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Osteoporosis is a disease characterized by low bone mass, deterioration of bone tissue, and disruption of bone microarchitecture: it can lead to compromised bone strength and increased risk of fractures. Secondary osteoporosis is mostly glucocorticoid-induced osteoporosis (GIOP). According to traditional Chinese medicine, the kidney influences bone, and bone loss are associated with kidney and liver inadequacies. We testedAllolobophora caliginosaextract (EE) andAllolobophora caliginosacoelomic fluid (CF) for anti-osteoporotic activity against GIOP. 28 male mice were separated randomly into two groups; the control received distilled water, and the second group received 1 mg/kg dexamethasone daily for 28 days. The second group was divided randomly into three groups. The first OP subgroup received distilled water orally every other day for 28 days. The other two OP subgroups received EE (45 mg/kg body weight) and CF(20 mg/kg) orally for 28 days. EE and CF preserved cortical and trabecular bone loss, decreased bone marrow space, and enhanced chondrocyte production. EE and CF maintained hepatic necrosis in the liver and decreased renal degeneration in the kidney caused by GIOP. In this study, Histological images showed that EE at 45 mg/kg was highly effective as an anti-osteoporotic against GIOP, while CF at 20 mg/kg was moderately effective.

Background: Diabetes mellitus is the most common health problem in the world. Silver nanoparticles (AgNPs) exposed great intrinsic anti-inflammatory, antibacterial, antiviral, and antifungal activities. Chitosan is an oligosaccharide biopolymer with a great ability to lower hyperglycemia, and ascorbic acid is a water-soluble vitamin with strong antioxidant activity. Objective: The present study aimed to estimate AgNPs/chitosan/ascorbic acid nanocomposite (Ag-NCs) anti-diabetic properties in streptozotocin-induced diabetic rats. Method: Eighteen male Wistar albino rats were divided into three main groups (6 rats/group); control, diabetic, and Ag-NCs groups. Control group: after a single dose of citrate buffer at PH 4.5 (0.1 mol/L, i.p), the rats orally received 1 ml distilled water daily for four weeks. The diabetic model was induced by a single dose of streptozotocin (60 mg/kg, i.p) for type 1 diabetes and the rats orally received 1 ml distilled water daily for four weeks. The diabetic group was treated orally with Ag-NCs (0.25 mg/Kg body weight) daily for four weeks. Results: AgNPs/chitosan/ascorbic acid nanocomposite group showed a reduction in the concentrations of glucose, NO, MDA, LDL, and the activities of AST, ALT, ALP, and GGT. At the same time, it caused a general increase in insulin, albumin, TB, TC, TG, HDL, CAT, SOD, and GSH levels. The histopathological investigation illustrated regeneration of damaged pancreatic beta cells and a clear improvement in the hepatic architecture. Conclusion: The suggested mechanism of action for Ag-NCs in decreasing diabetic complications in the liver involved two pathways; the hypoglycemic activity and the antioxidant role of AgNPs, chitosan, and ascorbic acid.

Background: Nanoparticles have many properties, depending on their size, shape, and morphology, allowing them to interact with microorganisms, plants, and animals. Objectives: Investigatation of the therapeutic effects biocompatible zinc oxide nanoparticles (ZnO NPs) on P. equorum infection in rats. Methods: Thirty-six rats were divided into two divisions are: the first division is noninfected groups were allocated into three groups. Group 1: Control, Group 2: ZnO NPs (30mg/kg) and group 3: ZnO NPs (60mg/kg). The second division is infected groups were allocated into three groups. Group 1: vehicle, group 2: ZnO NPs (30mg/kg) and group 3: ZnO NPs (60mg/kg). Findings: Biocompatible ZnO NPs caused a significant decrease in liver functions, LDL, cholesterol, triglycerides, MDA and NO. While it caused a significant increase in HB, HDL, BCHE, GSH, CAT, and GST in infected treated rats. The histological inflammation and fibroplasia scores showed a significant enhancement during the treatment with ZnO NPs (30, 60mg/kg) compared to the infected untreated animals that scored the highest pathological destruction score. Immunohistochemical markers of NF-κB showed a significant decrease during the treatment with ZnO NPs (30, 60mg/kg) compared to the infected untreated animals. Main conclusions: Biocompatible Zinc Oxide Nanoparticle is a promising treatment modality against parasitic infection through its powerful anthelmintic, antioxidant, healing promotion, and anti-inflammation effects.

Background: Non-alcoholic fatty liver disease (NAFLD) is a considerable public health concern due to the excessive dietary consumption of high caloric diet and subsequent obesity. Additionally, splenectomy is considered one of the major common risk factors for NAFLD. Objective: Regardless of the non-alcoholic fatty liver disease (NAFLD) being the most common chronic disorder, there is no effective cure for it. Therefore, the current study aimed to investigate the efficacy of Holothuria arenicola extract (HaE) on hepatic steatosis in splenectomized (SPX) rats fed High fat diet (HFD). Methods: Male Wistar rats (n=28) were randomly assigned to four groups: sham rats fed a standard diet, sham rats+ HFD, SPX+HFD and SPX+HFD+HaE. The estimation of hematological and some biochemical parameters, as well as oxidative status, were analyzed. Results: Oral administration of HaE caused a significant amelioration in all hematological parameters relative to untreated splenectomized rats. Concerning lipid metabolism, HaE treatment caused a pronounced amelioration in lipid metabolism, as indicated by the decreased total cholesterol, triglycerides and LDL-cholesterol contents, as well as the increased HDL- cholesterol level. HaE treatment significantly enhanced hepatic function, as exhibited by the reduction in liver enzyme activities as well as the increase in protein and albumin content. Moreover, HaE could retard the hepatic oxidative stress via a pronounced increase in hepatic GSH content and antioxidant enzyme activities besides decreasing MDA, NO and H2O2 formation. Conclusion: HaE could be utilized as a potential alternative hepatoprotective remedy via lipid metabolism and oxidative damage attenuation.

Background: P.clarkii hemolymph has several pharmacological activities against inflammation, bacteria and tumor. The current study aimed to explore the efficacy of P.clarkii hemolymph against the renal toxicity induced by Gentamicin (GM) in rats. Methods: The animals were divided randomly into three groups (six per group): control, GM and P.clarkii. Tissues toxicity was established after injection of GM daily for eight days at a dose 100 mg/kg. Kidney functions, liver functions, oxidative stress markers and histopathology of tissues were investigated in the study. Results: P.clarkii treated rats showed a significant decrease in urea, creatinine, uric acid, ALT, AST, and MDA levels while GSH and CAT levels increased. The histology of kidney investigation showed partial restoration of renal architecture. Conclusion: The study results revealed the protective role of p.clarkii hemolymph against gentamicin-induced acute kidney injury in rats.

Triple-negative breast cancer is one of the most aggressive breast cancer. The first therapeutic option is chemotherapy, often based on anthracycline as doxorubicin. However, chemotherapy efficacy is limited in by the presence of P-glycoprotein (Pgp), a membrane transporter protein that effluxes doxorubicin, reducing its cellular accumulation and toxicity. Inhibiting Pgp activity with effective and non-toxic products is still an open challenge. In this work, we demonstrated that the natural product Glabratephrin (Glab), a prenylated flavonoid from Tephrosia purpurea with a unique chemical structure, increased doxorubicin accumulation and cytotoxicity in triple negative breast cancer cells with high levels of Pgp, characterized by both acquired or intrinsic resistance to doxorubicin. Glab also reduced the growth of Pgp-expressing tumors, without adding significant extra-toxicities to doxorubicin treatment. Interestingly, Glab did not change the expression of Pgp, but it reduced the affinity for Pgp and the efflux of doxorubicin, as suggested by the increased Km and the reduced Vmax. In silico molecular docking predicted that Glab binds two residues (phenylalanine 322, glutamine 721) localized in the transmembrane domains of Pgp, facing the extracellular environment. Moreover, site-directed mutagenesis identified glycine 185 as a critical residue mediating the reduced catalytic efficacy of Pgp elicited by Glab. We propose Glab as an effective and safe compound able to reverse doxorubicin resistance mediated by Pgp in triple negative breast cancers, opening the way to a new combinatorial approach that may improve chemotherapy efficacy in the most refractory and aggressive breast cancer.

Toxocara vitulorum is a common gastrointestinal nematode of buffaloes and cattle, primarily young calves. This parasitic infection is distributed worldwide, causing a huge economic loss due to reduced meat and milk production and animal mortality. Several studies have indicated that silver nanoparticles have an effective anthelmintic activity. Thus, this study aimed to evaluate the anthelmintic effects of different concentrations of silver nanoparticles on adult Toxocara vitulorum in vitro. Male and female adult worms were incubated for 48 h in 50, 100, and 200 mg/L silver nanoparticles synthesized using lemon juice. Oxidative stress markers, in addition to light and scanning electron microscopic studies of treated worms, were assessed following 48 h incubation in 200 mg/L silver nanoparticles. Light and scanning electron micrographs of treated worms revealed damage in the muscular layer, destruction of the cuticle, distortion in lips structure, and deformed excretory pore and sensory papillae. Also, oxidative stress markers recorded an increase in malondialdehyde and nitric oxide and decreased levels of glutathione reduced, glutathione S-transferase, and catalase after exposure to silver nanoparticles. In Conclusion, the current study demonstrated a substantial destructive effect of silver nanoparticles on adult Toxocara vitulorum, indicating its potential as an anthelmintic alternative to the more expensive drugs.

Aims:The present study aimed to evaluate anti-diabetic properties of AgNPs/chitosan/ascorbic acid nanocomposites (Ag-NCs) in streptozotocin-induced diabetic rats. Main methods: Eighteen male Wistar albino rats were divided into three main groups (6 rats/group); control, diabetic and Ag-NCs groups. Control group: after a single dose of citrate buffer (0.1 mol/l, i.p), the rats orally received 1 ml distilled water daily for four weeks. The diabetic model was induced by a single dose of streptozotocin (60 mg/kg, i.p) for type 1diabetes. Diabetic groups were treated orally with and Ag-NCs (0.25mg/Kg body weight) daily for four weeks. Key findings:AgNPs/chitosan/ascorbic acid nanocomposite group showed a reduction in the concentrations of glucose, NO, MDA, creatinine, urea and uric acid. At the same time, it appeared a general increase in insulin, CAT, and SOD activities and GSH concentration. The histopathological investigation illustrated a clear improvement in renal architecture. Significance: The suggested mechanism of action for Ag-NCs in decreasing diabetic nephropathy includes two pathways; the hypoglycemic activity and the antioxidant role of Ag-NCs&nbsp

Background: Colorectal cancer is one of the most serious gastrointestinal cancers in Africa and its prevention is a pronounced challenge in contemporary medicine worldwide. Objective: The present study aimed to develop nanoemulsion drug delivery system using pomegranate polysaccharides (PGPs) as an alternative cancer remedy, and then the evaluated its biological activities. Methods: The PGPs yield and chemical composition were evaluated, and then a PGPs nanoemulsion (PGPs-NE) was prepared using the self-emulsification technique with an oil phase. The physicochemical characterization of PGPs-NE was then analyzed. The in vitro antioxidant, anti-inflammatory activities, and antitumor potency of PGPs and PGPs-NE were also evaluated. Results: The PGPs yield was 10%. The total sugar and protein content of PGPs was 44.66 mg/dl and 19.83μg/ml, respectively. PGPs were mainly composed of five monosaccharides including fructose, glucose, galactose, rhamnose, and arabinose. Concerning physiochemical characterization, the formulated PGPs-NE had three optical absorption bands at 202, 204, and 207nm and a transmittance of 80%. Its average hydrodynamic particle size was 9.5nm, with a PDI of less than 0.2 and a negative zeta potential (-30.6 mV). The spherical shape of PGPs-NE was confirmed by a transmission electron microscope study, with an average size of less than 50 nm. Additionally, the method used to prepare the PGPs-NE formulation provided high entrapment efficiency (92.82%). The current study disclosed that PGPs-NE exhibited strong antioxidant, anti-inflammatory, and antitumor agent potency compared to that of free PGPs. Conclusion: These promising current findings provide evidence for the possible efficacy of novel PGPs-NE as an alternative treatment for CRC.

In the present study, the effect of different biocompatible concentrations from ZnO nanoparticles (ZnO NPs) on the physiological state and surface topography of the nematode P. equorum was determined in vitro. Different concentrations of ZnO NPs (100, 200, 300 and 400 mg/l) synthesized using the egg white were prepared followed by the incubation of parasitic worms with these concentrations in vitro. The physiological state of treated worms such as oxidative stress markers, enzymatic activities and biochemical parameters in addition to the surface topography was determined and compared with control untreated worms. In comparison to control worms, it was observed that at high concentrations of ZnO NPs, most of the treated worms showed an increase in the levels of ALT, AST and ALP (worm muscle damage, and gonad injury); enhancement of the total protein content (worm cellular dysfunction); significant increase in MDA level (free radical-mediated worm cell membrane damage); depletion in GST and GSH activities (reduced ability to clear toxic compounds like lipid peroxides); CAT depletion (superoxide dismutase and hydrogen peroxide toxicity) and NO increase (detoxification activity and stressful conditions on worms). SEM showed that there was a modified morphological appearance in the surface of treated worms; lips were wrinkled with irregularly arranged denticles, weathering of cuticle, bursts of cuticle layers, disruption of surface annulations and erosion of surface papillae of male around the cloacal opening. ZnO NPs at environmentally relevant concentrations achieved a significant antihelminthic activity against P. equorum which represents a successful model used in parasite control experiments.

The present investigation attempted study the potential use of the Holothuria arenicola saponin (HaS) against Ehrlich Ascites Carcinoma (EAC) tumor model in female Swiss albino mice. The HPLC studies of the extracted saponin showed the peak at retention time 5.19 min. was is matched with the standard saponin with total amount 34.87%. Significant improvements were detected in the tumor markers, complete blood count, antioxidant system, liver function and kidney function of HaS-treated mice. The present study demonstrated that HaS is a potent natural product that has promising antineoplastic efficacy.

Cairo University was the first academic institution in Egypt to establish an Institutional Animal Care and Use Committee (IACUC), as mandated by the World Organisation for Animal Health (OIE). Animal-based research should be performed in accordance with international regulations to monitor the humane care and use of the laboratory animals. Until 2018, the formal training of researchers in the appropriate and correct methods of animal handling during sampling and administration, as well as their husbandry demands, was an uncommon practice in Egypt. In 2018, the Egyptian Association for Animal Research Advancement (EAARA) organised the first international course in laboratory animal science (LAS), in collaboration with Utrecht University (The Netherlands) and the Faculty of Science, Cairo University, to raise researchers’ awareness and increase their knowledge of the principles that govern the humane use and care of laboratory animals. A total of 26 researchers from a number of fields (veterinary medicine, dentistry, science, medicine, pharmacy and agriculture) enrolled in the course. In the responses to the post-course questionnaire, 24 (92.3%) participants stated that the principles of animal welfare (Three Rs) were well explained. In addition, 18 (69%) participants found that the course improved their skills in animal sampling and handling. Of the 26 participants, 22 (84.6%) became aware of their responsibility towards their experimental animals and agreed that the different methods of euthanasia were well explained. In conclusion, the general assessment of the course revealed a positive outcome regarding the culture of animal care; the course was repeated a year later, and several participants were enlisted as trainers in this second course.

The current study aimed to evaluate the antibacterial, anti-inflammatory, analgesic, and renoprotective effects of echinochrome pigment extracted from sea urchin. The disk diffusion method was used for the antibacterial activity of echinochrome against four different bacterial strains; Salmonella typhimurium, Pseudomonas aeroginosa, Staphylococcus aureus, and Listeria monocytogenes. While, acetic acid-induced writhing, formalin-induced licking, and hot plate latency assays evaluate the analgesic activity. The biochemical and oxidative stress markers of kidneys, as well as the histopathological examination, were measured to evaluate the renoprotective activity of echinochrome for cecal ligation and puncture-induced renal injury in rats. Echinochrome pigment exhibited in vitro antibacterial activity against all aforementioned bacterial species besides a powerful anti-inflammatory impact in vitro by the effective stabilization of the RBCs membrane and in vivo by decrease levels of serum IL6 and TNF-α. What's more, echinochrome showed a notable analgesic efficacy as well as an enhancement of the kidney's biochemical markers, oxidative stress status, and histopathological screening. Ech attenuated cecal ligation and puncture-induced renal injury by improving renal biomarkers, suppressing reactive oxygen species propagation as well as its antibacterial, anti-inflammatory, and anti-nociceptive activities. PRACTICAL APPLICATIONS: Sea urchins are rich in pharmacologically important quinone pigments, specifically echinochrome. The current study aimed to evaluate the role of echinochrome as a renal protective remedy in sepsis and clarify its biological activities. Echinochrome exhibited antibacterial activity in vitro against Salmonella typhimurium, Pseudomonas aeroginosa, Staphylococcus aureus, and Listeria monocytogenes. Our results revealed that echinochrome protects the kidney against damage caused by sepsis in rats. Echinochrome can use in the treatment of sepsis as an antibacterial, anti-inflammatory, and antioxidant agent.

The present study evaluates the prophylactic role of Ananas comosus ethanolic extract (ACEE) against sodium oxalate (NaOx) - induced nephrolithiasis. Forty two rats were allocated into the following set of groups (6 rats/set group). Normal rats divided to two groups, one of them received distilled water (Control group) and the other received ACEE (1000 mg/kg body weight, p.o) for 7 consecutive days. Urolithiatic rat groups which divided into five subgroups injected with sodium oxalate (70 mg NaOx /kg body weight, i.p) for 7 days; and concurrently received oral administration of distilled water (Urolithiatic group, Vehicle), ACEE and Cystone. Interestingly, ACEE showed a beneficial effect in preventing stone formation. Significant reductions were obtained in the urinary and serum calcium and phosphate excretion along with an increase in magnesium excretion in urolithiatic rats treated with ACEE. Urolithiatic rats treated with ACEE and cystone significantly increased the urinary volume. Administration of ACEE caused significant amelioration in renal function which suggests antilithiatic activity of ACEE. Moreover, urolithiatic rats treated with ACEE significantly attenuated oxidative damage induced by NaOx. In conclusion, ACEE has antilithiatic efficacy may be due to its diuretic activity, antioxidant activity, beside its bioactive constituents which affecting calcium oxalate crystallization.

Supplemental Material, sj-pdf-1-atl-10.1177_02611929211016851 for Culture of Care Enhancement in Egypt: The Impact of Laboratory Animal Science Training on Participants’ Attitudes by Mohamed Hosney, Abeer M. Badr, Sohair R. Fahmy, Ahmed Afifi, Vera Baumans and Khadiga M. Gaafar in Alternatives to Laboratory Animals

Supplemental Material, sj-pdf-2-atl-10.1177_02611929211016851 for Culture of Care Enhancement in Egypt: The Impact of Laboratory Animal Science Training on Participants’ Attitudes by Mohamed Hosney, Abeer M. Badr, Sohair R. Fahmy, Ahmed Afifi, Vera Baumans and Khadiga M. Gaafar in Alternatives to Laboratory Animals

Background Cholestasis is the major cause of bile acid accumulation leading to liver damage. Chronic infection of worms can modulate the immune response towards T helper (Th)2-related cytokines. The present study aims to evaluate the protective impact of an ascarid nematode Toxocara vitulorum extract (TvE) against alpha-naphthylisothiocyanate (ANIT)-induced cholangitis male wistar rat model compared to ursodeoxycholic acid (UDCA) as a standard drug. Results Pretreatment with TvE and/or UDCA induced a marked reduction in the levels of liver function tests and malondialdehyde, while antioxidant markers were increased compared to cholestatic rats. Pretreatment with either TvE or combination before cholangitis induction attenuated the predominant Th1-related cytokines (IFN-γ and TNF-α) to Th2 (IL-13 and IL-10). TvE administration promoted higher expression levels of Bcl-2 protein and lower levels of caspase-3 compared to cholestatic rats. Conclusions Treatment with TvE has improved the liver functions and elevated the levels of oxidative stress markers. The upregulation of Th2-related cytokines and suppression of apoptosis through caspase-3 might be considered as a potential mechanism of TvE. Thereby, this natural extract revealed an opportunity for use in treatment of cholangitis disease.

Background: Cucumber extract is often used for skin problems, wrinkles, sunburn, and as an antioxidant. Thereby, the main objective of the present investigation was to develop a topical skincare cream (w/o) loaded with the sea cucumber,Holothuria arenicolaextract (HaE). Methods: Oil in water emulsion-based cream was prepared by incorporating liquid paraffin, soft wax, cetostearyl alcohol in the oil phase, and borax in the water phase respectively with 1 gm of HaE. The evaluation of HaE cream was done on different parameters like ph, viscosity, spreadability, extrudability, irritancy and stability. Results: HaE showed good appearance, homogeneity, spreadability, diffusion, consistency, pH, extrudability, and spreadability without any irritancy to skin. The present results showed that HaE cream has radical scavenging activity in range from 57 to 70 % and NO scavenging activity in range from 25 to 49 %. Conclusion: The formulated HaE cream was successfully developed that met the relevant pharmaceutical characteristics form. The developed HaE cream could be added in topical formulations in order to protect skin against damage caused by free radicals due to its antioxidant activity.&nbsp

Despite the progress in using silver nano products in many fields, including medicine, food, and industry, their effects on the environment need more attention. Therefore, the current study aimed to assess the effect of silver/saponin nanocomposites (Ag/S NCs) for the first time on the aquatic environment by using freshwater clam, Caelatura aegyptiaca, as a fundamental bioindicator in the freshwater system. Following the preparation and characterization of Ag/S NCs by using atomic absorption spectrophotometer, UV–Vis spectrophotometer, X-ray diffraction, transmission electron microscopy, and acute toxicity study, we exposed the clam to three different doses of Ag/S NCs (12.5, 25 and 50 mg L−1) for consecutive 6 days. All Ag/S NCs concentrations caused a significant increase in malondialdehyde and nitric oxide while induced a notable decrease in glutathione and catalase levels in all studied organs. Moreover, the histological alternations were observed in gills, labial palp, and foot tissues, particularly at dose 50 mg L−1. From the results of our work, we concluded that toxicity of Ag/S NCs on freshwater clam leads to an oxidative stress response as well as histopathological changes. Besides, we assumed that Coelatura aegyptiaca could be used as a sensitive bioindicator for monitoring water pollution caused by different nanoparticles. Therefore, we do recommend performing further studies by using fresh clam to provide a better assessment for our aquatic environment to prevent water pollution locally and globally.

Background Bivalves can accumulate and concentrate most pollutants, even if they are present in somewhat low concentrations. The present study aimed to use freshwater bivalveas for the first time as vital indicator for silver/chitosan nanocomposites (Ag-CS NCs) in the freshwater environment. Methods Following the preparation and characterization of Ag-CS NCs by using UV–vis spectrophotometer, X-ray diffraction, transmission electron microscopy, and acute toxicity study, the animals exposed to three different dose of nano chitosan (CS), AgNPs, and Ag-CS NCs (12.5, 25 and 50 mg/L) for consecutive 6 days. Results Ag-CS particles were in size range of 8–19 nm. The nominal concentrations for Ag-CS NCs were 12.5, 25 and 50 mg Ag L−1 were corresponding to measured concentration of AgNPs 0.37, 0.81, and 1.65 mg Ag L−1, respectively. All concentrations of Ag-CS NCs caused a significant increase in MDA and NO, while GSH and CAT levels decreased significantly in all organs. Histological investigation of the gills, labial palp and foot tissues showed alternation after exposure to Ag-CS NCs, especially at dose 50 mg/L. Conclusion The present study showed that exposure to Ag-CS NCs caused oxidative stress responses in Coelatura aegyptiaca and histological changes in the organs. These physiological and histological changes observed after exposure to Ag-CS NCs were most likely the result of the action of AgNPs themselves while the effect of chitosan on these changes was negligible. We concluded that Coelatura aegyptiaca was a sensitive bio-indicator for monitoring of the past and the present water pollution by nanoparticles.

The present study was designed to evaluate the protective effects of echinochrome (Ech) on intrahepatic cholestasis in rats induced by a single (i.p.) injection of alpha-naphthylisothiocyanate (ANIT) (75 mg/kg body weight). The rats were pre-treated orally for 48hr (one dose / 24hr) with Ech (1, 5 and 10 mg/kg body weight) or ursodeoxycholic acid (UDCA) 80 mg/kg body weight drug then, injected with ANIT. ANIT markedly increased serum activities of alanine amino transaminase (ALT), aspartate amino transaminase (AST) and alkaline phosphatase (ALP), which was accompanied by a massive inflammation of epithelial cells on bile duct at 24h after ANIT injection. ANIT also increased the levels of total protein (TP), total bilirubin (TB), direct bilirubin (DB), indirect bilirubin (IB), however decrease albumin content (ALB). In addition ANIT increased hepatic MDA and NO level and decreased GSH level and GST activity. The Ech exerted hepatoprotective and anticholestatic effects as assessed by a significant decrease in the activities of serum AST, ALT and ALP, and the levels of TP, TB, DB and IB as well as liver MDA level and NO level. In conclusion, Ech was found to possess hepatoprotective effect against intrahepatic cholestasis induced by hepatotoxin such as ANIT. Resumo O presente estudo destinou-se a avaliar os efeitos protetores do Ech na colestase intra-hepática em ratos induzidos por uma única injeção (i.p.) de alfa-naftilisotiocianato (ANIT) (75 mg / kg de peso corporal). Os ratos foram pré-tratados oralmente durante 48 horas (uma dose / 24 horas) com cada (1, 5 e 10 mg / kg de peso corporal) e ácido ursodeoxicólico (UDCA) 80 mg / kg de peso corporal, em seguida, injetado com ANIT. ANIT atividades de soro marcadamente aumentadas de alanina amino transaminasa (ALT), aspartato de amino transaminases (AST) e fosfatase alcalina (ALP), que foi acompanhada por uma inflamação maciça de células epiteliais no ducto biliar às 24h após a injeção de ANIT. A ANIT também aumentou os níveis de proteína total (TP), bilirrubina total (TB), bilirrubina direta (DB), bilirrubina indireta (IB), no entanto, diminuem o teor de albumina (ALB). Além disso, a ANIT aumentou o nível de MDA hepático e NO e diminuiu o nível de GSH e a atividade de GST. O Ech exerceu efeitos hepatoprotectores e anticolestáticos como avaliado por uma diminuição significativa nas atividades de AST sérica, ALT e ALP e os níveis de TP, TB, DB e IB, bem como o nível de MDA no fígado e o nível de NO. Ech foi encontrado para possuir efeito protetor no fígado contra a colestase intra-hepática induzida por hepatotoxina, como a ANIT.

Rodents are widely used for animal research in Egypt. Pentobarbital is the most common anesthetic agent; however overdoses may affect the experimental outcomes and limit the use of tissues. To investigate the effects of sodium pentobarbital overdoses during exsanguination, three groups (6 rats/group) of male and female rats were injected i.p. with 50, 100 and 150 mg/kg of sodium pentobarbital, then carotid exsanguination was performed immediately after loss of consciousness. Hypoxia-inducible factor 1-alpha (Hif1a) and tumor necrosis factor-alpha (Tnfa) mRNA expressions in liver and kidney organs were evaluated. As well as, serum aminotransferase activities (AST&ALT), glucose, urea, creatinine, malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT) levels were determined. The histological alterations in liver, kidney and spleen were studied. It was found that Hif1a and Tnfa were significantly overexpressed in the studied organs and serum AST, glucose, creatinine and urea levels were significantly increased after sodium pentobarbital overdoses (100 and 150 mg/kg) compared to 50 mg/kg dose. Similarly, significant increase in MDA and GSH levels of liver, kidney and spleen were noticed. Results showed gender difference where Hif1a and Tnfa levels were significantly overexpressed at high dose of sodium pentobarbital of liver and kidney organs in female more than male rats. Since euthanasia protocol may influence the physiological variables and affect genes’ expression, it is recommended to avoid sodium pentobarbital overdose during euthanasia as it may interfere with the biochemical, molecular and histological measurements.

Objective evaluate the antiulcer healing effect of echinochrome pigment (Ech 5 and 10 mg/kg) extracted from sea urchin (Paracentrotus lividus). Methods Severe gastric ulceration induced in rats by administration of indomethacin in combination with cold stress (IND + CS) for 2 h. The antiulcer effect of Ech was indicated by determination of gastric juice volume, gastric juice acidity, and ulcer index as well as determination of gastric malondialdhyde (MDA), glutathione (GSH), catalase (CAT), glutathione–S-transferase (GST), superoxide dismutase (SOD), nitric oxide (NO) activities. Moreover, macroscopic and microscopic evaluations of the stomachs were determined. Results The anti-ulcer healing effect of Ech against IND + CS induced oxidative tissue injury was investigated by a significant decrease in MDA level, GST and CAT activities and a significant increase of GSH content, NO level and SOD activity. In addition, Ech treatments (5 mg/kg and 10 mg/kg) reduce gastric lesion area to (73.51% and 75.50%, respectively) with great amelioration of the gastric juice volume and acidity. Also, affirmed by maintaining macroscopic and microscopic gastric mucosal integrity. Conclusions Ech pigments had an insightful effect against peptic ulcer-induced oxidative stress in rats, as it alleviates the alterations in gastric acidity and ulcer index as well as the oxidative stress markers.

Components of bedding might interact with experimental treatments and affect the outcome of various experiments. Here we studied the biochemical effects of 3 rodent bedding materials that are commonly used in Egypt. Male and female rats and mice were assigned randomly into 4 single-sex and single-species groups (10 animals per group). Three types of bedding-rice straw, wheat straw, and pine wood shavings-were evaluated. After 4 wk, animals were euthanized, and biochemical parameters were measured. In male and female rats given wood shavings, serum ALT activity and malondialdehyde concentration increased whereas catalase activity decreased compared with levels in the wheat straw group. In contrast, ALT activity and malondialdehyde concentrations decreased but CAT activity increased in rats housed on rice straw compared with wheat straw. Serum AST and ALT activities increased in male and female mice exposed to rice straw, whereas the malondialdehyde concentration increased and catalase decreased in the wood shavings group relative to the wheat straw group. In mice exposed to wheat straw, AST and ALT activities and malondialdehyde concentrations decreased and CAT activity increased compared with the other groups. Because our results showed that exposure to wood shavings affects some biochemical parameters of rats and mice, we do not recommend its use as laboratory animal bedding. We consider that, of the materials tested, rice straw bedding is the best bedding material for rats, whereas wheat straw is best for mice.

Objective The present investigation explored the therapeutic potential effect of Sepia officinalis body tissue (SOBT) and Sepia officinalis polysaccharide (SOP) extracts, in animal model of sepsis [induced by cecal ligation and puncture (CLP)]. Materials and methods Experimental animals were divided into 4 groups, Group 1: Sham control rats. Group 2: Septic rats. Group 3: Septic rats treated with methanolic extract of Sepia officinalis body tissue (SOBT) (500 mg/kg body weight) for 2 days. Group 4: Septic rats treated with Sepia officinalis polysaccharide (SOP) extract (200 mg/kg body weight) for 2 days. Results The antioxidant activity of SOBT and SOP was proven by DPPH test. CLP-induced liver and kidney toxicities showed by an increase in the ALAT, ASAT, γGT, ALP, creatinine, BUN and uric acid concentrations in serum. Moreover, CLP-induced oxidative stress in liver and kidney evidenced by the increase of MDA levels, decrease in GSH concentrations and decrease in the enzymatic antioxidants (SOD, CAT, GST). In addition, CLP caused decrease in CYP1A2 content in liver. Conclusions Our findings demonstrate the therapeutic efficacy of SOBT and SOP in liver and kidney disorders. Therefore this study suggests that SOBT and SOP could be a potential therapeutic agents for sepsis treatment.

The present study aims to evaluate the possible protective role of polysaccharides extracted from the Egyptian mango Mangifera indica L. (MPS) and/or silymarine against cyclophosphamide (CP) toxicity in male albino rats. The MPS and/or silymarin significantly decreased the activities of serum ASAT and ALAT. However, MPS (1000 mg/kg) normalized their activities towards the normal levels recording 28.75 and 78.75 U/ml respectively. The recorded data also showed the antioxidant effect of MPS by decreasing the level of malondialdehyde (MDA) and increasing the level of reduced glutathione (GSH) as well as normalized the activities of the antioxidant enzyme GST and SOD. Histopathological examinations also confirmed the protective efficacy of MPS against liver toxicity of CP. In conclusion, the recorded results of the present study support the protective role of MPS and/or silymarin against CP-induced hepatic damage.

Multidrug resistance (MDR) is a critical hindrance to the success of cancer chemotherapy. The main thing responsible for MDR phenotypes are plasma-membranes associated with adenosine triphosphate (ATP) Binding Cassette (ABC) drug efflux transporters, such as the P-glycoprotein (Pgp) transporter that has the broadest spectrum of substrates. Curcumin (CURC) is a Pgp inhibitor, but it is poorly soluble and bioavailable. To overcome these limitations, we validated the efficacy and safety of CURC, loaded in biocompatible solid lipid nanoparticles (SLNs), with or without chitosan coating, with the goal of increasing the stability, homogeneous water dispersibility, and cellular uptake. Both CURC-loaded SLNs were 5&ndash, 10-fold more effective than free CURC in increasing the intracellular retention and toxicity of doxorubicin in Pgp-expressing triple negative breast cancer (TNBC). The effect was due to the decrease of intracellular reactive oxygen species, consequent inhibition of the Akt/IKK&alpha, &beta, /NF-kB axis, and reduced transcriptional activation of the Pgp promoter by p65/p50 NF-kB. CURC-loaded SLNs also effectively rescued the sensitivity to doxorubicin against drug-resistant TNBC tumors, without signs of systemic toxicity. These results suggest that the combination therapy, based on CURC-loaded SLNs and doxorubicin, is an effective and safe approach to overcome the Pgp-mediated chemoresistance in TNBC.

Objective: To explore the efficacy of earthworm’s coelomic fluid against gentamicin-induced hepatic and renal toxicity in rats. Methods: The animals were divided randomly into three groups (n = 6 per group): control, gentamicin, and Allolobophora caliginosa coelomic fluid-treated groups. Toxicity was established after injection of gentamicin daily for 8 days at a dose of 100 mg/kg. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total proteins, albumin, creatinine, urea, uric acid, malondialdehyde, glutathione, catalase and histopathology of tissues were investigated in the study. Results: Allolobophora caliginosa coelomic fluid significantly decreased urea, creatinine, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and malondialdehyde levels while significantly increasing levels of total proteins, albumin, glutathione and catalase. The histopathological investigation showed partial restoration of renal and hepatic architecture. Conclusions: This study shows the potency of Allolobophora caliginosa coelomic fluid in improving the biochemical and histopathological changes induced by gentamicin in the liver and kidney of the rats.

Background Drug-induced hepatotoxicity is an extremely widespread condition and is responsible for a variety of pathological effects on the liver. It was reported that hepatotoxicity induced by angiotensin converting enzyme inhibitors (ACEIs) is cholestasis mediated hepatitis. Bradykinin-potentiating factor (BPF) is one of the natural ACEIs. Although prolonged treatment with ACEIs provides protection against liver injury, the effect of short-term treatment with ACEIs has not been fully elucidated before. Thereby, the present study sought to determine if transient ACE inhibition may exacerbate the hepatotoxicity caused by bile duct ligation (BDL) in rats. Methods Twenty one Wistar rats were divided into 3 groups: Sham-operated group, bile duct ligated (BDL) rats, and BDL rats treated for short-term with BPF (1 μg/kg body weight) day after day for one week and biochemical parameters were measured. Also, we assessed expression level of ACE1 and detection of hepatotoxicity in the liver tissues of different groups. Results There was a significant increase in liver enzymes, bilirubin levels, and oxidative stress in the BDL group after treatment with BPF as compared to BDL group. We found overexpression of ACE1 gene in BDL group compared to BPF and Sham-operated control group. Histopathological examination of liver treated with BPF showed severe degeneration hepatic architecture and hepatocytes as compared to BDL group. Collagen deposition increased after BPF treatment as compared to BDL groups. Conclusion The present investigation suggests and recommends that short- term ACE inhibition pathway potentiates liver fibrosis during cholestasis disease.

The implementation of principles and guidelines that govern the various areas of research in an educational institution is one of the key factors in international recognition of its research integrity and value. The privilege of conducting research using animal subjects requires adherence to international regulations and standards governing the humane care and use of laboratory animals. The IACUC at our university deemed it critical to have an animal care and use training program to raise researchers’ understanding and knowledge. Our IACUC recently designed a training program in the principles of laboratory animal science and the ethical issues involved in animal use. The present study aimed to measure the effect of such training on scientists’ attitudes and practice. During 4 successive training courses, the participants (n = 100; 72% women and 28% men) were surveyed twice through self-administered questionnaire—before starting and after completing the course. Questions focused on ethical consideration for care and use of animals in research, ethical committees, international guidelines for humane care of animals, and 3Rs concepts and their interpretation. The results revealed that the scientists’ knowledge and awareness increased effectively after the completion of the training courses. They understood the 3Rs concepts of replacement, reduction, and refinement; recognized the importance of standardization of animal handling on scientific results; and were able to distinguish between different ethical committees and their roles. Overall, training leads to standardization of animal care and use practices that are vital for the reproducibility of results fundamental to quality scientific research.

Holothuria arenicola is the most important and abundant sea cucumber species in the Mediterranean Sea on the Egyptian coast. This work aimed to investigate the prophylactic and the curative effects of H. arenicola extract HaE (200 mg/kg) on gastric mucosal damage following indomethacin and cold stress in healthy rats. Sixty-four rats were randomly divided into four main groups. Rats of the first group (8 rats/group) were administered distilled water orally (control group), rats of the second group (8 rats/group) were administered single oral dose of indomethacin (150 mg/kg) and exposed to cold stress (4 ± 1 °C) for 30 min to induce gastric ulcer (GU) model (ulcer group), rats of the third group, prophylactic group (24 rats/group) were treated with HaE and/or ranitidine (RAN) and then exposed to GU and rats of the fourth group, curative group (24 rats/group) were exposed firstly to GU and then treated with HaE and/or RAN. The results clearly indicate that pre-treatment with HaE and/or ranitidine significantly decreases the ulcer index, showing 72.50%, 53.11% and 80.56% ulceration inhibition, respectively. However, post-treatment with HaE and/or ranitidine significantly decreases the ulcer index, showing 51.66%, 62.41% and 67.78% ulceration inhibition, respectively. The results also showed that pre and post-treatment with HaE and/or RAN significantly decreased gastric malondialdehyde (MDA) level and enhanced reduced glutathione (GSH), catalase (CAT), glutathione-S-transferase (GST) and superoxide dismutase (SOD) levels. The results clearly indicate that pre-treatment with HaE is preferable.

The prevalence of antibiotic resistance has resulted in the need for new approaches to be developed to combat the previously easily treatable infections. This work aims to evaluate the antifungal and antioxidant effects of the chitosan, as a new alternative or complementary anti-fungal drug, alone or in combination with amphotericin B against a pathogenic Candida albicans in mice. Eighty neutropenic infected mice were randomly assigned into four main groups (20 mice/group). The 1st group was treated with saline, neutropenic infected (NI group) (IPC group, invasive pulmonary candidiasis), the 2nd group was treated with chitosan (ED 50 ) (CE group), the 3rd group was treated with amphotericin B (150 mg/kg) (AMB group) and the 4th group was treated with chitosan plus amphotericin B (CE + AMB group). Treatment was started at 24 h after fungal inoculation and was administered for 3 consecutive days. All the previous treatments demonstrated notable growth inhibition against a C. albicans isolate as indicated by measuring the mean diameter of the inhibition zone. Compared with IPC group, CE, AMB, and AMB + CE-treated animals had 73%, 87%, and 90% reduction in fungal burden, respectively. Furthermore, treatment with CE and/or AMB for 24 and 72 h significantly decreased MDA, SOD, CAT and NO levels and increased GSH and in the lung tissues as compared with the infected untreated group. In conclusion, CE treatment, with the combination of antifungal therapy, can alleviate oxidative stress and lung injury associated with IPC in neutropenic mice.