induced pulmonary fibrosis in rats.

OBJECTIVES: The first goal of this study was to synthesize the silver nanoparticles Alcaligenes xylosoxidans exopolysaccharide (Ag-AXEPS). The second objective was to analyse the role of Ag-AXEPS nanoparticles (NPS) in treating bleomycin (BLM)-induced lung fibrosis. METHODS: Intratracheal bleomycin (2.5 U/kg) was administered to prompt pulmonary fibrosis in rats, and pulmonary fibrosis was treated with Ag-AXEPS nanoparticles (100 ppm/twice a week for four weeks). KEY FINDINGS: Ag-AXEPS nanoparticles significantly decreased the diversity of pulmonary inflammatory agents in rats with BLM-induced fibrosis. Reduced levels of respiratory tumor necrosis factor-alpha, monocyte chemotactic protein-1, matrix metalloproteinases (MMP-2 and MMP-9) were observed on treatment with synthesized Ag-AXEPS. Similarly, the treatment decreased IL-12, mRNA levels of BAX and plasma fibrosis markers like N-terminal procollagen III propeptide and transforming growth factor-ß1. On the other hand, the treatment increased mRNA BCL2 and total antioxidant capacity. It also lowered the level of fibrosis, as was shown by a quantified pathologic study of hematoxylin-eosin-stained lung parts. The treatment, however, ensured that lung collagen was restored, as assessed by Masson's trichrome stain, and that overall survival was increased and enhanced. CONCLUSIONS: Our work showed that nanoparticles could be obtained at 37°C and may be a possible pulmonary fibrosis therapeutic agent.

Study of the chemical structure of exopolysaccharide produced from streptomycete and its effect as an attenuate for antineoplastic drug 5-fluorouracil that induced gastrointestinal toxicity in rats.

Chemotherapeutic medications, including 5 - fluorouracil (5FU), are the same old technique to most cancers and are associated with numerous peripheral toxicities. We investigated exopolysaccharide (EPSST) produced from the isolated streptomycete of the Mediterranean Sea for the capability to lower the severity of mucositis in vivo. The streptomycete was isolated from Mediterranean Sea sediment from the beaches of Port Said Governorates, Egypt and identified morphologically, physiologically, and biochemically and confirmed by molecularly 16S rDNA analysis. The EPSST was extracted from the supernatant of streptomycete by using 4 volumes chilled ethanol and then the functional groups, MW, and chemical evaluation have been detected via Fourier-transform infrared (FTIR), and high-performance liquid chromatography (HPLC). In addition, antioxidant activity was measured through the usage of 2, 2-diphenyl-1-picrylhydrazyl (DPPH). Thirty-two male rats (180-200 g) were randomly divided into a control group (normal saline), intraperitoneal injection of 5-fluorouracil (5-FU, 150 mg/kg), normal rats were treated with EPSST and 5-FU + EPSST group. These groups were continued up to the day of sacrifice (28 days post treatments). The isolated strain became recognized based totally on 16S rDNA sequence as Streptomyce sp. with accession number SAMN08349905. The chemical evaluations of EPSST were galacturonic, glucose, galactose, mannose, and arabinose with a relative ratio of 2.1: 1: 5.37: 1.62: 1.29 individually, with an average molecular weight (Mw) 9.687 × 103 g/mol. Also, the EPSST contained uronic acid (16%) and sulfate (12.149%) and no protein was detected. EPSST inhibited the DPPH radical activity. The findings of this study propose that EPSST inhibits 5-FU-induced mucositis through adjustment of oxidative stress, apoptosis, inflammatory factors, activation of antioxidant enzymes. The clinical administration of EPSST may recover the chemotherapy-induced intestinal dysfunction, consequently increasing the clinical efficiency of chemotherapy. In addition, the administration of EPSST reduced 5-FU-induced histopathological incongruities such as neutrophil infiltration, loss of cellular integrity, and villus and crypt distortion. The clinical administration of EPSST may recover the chemotherapy-induced intestinal dysfunction, consequently increasing the clinical efficiency of chemotherapy.

Evaluation of the therapeutic effects of rice husk nanosilica combined with platelet-derived growth factor in hepatic veno-occlusive disease.

Veno-occlusive disease is an important pattern of hepatotoxicity associated with antineoplastic drugs. The study investigated the possible therapeutic effects of RHS nanoparticles combined with a PDGF on veno-occlusive disease (VOD) in liver elicited in rats with DAC. In this work, nanosilica (SiO2) was successfully prepared from rice husk, and its physicochemical characteristics were investigated using EDX, XRD, N2 adsorption-desorption isotherm, SEM, and TEM. Forty-eight male Sprague-Dawely rats were distributed into 6 groups, with 8 rats in each. The first group served as the control. In the second group, animals were infused with DAC (0.015 mg/kg; 1-3 days) by intraperitoneal injection (i.p.). In the third group, rats were injected i.p. with DAC, and then at 24 h following the last dose of DAC, received nano-RHS incorporated with PDGF twice a week for 4 weeks. In the fourth group, normal animals were injected with RHS. In the fifth group, normal rats received PDGF, and in the sixth group, normal rats received nano-RHS combined with PDGF. The prepared nanosilica showed type II adsorption isotherm characteristic for mesoporous materials with a specific surface area of 236 m2/g. TEM imaging confirmed the production of nanoparticles via the followed preparation procedure. Radical scavenging potential for nano-RHS was determined using two different in-vitro assays: DPPH, and ABTS radicals. The results of this work show that administration of nano-RHS combined with PDGF significantly reversed the oxidative stress effects of DAC as evidenced by a decrease in liver function. It can be concluded that the nano-RHS combined with PDGF is useful in preventing oxidative stress and hepatic VOD induced by chemotherapy such as DAC.

Effect of polysaccharide from Bacillus subtilis sp. on cardiovascular diseases and atherogenic indices in diabetic rats.

BACKGROUND: Diabetes mellitus induces chronic complications such as cardiovascular damage, cataracts and retinopathy, nephropathy, and polyneuropathy. The main aim of the study was to isolate and identify both of bacterial strain and exopolysaccharide to assess the possible efficiency of exopolysaccharide (BSEPS) from Bacillus subtilus sp .suppress on cardiovascular diseases, atherogenic and coronary risk indices in diabetic rats. METHODS: The bacterial strain used was isolated from mangrove tree sediment by serial dilution and the spread-plate technique and identified by morphological, physiological, and biochemical characteristics, and by 16S rRNA analysis. The BSEPS was extracted from the bacterial supernatant by four volumes child ethanol then the functional groups, MW and chemical analysis were detected by Fourier-transform infrared (FTIR), gel permeation chromatograph (GPC) and High-performance liquid chromatography (HPLC). Also an antioxidant activity was measured by using 2,2-diphenyl-1-picrylhydrazyl (DPPH). Thirty-two male Sprague-Dawley rats were equally randomized into four groups: control group supplemented with normal saline (Group I); the second group supplemented with BSEPS (Group II); diabetic group supplemented with normal saline (Group III) and the diabetic group supplemented with BSEPS (Group IV). Diabetes was induced by Streptozotocin (STZ) (65 mg/kg BW) intraperitoneally. BSEPS (100 mg/kg BW) was administered orally for four weeks, following STZ induction. RESULTS: The isolated strain was identified based on 16S rRNA sequence as Bacillus subtilis sp. suppress. A preliminary chemical analysis of BSEPS indicated that the monosaccharides were mannuronic acid, glucuronic acid, glucose, galactose, and mannose in a molar ratio of 1.6:1.5:1.0:2.3:1.4, respectively, with a molecular weight of 1.66 × 10(4) g mol(-1) and a molecular number of 7.64 × 10(3) g mol(-1). BSEPS inhibited 2,2-diphenyl-1-picrylhydrazyl radical activity, and BSEPS supplement reduced glucose (p < 0.05) and troponin levels while insulin levels increased (p < 0.05). BSEPS also reduced total serum cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides, and elevated high-density lipoprotein-cholesterol (HDL). In parallel, intercellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) levels in STZ-induced diabetic rats were reduced. Moreover, polysaccharides reduced atherogenic and coronary risk indices, which were confirmed by histopathological examination of the heart and aorta. CONCLUSIONS: Our study suggests that BSEPS improves hyperglycemia, dyslipidemia, and cardiovascular disease risk in STZ-induced diabetic rats.

Protective Effect of Adansonia digitata against Isoproterenol-Induced Myocardial Injury in Rats.

The baobab fruit (Adansonia digitata) was analyzed for proximate composition, amino acids, and minerals. The fruit pulp was found to be a good source of carbohydrates, proteins, phenols, and substantial quantities of K, Ca, and Mg. Amino acid analyses revealed high glutamic and aspartic acid, but the sulfur amino acids were the most limited. The present study was designed to investigate the role of Adansonia digitata (Baobab fruit pulp) against isoproterenol induced myocardial oxidative stress in experimental rats by demonstrating the changes in tissue cardiac markers, some antioxidant enzymes, interleukin-1 ß (IL-1 ß), monocyte chemoattractant protein-1(MCP-1), myeloperoxidase (MPO), Collagen-1, galectin-3, and serum corticosterone. The activities of enzymatic antioxidant glutathione peroxidase (GPX) and non-enzymatic antioxidant reduced glutathione (GSH) in the heart tissue; additionally, histopathological examination of the heart was estimated. Male albino rats were randomly divided into four groups of ten animals each. Group I served as normal control animal. Group II animals received isoproterenol (ISP) (85 mg/kg body weight intraperitonealy (i.p.) to develop myocardial injury. Group III were myocardial oxidative animals treated with Baobab fruit pulp (200 µg/rats/day) for 4 weeks. Group IV received Baobab fruit pulp only. The data suggested an isoproterenol increase in levels of cardiac marker enzymes [creatine kinase MB (CK- MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)], IL-1ß, MCP-1, MPO, Collagen, and galectin-3, with concomitant decrease in the activities GPX and GSH in heart tissue as well as corticosterone in serum. Baobab fruit pulp brings all the parameters to near normal level in ISP-induced myocardial infarction in rats. Histopathological examination of heart tissue of ISP-administered model rat showed infiltration of inflammatory cells and congestion in the blood vessels. However, treatment with Baobab fruit pulp (200 µg/rats/day) showed predominantly normal myocardial structure and no inflammatory cell infiltration. It has been concluded that Baobab fruit pulp has cardio protective effect against ISP-induced oxidative stress in rats.

Efficiency of calcium phosphate composite nanoparticles in targeting Ehrlich carcinoma cells transplanted in mice.

The present study aimed to investigate the mode of action of nano-CaPs in vivo as a therapy for solid tumor in mice. To achieve this goal, Ehrlich Ascites Carcinoma (EAC) was transplanted into 85 Swiss male albino mice. After nine days, the mice were divided into 9 groups. Groups 1 and 2 were allocated as the EAC control. Groups 3 and 4 were injected once intratumorally (IT) by nano-calcium phosphate (nano-CaP). Groups 5 and 6 received once intraperitoneal injection (IP) of nano-CaP. Groups 7, 8, and 9 received nano-CaP (IP) weekly. Blood samples and thigh skeletal muscle were collected after three weeks from groups 1, 3, 5, and 7 and after four weeks from groups 2, 4, 6, and 8. On the other hand, group 9 received nano-CaP (IP) for four weeks and lasted for three months to follow up the recurrence of tumor and to ensure the safety of muscle by histopathological analysis. Tumor growth was monitored twice a week throughout the experiment. DNA fragmentation of tumor cells was evaluated. In thigh tissue, noradrenaline, dopamine, serotonin (5HT), and gamma-aminobutyric acid (GABA) were measured. In serum, 8-Hydroxy-deoxyguanosine (8-OHDG), adenosine triphosphate (ATP), and vascular endothelial growth factor (VEGF) were analyzed. Histopathological and biochemical results showed a significant therapeutic effect of nano-CaP on implanted solid tumor and this effect was more pronounced in the animals treated IP for four weeks. This improvement was evident from the repair of fragmented DNA, the significant decrease of caspase-3, 8-OHDG, myosin, and VEGF, and the significant increase of neurotransmitters (NA, DA, 5HT, and GABA). Additionally, histopathological examination showed complete recovery of cancer cells in the thigh muscle after three months.

Efficacy of polysaccharide from Alcaligenes xylosoxidans MSA3 administration as protection against γ-radiation in female rats.

Damage to normal tissues is a consequence of both therapeutic and accidental exposures to ionizing radiation. A water-soluble heteropolysaccharide called AXEPS, composed of glucose, galactose, rhamnose and glucouronic acid in a molar ratio of nearly 1.0:1.6:0.4:2.3, respectively, was isolated from culture medium of strain Alcaligenes xylosoxidans MSA3 by ethanol precipitation followed by freeze-drying. Chemical analysis, Fourier-transform infrared (FTIR) and chromatographic studies revealed that the molecular weight was 1.6 × 10(4) g mol(-1). This study was designed to investigate the radioprotective and biological effects of AXEPS in alleviating the toxicity of ionizing radiation in female albino rats. A total of 32 female albino rats were divided into four groups. In the control group, rats were administered vehicle by tube for four weeks. The second group was administered AXEPS (100 mg/kg) orally by gavage for four weeks. Animals in the third group were exposed to whole-body γ-rays (5 Gy) and remained for 2 weeks without treatment. The fourth group received AXEPS (100 mg/kg) orally by gavage for two weeks before being exposed to whole-body γ-rays (5 Gy), then 24 h post γ-rays, they received AXEPS (100 mg/kg) in a treatment continuing till the end of the experiment (15 days after the whole-body γ-irradiation). Oral administration of AXEPS (100 mg/kg) significantly reversed the oxidative stress effects of radiation, as evidenced by the decrease in DNA damage in the bone marrow. Assessment of apoptosis and cell proliferation markers revealed that caspase-3 significantly increased in the irradiated group. Moreover, a significant decrease in the hematological constituents of peripheral blood, the chemotactic index and CD8+ T cells were observed in animals in the irradiation-only group, whereas an increase in the lymphocyte index was observed in animals in that group. In contrast, AXEPS treatment prevented these alterations. From our results, we conclude that AXEPS is a potent antioxidant and treatment agent for protection from γ-rays.

The anti-ulcerative colitis effects of Annona squamosa Linn. leaf aqueous extract in experimental animal model.

This study aimed to evaluate the anti-inflammatory effects of Annona squamosa (A. squamosa) leaf aqueous extract against acetic acid induced colitis in rats with a trial to explore its use for the treatment of colon inflammation. Sprague Dawley rats weighing 180-200 g were used in this study. Treatment with A. squamosa extract at dose 300 mg/kg for 4 weeks counteracted acetic acid induced ulcerative colitis by a significant decrease (P<0.05) of colonic tissue of malondialdehyde (MDA) and significant increases of catalase (CAT), glutathione (GSH) and glutathione peroxidase (Gpx) compared to ulcerative colitis control group. Furthermore, induction of oxidative stress was observed in the colonic tissue through the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) which significant increase in colonic tissue DNA by acetic acid. Moreover AA induced significant increase in serum interleukin-10 (IL10), tumor necrosis factor-α (TNF-α), transforming growth factor (TGF 1ß), and C reactive protein (CRP) as compared to the control group. On the contrary, our results showed AA induced significant decrease of vascular endothelial growth factor (VEGF) and thyroid hormones triiodothyronin and thyroxin (T3 & T4) in installed group with AA as compared to control which significantly improved after treatment with A. squamosa leaf extract. Histopathological observation in our study confirmed the biochemical study. Thus, therapeutic method offer a sign to analyze further the effectiveness of A. squamosa as a unique agent for alleviating colitis.

Evaluation of mesenchymal stem cells in treatment of infertility in male rats.

INTRODUCTION: The present study aimed to elucidate the therapeutic effects of mesenchymal stem cells (MSCs) derived from the bone marrow of rats (BM) against toxic effects of lead (Pb) on the male gonads of experimental rats. METHODS: The experimental animals were exposed to lead in the form of lead nitrate (LN) one quarter of the LD50. The efficacy of MSCs to reduce gonado-totoxicity induced by lead nitrate at 21, 30 and 60 days, was evaluated experimentally in male rats. RESULTS: The results showed that testosterone levels and semen quality ameliorated following treatment with MSCs. Also, superoxide dismutase, glutathione peroxidase and catalase levels were increased 21, 30 and 60 days post treatment of MSCs. Moreover, a decrease in genomic DNA alteration and percentage of fragmented DNA was recorded after MSCs treatment. Lead nitrate caused degeneration, necrosis, interstitial edema, and reduction in spermatogenic activity in some seminiferous tubules. The LN-induced changes in histopathologic findings of testis were partially reversed by treatment with MSCs. Histological examination of testis showed deformities in morphology of testis in test animals with gross damage within the seminiferous tubules in Lead nitrate group. The LN-induced changes in histopathologic findings of testis were partially reversed by treatment of MSCs. CONCLUSIONS: It was concluded that lead is a gonadotoxic with a tendency of suppressing semen characteristics and testosterone levels of animals, the presence of MSCs was found to alleviate the toxic effects of lead. We conclude that MSCs derived from the bone marrow of rats can be an effective therapy of LN induced gonado toxicity, thus can contribute to the treatment of infertility.