Oxidative stress is a common mechanism contributing to the initiation and progression of hepatic damage. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present study is to evaluate the efficacy of Holothuria atra extract (HaE) as an antioxidant against 7,12-dimethylbenz[a]anthracene- (DMBA-) induced hepatorenal dysfunction. Experimental animals were divided into two main groups: protective and curative. Each group was then divided into five subgroups pre- or posttreated either with distilled water (DMBA subgroups) or with HaE (200 mg/kg body weight) for seven and fourteen days. Single oral administration of DMBA (15 mg/kg body weight) to Wistar rats resulted in a significant increase in the serum liver enzymes and kidney function's parameters. DMBA increased level of liver malondialdehyde (MDA), decreased levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) in the liver tissue, and induced liver histopathological alterations. Pre- or posttreatment with HaE orally for 14 days significantly reversed the hepatorenal alterations induced following DMBA administration. In conclusion, HaE exhibits good hepatoprotective, curative, and antioxidant potential against DMBA-induced hepatorenal dysfunction in rats that might be due to decreased free radical generation.

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-β/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.

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. Hypoxiainducible 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. In Egypt, rodents are considered the first choice for the majority of animal research and training. Euthanasia of animals is generally performed upon completion of the study or if a humane endpoint has been reached. Last updates of the Canadian Council on Animal Care (CCAC) and American Veterinary Medical Association (AVMA) euthanasia guidelines 1 describe several techniques for successful euthanasia to refine killing methods for rats and other laboratory animals 2. Euthanasia procedures are divided into two main methods; chemical and physical. Ideally, a mechanical method, such as exsanguination, should be implemented after the chemical death. Pentobarbital is an anesthetic agent commonly used in euthanasia. Olsen and Li (2011) reported that sodium pentobarbital is an injectable, fast-acting, central nervous system depressant which acts via GABA receptors to cause a loss of consciousness and cardiovascular depression 3. In the AVMA Guidelines, anesthetic overdose is recommended as an acceptable method of euthanasia. For rodents, overdose of sodium pentobarbital is the most preferable euthanizing agent 4-6. The main reported negative side effects of pentobarbital mono-anesthesia are cardiovascular and respiratory systems depression, decreased arterial blood pressure, peripheral vasodilation, decreased cardiac output and depression of the vasopressor response to hemorrhage 7. Moreover, ...

Freshwater snails are used as sensitive biomarkers of aquatic ecosystem pollution. The potential impacts of zinc oxide nanoparticles (ZnONPs) on aquatic ecosystems have attracted special attention due to their unique properties. The present investigation was designed to evaluate the possible mechanisms of ecotoxicological effects of ZnONPs on freshwater snail Biomphalaria alexandrina. ZnONPs showed molluscicidal activity against B. alexandrina snails, and the LC50 was 145 μg/ml. Two tested concentrations of ZnONPs were selected: The first concentration was equivalent to LC10 (7 μg/ml), and the second was equivalent to LC25 (35 μg/ml). Exposure to ZnONPs (7 and 35 μg/ml) for three consecutive weeks significantly induced malondialdehyde and nitric oxide with concomitant decreases in glutathione and glutathione-S-transferase levels in hemolymph and soft tissues of treated snails. Moreover, ZnONPs elicited a significant decrease in total protein and albumin contents coinciding with enhancement of total lipids and cholesterol levels as well as activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in hemolymph and soft tissues of treated snails. This study highlights the potential ecological implications of ZnONP release in aquatic environments and may serve to encourage regulatory agencies in Egypt to more carefully monitor and regulate the industrial use and disposal of ZnONPs.

The present study aims to evaluate the antitumor, antioxidant and anti-inflammatory activities of two molluscan extracts, Sepia officinalis, ink extract (IE) and Coelatura aegyptiaca extract (CE). The antioxidant activities of both extracts were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging and lipid peroxidation assays. The analgesic effects were evaluated using the writhing, hot plate and formalin tests. Cytotoxicity assay was performed using sulphorhodamine B (SRB) method on hepatocellular carcinoma (HepG2) cell lines. The IE extract exhibited dose dependent radical scavenging activity. The two tested extracts showed inhibition of thiobarbituric acid-reactive substances (TBARAS) at all concentrations, with an IC50 value of 176.77 and 177.23 (µg/ml), respectively. IE and CE extracts showed analgesic action by inhibiting the acetic acid-induced writhing. IE exhibited significant anti-nociceptive actions in mice by increasing the latency period in the hot-plate test. Both extracts significantly decreased the time of paw lickings in both early and late phases. Furthermore, IE and CE showed cytotoxic activities HepG2 cell lines with IC50 value of 67 and 49.24 µg/ml, respectively. In conclusion, IE and CE extracts have antioxidant, anti-inflammatory and cytotoxic properties and can be considered as promising anticancer drugs.