Anthelmintic and therapeutic effects of the biogenic zinc oxide nanoparticles against acute kidney injury induced by Parascaris equorum Infection in rats.

Complications of parasite infections, especially kidney disease, have been linked to poorer outcomes. Acute kidney damage, glomerulonephritis, and tubular dysfunction are the most prevalent renal consequences of Parascaris equorum infection. The purpose of this study was to determine the pharmacological effects of green-produced zinc oxide nanoparticles (ZnO NPs) on P. equorum infection in male Wistar rats. Thirty-six male rats were divided into two groups of 18 each: infected and non-infected. Both groups were separated into three subgroups, each of which received distilled water, 30 mg/kg ZnO NPs, and 60 mg/kg ZnO NPs. After 10 days of ZnO NPs administration, four larvae per gram of kidney tissue were present in the untreated infected group. While, no larvae were present in ZnO NPs (30 mg/kg) treated group, and one larva/g.tissue was present in ZnO NPs (60 mg/kg) treated group compared to untreated infected animals. P. equorum infected rats had increased kidney biomarkers (creatinine, urea, uric acid), malondialdehyde, and nitric oxide, with a significant decrease in their antioxidant systems. On the other hand, infected treated rats with green-produced zinc oxide nanoparticles had a substantial drop in creatinine, urea, uric acid, malondialdehyde, and nitric oxide, as well as a significant rise in their antioxidant systems. P. equorum infection in rats caused severe degenerative and necrotic renal tissues. On the other hand, there were no detectable histopathological alterations in rats treated with ZnO NPs (30, 60 mg/kg) as compared to the infected untreated animals. When compared to infected untreated mice, immunohistochemical examination of nuclear factor-kappa B showed a significant decrease during treatment with ZnO NPs (30, 60 mg/kg). Green-produced zinc oxide nanoparticles are a viable therapeutic strategy for Parascaris equorum infection due to their potent anthelmintic activity, including a significant decrease in larval burden in infected treated rats.

Correction: Anthelmintic and therapeutic effects of the biogenic zinc oxide nanoparticles against acute kidney injury induced by Parascaris equorum Infection in rats.

[This corrects the article DOI: 10.1007/s12639-023-01637-z.].

Guidelines for the establishment and functioning of Animal Ethics Commitees (Institutional Animal Care and Use Committees) in Africa.

Animals are used for scientific purposes across Africa to benefit humans, animals or the environment. Nonetheless, ethical and regulatory oversight remains limited in many parts of the continent. To strengthen this governance framework, the Pan-African Network for Laboratory Animal Science and Ethics brought together experts from 12 African countries to create an Africa-centric practical guide to facilitate the establishment and appropriate functioning of Institutional Animal Ethics Committees across Africa. The Guidelines are based on universal principles for the care and use of sentient animals for scientific purposes, with consideration of the cultural, religious, political and socio-economic diversity in Africa. They focus on 11 key elements, including responsibilities of institutions and of the Institutional Official; composition of the Committee; its responsibilities, functioning and authority; ethical application and review processes; oversight and monitoring of animal care and use and of training and competence; quality assurance; and the roles of other responsible parties. The intent is for African institutions to adopt and adapt the guidelines, aligning with existing national legislation and standards where relevant, thus ensuring incorporation into practice. More broadly, the Guidelines form an essential component of the growing discourse in Africa regarding moral considerations of, and appropriate standards for, the care and use of animals for scientific purposes. The increased establishment of appropriately functioning animal ethics committees and robust ethical review procedures across Africa will enhance research quality and culture, strengthen societal awareness of animals as sentient beings, improve animal well-being, bolster standards of animal care and use, and contribute to sustainable socio-economic development.

Anthelmintic and Hepatoprotective Activities of the Green-Synthesized Zinc Oxide Nanoparticles Against Parascaris equorum Infection in Rats.

MAIN CONCLUSIONS: Green-synthesized zinc oxide nanoparticle is a promising treatment modality against parasitic infection through its powerful anthelmintic, antioxidant, healing promotion, and anti-inflammation effects. BACKGROUND: Nanoparticles have many properties, depending on their size, shape, and morphology, allowing them to interact with microorganisms, plants, and animals. OBJECTIVES: Investigation of the therapeutic effects of green-synthesized zinc oxide nanoparticles (ZnO NPs) on Parascaris equorum infection in rats. METHODS: Thirty-six rats were divided into two divisions: the first division is noninfected groups were allocated into three groups. Group 1: Control, group 2: ZnO NPs (30 mg/kg), and group 3: ZnO NPs (60 mg/kg). The second division is infected groups were allocated into three groups. Group 1: vehicle, group 2: ZnO NPs (30 mg/kg), and group 3: ZnO NPs (60 mg/kg). FINDINGS: Ten days post-infection, two larvae per gram of liver tissue were present in the vehicle group compared to the control group. No larvae were recovered from ZnO NPs (30 mg/kg), and one larva/g.tissue from ZnO NPs (60 mg/kg)-treated groups compared to untreated infected animals. Green-synthesized ZnO NPs caused a significant decrease in liver functions, low-density lipoprotein (LDL), cholesterol, triglycerides, malondialdehyde (MDA), and nitric oxide (NO). While it caused a significant increase in hemoglobin (HB), high-density lipoprotein (HDL), butyrylcholinesterase (BCHE), glutathione (GSH), catalase (CAT), and glutathione S-transferase (GST) in infected treated rats. The histological inflammation and fibroplasia scores showed a significant enhancement during the treatment with ZnO NPs (30, 60 mg/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, 60 mg/kg) compared to the infected untreated animals.

A nano-Liposomal formulation potentiates antioxidant, anti-inflammatory, and fibrinolytic activities of Allolobophora caliginosa coelomic fluid: formulation and characterization.

BACKGROUND: Coelomic fluid, a pharmacologically active compound in earthworms, exhibits a range of biological activities, including antioxidant, anti-inflammatory, and anticancer. However, the biological activities exerted by the coelomic fluid can be restrained by its low bioavailability and stability. Liposomes are progressively utilized as an entrapment system for natural bioactive compounds with poor bioavailability and stability, which could be appropriate for coelomic fluid. Thus, the present study was designed to fabricate, characterize, and evaluate the stability of liposomal formulation for Allolobophora caliginosa coelomic fluid (ACCF) as a natural antioxidant compound. METHODS: The ACCF-liposomes were developed with a subsequent characterization of their physicochemical attributes. The physical stability, ACCF release behavior, and gastrointestinal stability were evaluated in vitro. The biological activities of ACCF and its liposomal formulation were also determined. RESULTS: The liposomal formulation of ACCF had a steady characteristic absorption band at 201 nm and a transmittance of 99.20 ± 0.10%. Its average hydrodynamic particle size was 98 nm, with a PDI of 0.29 ± 0.04 and a negative zeta potential (-38.66 ± 0.33mV). TEM further confirmed the formation of vesicular, spherical nano-liposomes with unilamellar configuration. Additionally, a remarkable entrapment efficiency percent (77.58 ± 0.82%) with a permeability rate equal to 3.20 ± 0.31% and a high retention rate (54.16 ± 2.20%) for ACCF-liposomes were observed. The Fourier transform infrared spectroscopy (FTIR) result demonstrated that ACCF successfully entrapped inside liposomes. The ACCF-liposomes exhibited a slow and controlled ACCF release in vitro. Regarding stability studies, the liposomal formulation enhanced the stability of ACCF during storage and at different pH. Furthermore, ACCF-liposomes are highly stable in intestinal digestion conditions comparable to gastric digestion. The current study disclosed that liposomal formulation potentiates the biological activities of ACCF, especially antioxidant, anti-inflammatory, and thrombolytic activities. CONCLUSION: These promising results offer a novel approach to increasing the bioaccessibility of ACCF, which may be crucial for the development of pharmaceuticals and nutraceutical-enriched functional foods.

Allolobophora caliginosa coelomic fluid and extract alleviate glucocorticoid-induced osteoporosis in mice by suppressing oxidative stress and regulating osteoblastic/osteoclastic-related markers.

Allolobophora calignosa (Ac) is a folk medicine for millennia, as it possesses many biological activities. This study aimed to investigate the chemo-preventive activity of A.calignosa coelomic fluid (AcCF) and A.calignosa extract (AcE) on glucocorticoid-induced osteoporosis (GIOP) in mice. Characterization and in vitro biological activity of AcE and AcCF has been assessed. Male CD-1 mice were subcutaneously received dexamethasone (DEX) (1 mg/kg, 5 times/week) and concurrently intraperitoneally treated with either AcCF (20 mg/kg) or AcE (45 mg/kg) every other day for 28 days. Serum and bone homogenates were subjected for qPCR and biochemical analysis. AcE and AcCF treatment significantly increased bone mineral density (BMD), bone mineral content (BMC), calcium (Ca), phosphorus (P), and calcitonin levels, whereas activity of serum alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), serum acidic phosphatase (ACP), bone acidic phosphatase (BACP) and parathyroid hormone (PTH) levels were significantly reduced compare with untreated GIOP mice. Treatment with AcE and AcCF modulates oxidative stress and downregulated Rank and Mmp9 expression, as well as increased glycosaminoglycan content in the organic bone matrix, resulting in osteoclastogenesis inhibition. Overall, AcCF and AcE show a chemo-preventive activity against GIOP by inhibiting oxidative stress and regulating expression and/or activity of osteoblast/osteoclast-related markers.

Development of a Novel Pomegranate Polysaccharide Nanoemulsion Formulation with Anti-Inflammatory, Antioxidant, and Antitumor Properties.

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.

Sustainable education and training in laboratory animal science and ethics in low- and middle-income countries in Africa - challenges, successes, and the way forward.

Despite the recognised need for education and training in laboratory animal science (LAS) and ethics in Africa, access to such opportunities has historically been limited. To address this, the Pan-African Network for Laboratory Animal Science and Ethics (PAN-LASE) was established to pioneer a support network for the development of education and training in LAS and ethics across the African continent.In the 4.5 years since the establishment of PAN-LASE, 3635 individuals from 28 African countries have participated in our educational activities. Returning to their home institutions, they have both established and strengthened institutional and regional hubs of knowledge and competence across the continent. Additionally, PAN-LASE supported the development of guidelines for establishment of institutional Animal Ethics Committees, a critical step in the implementation of ethical review processes across the continent, and in enhancing animal welfare and scientific research standards.Key challenges and opportunities for PAN-LASE going forward include the formalisation of the network; the sustainability of education and training programmes; implementation of effective hub-and-spoke models of educational provision; strengthening governance frameworks at institutional, national and regional levels; and the availability of Africa-centric open access educational resources.Our activities are enhancing animal welfare and the quality of animal research undertaken across Africa, enabling African researchers to undertake world-leading research to offer solutions to the challenges facing the continent. The challenges, successes and the lessons learnt from PAN-LASE's journey are applicable to other low- and middle-income countries across the world seeking to enhance animal welfare, research ethics and ethical review in their own country or region.

In vitro anti-Toxocara vitulorum effect of silver nanoparticles.

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.

Histopathological and immunohistochemical study of antiosteoporotic efficacy of the earthworm Allolobophora caliginosa extract in orchiectomized rats / Estudio histopatológico e inmunohistoquímico de la eficacia antiosteoporótica del extracto de lombriz de tierra Allolobophora caliginosa en ratas orquiectomizadas

SUMMARY: Osteoporosis is a bone condition marked by a loss of bone mass and a disruption of bone microarchitecture. Men lose bone density as they age, resulting in brittle bones. The loss of free testosterone is one of the key factors. The objective of present study was to evaluate Allolobophora caliginosa extract (AcE) for its anti-osteoporotic and antiapoptotic activity in orchiotomized rat model at two different dose levels. Twenty eight male rats were divided into two groups. The first group represented sham operated rats while the second group underwent bilateral orchidectomy (OCX). After one week of recovery from orchidectomy surgery, the second group was randomly subdivided into 3 subgroups. The first OCX subgroup was administered orally distilled water daily for 10 weeks. The other two OCX subgroups were administered AcE (100 or200 mg/kg body weight/day) orally for 10 weeks. Orchiectomy induces remarkable loss of the cortical as well as trabecular bone loss; which, could be counterbalanced by Allolobophora caliginosa extract (AcE) that prevented cortical as well as trabecular bone loss. Allolobophora caliginosa extract (AcE) at Dose 200 mg/kg/day was found to be effective at a highly significant level in osteoporotic bone, as determined by histological images and immunohistochemical study, where Dose (100 mg/kg/day) was found to be moderately significant.In the present study, it is suggested that AcE may inhibit steroid-induced osteoblasts apoptosis, potentially via upregulation of Bcl-2 and downregulation of caspase-3. Allolobophora caliginosa extract demonstrates anti-apoptotic and anti-oxidant properties. Therefore, AcE may be used for the prevention of steroid-induced bone damage.

RESUMEN: La osteoporosis es una afección ósea caracterizada por una pérdida de masa ósea y una alteración de la microarquitectura ósea. Los hombres pierden densidad ósea a medida que envejecen, lo que resulta en huesos quebradizos. La pérdida de testosterona libre es factor clave en este proceso. El objetivo del presente estudio fue evaluar el extracto de Allolobophora caliginosa (AcE) debido a su actividad antiosteoporótica y antiapoptótica en un modelo de rata orquiectomizadas con dos niveles de dosis diferentes. Se dividieron veintiocho ratas macho en dos grupos. El primer grupo incluyó ratas con operación simulada, mientras que el segundo grupo se sometió a orquidectomía bilateral (OCX). Después de una semana de recuperación de la orquidectomía, el segundo grupo fue subdividido en 3 subgrupos. Al primer subgrupo de OCX se administró diariamente agua destilada por vía oral durante 10 semanas. Los otros dos subgrupos de OCX se administraron por vía oral AcE (100 o 200 mg / kg de peso corporal / día) durante 10 semanas. La orquidectomía induce una pérdida notable del hueso cortical y trabecular; el cual podría ser contrarrestado por el extracto de Allolobophora caliginosa (AcE) que previno la pérdida de hueso tanto cortical como trabecular visualizado en imágenes histológicas y estudio inmuno- histoquímico, donde se encontró que la dosis (100 mg / kg / día) era moderadamente significativa. En el presente estudio, se sugiere que la AcE puede inhibir la apoptosis de los osteoblastos inducida por esteroides, potencialmente a través de la regulación al alza de Bcl 2 y la regulación a la baja de caspasa 3. El extracto de Allolobophora caliginosa demuestra propiedades anti apoptóticas y antioxidantes. Por lo tanto, AcE puede usarse para la prevención del daño óseo inducido por esteroides.

Echinochrome pigment extracted from sea urchin suppress the bacterial activity, inflammation, nociception, and oxidative stress resulted in the inhibition of renal injury in septic rats.

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.

Glabratephrin reverses doxorubicin resistance in triple negative breast cancer by inhibiting P-glycoprotein.

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.

Culture of Care Enhancement in Egypt: The Impact of Laboratory Animal Science Training on Participants' Attitudes.

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.

Silver/chitosan nanocomposites induce physiological and histological changes in freshwater bivalve.

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.

Antitumor activity of saponin isolated from the sea cucumber, holothuria arenicola against ehrlich ascites carcinoma cells in swiss albino mice.

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.

Freshwater Clam as a Potential Bioindicator for Silver/Saponin Nanocomposites Toxicity.

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.

Protective effect of Echinochrome against intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats / Efeito protetor de Echinochrome contra colestase intra-hepática induzida por isotiocianato de alfa-naftilo em ratos

Abstract 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.

Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells.

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 5-10-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/IKKα-ß/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.

Sodium pentobarbital dosages for exsanguination affect biochemical, molecular and histological measurements in rats.

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.