Caspase-dependent and -independent suppression of apoptosis by monoHER in Doxorubicin treated cells

Doxorubicin (DOX) is an antitumour agent for different types of cancer, but the dose-related cardiotoxicity limits its clinical use. To prevent this side effect we have developed the flavonoid monohydroxyethylrutoside (monoHER), a promising protective agent, which did not interfere with the antitumour activity of DOX. To obtain more insight in the mechanism underlying the selective protective effects of monoHER, we investigated whether monoHER (1 mM) affects DOX-induced apoptosis in neonatal rat cardiac myocytes (NeRCaMs), human endothelial cells (HUVECs) and the ovarian cancer cell lines A2780 and OVCAR-3. DOX-induced cell death was effectively reduced by monoHER in heart, endothelial and A2780 cells. OVCAR-3 cells were highly resistant to DOX-induced apoptosis. Experiments with the caspase-inhibitor zVAD-fmk showed that DOX-induced apoptosis was caspase-dependent in HUVECs and A2780 cells, whereas caspase-independent mechanisms seem to be important in NeRCaMs. MonoHER suppressed DOX-dependent activation of the mitochondrial apoptotic pathway in normal and A2780 cells as illustrated by p53 accumulation and activation of caspase-9 and -3 cleavage. Thus, monoHER acts by suppressing the activation of molecular mechanisms that mediate either caspase-dependent or -independent cell death. In light of the current work and our previous studies, the use of clinically achievable concentrations of monoHER has no influence on the antitumour activity of DOX whereas higher concentrations as used in the present study could influence the antitumour activity of DOX

Novi steroidni derivati sintetizirani iz 3betha-hidroksiandrosten-17-ona

In this study, we synthesized some new substituted steroidal derivatives using 3betha-hydroxyandrosten-17-one (dehydroepiandrosterone) as starting material. The synthesized steroidal derivatives 1-11 were evaluated for their androgenic-anabolic activities compared to testosterone as positive control. Details of the synthesis, spectroscopic data and toxicity (LD50) of synthesized compounds are reported.U radu je opisana sinteza novih steroidnih derivata 1-11 koristeći 3betha-hidroksiandrosten-17-on (dehidroepiandrosteron) kao početnu supstanciju. Androgeno-anaboličko djelovanje tih spojeva uspoređivano je s djelovanjem testosterona kao pozitivnom kontrolom. Navode se detaljni sintetski postupci, spektroskopska karakterizacija i podaci o toksičnosti (LD50)

DIFFERENT TOPICAL FORMULATIONS OF KETOROLAC TROMETHAMINE FOR ANTI-INFLAMMATORY APPLICATION AND CLINICAL EFFICACY

Ketorolac tromethamine (KT) is considered as a member of NSAIDs that used in treatment of rheumatoid arthritis. The main problems associated with the frequent administration of KT orally could be overcome by alternative routes as topical application. KT was formulated in different topical formulations such as gels, emulgels and creams. Sodium carboxymethylcellulose, carbopol 934 and pluronic F127 were used as polymers. In vitro permeation study through rat skin was carried out. The effect of different KT concentrations and the effect of skin penetration enhancer on the amount of KT permeated were investigated. Anti-inflammatory activity using commercial piroxicam gel for comparison was evaluated. The effectiveness and tolerability of the selected KT gel and piroxicam gel in osteoarthritis patients was also studied. The results obtained showed that, the flux of the drug increased with increasing its initial concentration. Using sodium lauryl sulfate as enhancer resulted in an improvement of KT permeation through rat skin. All formulations had the potential for local applications of KT as anti-inflammatory drug as compared to the control group. There was no significant difference in the efficacy between the selected KT gel and piroxicam gel for osteoarthritis patients. So KT gel may be used as another therapeutic option for the treatment of patients with osteoarthritis

Physiological and Neurobehavioral Disturbances Induced by Al2O3 Nanoparticle Intoxication in Nile Tilapia Fish: Benefits of Dietary Chamomile Essential Oil

Despite the usage of nanoparticles (NPs) is rapidly increasing, several experts have noted the risk of their release into ecosystems and their potential negative impacts on biological systems. However, the available studies on the neurobehavioral impacts of aluminum oxide nanoparticles (Al2O3NPs) on aquatic organisms are little. Hence, this study targeted to ascertain the harmful effects of Al2O3NPs on behavioral characteristics and genotoxic and oxidative damages in Nile tilapia fish. In addition, the beneficial role of chamomile essential oil (CEO) supplementation in reducing these effects was also investigated. In the current study, fish were distributed into 4 equal groups (n = 60 fish per group). The control group was fed a plain diet only, the CEO group received a basic diet complemented with CEO at a level of 2 mg/kg diet, the ALNP group received a basic diet and was exposed to an approximate concentration of 1/10th LC50 of ALNPs nearly 5.08 mg/L, and the combination group (ALNPs/ CEO group) received a basal diet coadministered with ALNPs and CEO at the aforementioned percentages. The findings revealed that O. niloticus exhibit neurobehavioral changes along with changes in the level of GABA, monoamines in the brain tissue, and serum amino acid neurotransmitters, besides a reduction of AChE and Na+/K+-ATPase activities. In addition to brain tissue oxidative damage with upregulation of proinflammatory and stress genes, such as HSP70 and caspase-3, supplementation of CEO significantly reduced the negative impacts of ALNPs. These results showed that CEO has neuroprotective, antioxidant, genoprotective, anti-inflammatory, and antiapoptotic properties in fish that have been exposed to ALNPs. Therefore, we advise its usage as a valuable addition to fish diet

Medical prospects of cryptosporidiosis in vivo control using biofabricated nanoparticles loaded with Cinnamomum camphora extracts by Ulva fasciata

Background and Aim: Global efforts are continuing to develop preparations against cryptosporidiosis. This study aimed to investigate the efficacy of biosynthesized Ulva fasciata loading Cinnamomum camphora oil extract on new zinc oxide nanoparticles (ZnONPs shorten to ZnNPs) and silver nanoparticles (AgNPs) as alternative treatments for Cryptosporidium parvum experimental infection in rats. Materials and Methods: Oil extract was characterized by gas chromatography-mass spectrometry, loaded by U. fasciata on ionic-based ZnO and NPs, and then characterized by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. Biosafety and toxicity were investigated by skin tests. A total of 105 C. parvum oocysts/rat were used (n = 81, 2–3 W, 80–120 g, 9 male rats/group). Oocysts shedding was counted for 21 d. Doses of each preparation in addition to reference drug were administered daily for 7 d, starting on post-infection (PI) day (3). Nitazoxanide (100 mg) was used as the reference drug. After 3 weeks, the rats were sacrificed for postmortem examination and histopathological examination. Two blood samples/rat/group were collected on the 21st day. Ethylenediaminetetraacetic acid blood samples were also used for analysis of biochemistry, hematology, immunology, micronucleus prevalence, and chromosomal abnormalities. Results: C. camphora leaves yielded 28.5 ± 0.3 g/kg oil and 20 phycocompounds were identified. Spherical and rod-shaped particles were detected at 10.47–30.98 nm and 18.83–38.39 nm, respectively. ZnNPs showed the earliest anti-cryptosporidiosis effect during 7–17 d PI. Other hematological, biochemical, immunological, histological, and genotoxicity parameters were significantly fruitful; hence, normalized pathological changes induced by infestation were observed in the NPs treatments groups against the infestation-free and Nitazoxanide treated group. Conclusion: C. camphora, U. fasciata, ZnNPs, and AgNPs have refluxed the pathological effects of infection as well as positively improved host physiological condition by its anticryptosporidial immunostimulant regenerative effects with sufficient ecofriendly properties to be proposed as an alternative to traditional drugs, especially in individuals with medical reactions against chemical commercial drugs

Anti-inflammatory agents and monoHER protect against DOX-induced cardiotoxicity and accumulation of CML in mice

Cardiac damage is the major limiting factor for the clinical use of doxorubicin (DOX). Preclinical studies indicate that inflammatory effects may be involved in DOX-induced cardiotoxicity. Nɛ-(carboxymethyl) lysine (CML) is suggested to be generated subsequent to oxidative stress, including inflammation. Therefore, the aim of this study was to investigate whether CML increased in the heart after DOX and whether anti-inflammatory agents reduced this effect in addition to their possible protection on DOX-induced cardiotoxicity. These effects were compared with those of the potential cardioprotector 7-monohydroxyethylrutoside (monoHER)

A comparative study between catalase gene therapy and the cardioprotector monohydroxyethylrutoside (MonoHER) in protecting against doxorubicin-induced cardiotoxicity in vitro

50) limited the possibility to increase catalase activity more than 3.5-fold, which was not enough to protect infected NeRCaMs against doxorubicin-induced cardiotoxicity and (2) confirms the efficacy of monoHER as a cardioprotector. Thus, the use of monoHER proves more suitable for the prevention of doxorubicin-induced cardiotoxicity than catalase gene transfer employing adenovirus vectors