Aurothiomalate-Based Drugs as Potentially Novel Agents Against Leishmania major: A Mini Review.

PURPOSE: Leishmaniasis is a major public health problem worldwide in many parts of the world. Current anti-leishmanial drugs have only limited clinical efficacy. Aurothiomalate derivatives are useful for treating rheumatoid arthritis, but have emerged as a promising therapeutic candidate for leishmaniasis. This paper gives a review of the literature about the usefulness of aurothiomalate derivatives against leishmaniasis. METHODS: In this study, we reviewed the proposed mechanisms of action of aurothiomalate and related compounds on the metabolism of L. major and collected data by searching relevant articles. RESULTS: Aurothiomalate-based drugs could be effective against leishmaniasis through two direct and indirect mechanisms: first, cytotoxic effects on parasites via thiomalate's false substrate role in the citric acid cycle against malate; and second, immunosuppressive and anti-inflammatory effects of aurothiomalate derivatives with prostaglandin production inhibitory effects. CONCLUSIONS: The current study documented that aurothiomalate-based drugs could be effective against leishmaniasis through two direct and indirect mechanisms of action. Gold thiomalate as a promising hit should be evaluated against L. major in vitro and in vivo conditions in the future.

Peganum harmala and Nigella sativa: anti-leishmanial activity against Leishmania major promastigotes and amastigotes: in vitro and ex vivo experiment.

Leishmaniosis is one of the most important vectors borne disease that is endemic in tropical and subtropical areas. There are many approved treatment for different types of leishmaniosis but all are with some adverse side effects that limited its uses. Here, we attempt to evaluate in vitro and ex vivo anti-leishmanial activities of Peganum harmala (P. harmala) and N. sativa (Nigella sativa) on promastigotes and amastigotes of L. major. The plants were extracted by maceration method and prepared in concentrations of 7.8, 3.9, 1.9, and 0.9 µg. L. major were cultured in RPMI-1640 medium alone and in J774 cell line separately. The extracts at different concentrations were assessed against promastigote (in vitro assay) and amastigotes (ex vivo assay) of L. major for 72 h at 22 and 37°C, respectively. In current work, N. sativa at highest concentration (7.8 µg/ml) showed 54.4 and 60% anti-leishmanial activity with IC50 of 5.3 and 3.278 µg/ml, respectively. Also, P. harmala at highest concentration (7.8 µg/ml) showed 68.9 and 58.6% antileishmanial activity with IC50 of 2.4 µg/ml for both of them, respectively. The SI value was 38.22 for N. sativa, 25.9 for P. harmala, 19.4 for Amphotericin B, and 16.33 for Glucantime. The results of our study indicated that N. sativa and P. harmala are effective against L. major promastigotes and amastigotes and could be consider as an alternative treatments for leishmaniosis. Therefore, it is recommended that further studies be performed to confirm the efficacy and evaluate the toxicity of the herbal extracts.

Highly Concentrated Multifunctional Silver Nanoparticle Fabrication through Green Reduction of Silver Ions in Terms of Mechanics and Therapeutic Potentials.

BACKGROUND: Green synthesis of silver nanoparticles (AgNPs) is limited to produce AgNPs with only relatively low concentrations, and is unsuitable for large-scale productions. The use of Myrtus communis (MC) leaf methanolic extract (rich in hydrolyzable tannins) has been recommended to resolve the issues related to the aggregation of nanoparticles at high concentrations of silver ions with added facet of antioxidant properties. METHODS: The produced highly concentrated MC-AgNPs were characterized by using imaging and spectroscopic methods. Subsequently, antioxidant, anticancer and antifungal activities of the nanoparticles were evaluated. RESULTS: The thermogravimetric analysis and energy dispersive spectroscopy quantitative results suggested that the nanoparticles are biphasic in nature (bio-molecule + Ag0) and layered in structure, suggesting the formation of nanoparticles through a different mechanism than those described in the literature. MC-AgNPs showed greater scavenging activity of nitric oxide and iron (II) chelating ability than the extract. It also showed good reducing power compared to the standard antioxidant. Remarkable anticancer activity of MC-AgNPs (IC50 = 5.99µg/mL) was found against HCT-116 (human colon carcinoma) cell lines after 24h exposure with a therapeutic index value 2-fold higher than the therapeutic index of standard doxorubicin. Furthermore, distinct antifungal activity (MIC = 4µg/mL) was found against Candida krusei. CONCLUSION: The current method outperforms the existing methods because it produces a large amount of multifunctional nanoscale hybrid materials more efficiently using natural sources; thus, it may be used for diverse biomedical applications.

Engineered Silver Nanoparticles, A New Nanoweapon Against Cancer.

New modifications in nanoparticles changed their applications obviously. Green synthesis of nanoparticles and their biomedical utilizations have been the focus of increasing attention in recent years. Silver nanoparticles (AgNPs) demonstrated surprising effects and many advantageous features for cancer therapy. Investigations indicated the anticancer activity of AgNPs in different ways, comprising cell cycle arrest, DNA damaging and apoptosis, alteration of P53 function, up/down regulation of some important cytokine genes and so on. But some key inquiries like the ability to control the accidental effects of AgNPs, or encompassing process for parcels, which reduces the toxicological profile of nanoparticles, still remained. "Green synthesis" of nanoparticles has been shown to be a kind of approach to resolve the toxicity amounts in a range of 10-18 times. Using distinctive properties of this approach, i.e. as green synthesized silver nanoparticles (G-AgNPs), in order to raise potential therapeutic efficacy, even up to two-fold higher than cis-platin, is going to play a crucial role in cancer treatment and could be considered as a new insight in this field. The current review focuses on the antioxidant activity of G-AgNPs and potential impacts on cancer cells.

Green synthesis of safe zero valent iron nanoparticles by Myrtus communis leaf extract as an effective agent for reducing excessive iron in iron-overloaded mice, a thalassemia model.

Green synthesis of Myrtus communis-Zero Valent Iron Nanoparticles (MC-ZVINs) was carried out in an alkaline environment. These nanoparticles were introduced for testing in vivo iron chelation in an iron-overload thalassemia model in mice. The MC-ZVINs were characterized by the use of imaging (electron microscopy) and spectroscopic (UV-vis and infrared absorption, dynamic light scattering and X-ray diffraction) methods. These methods demonstrated that some polyphenols are bound to the surfaces of the MC-ZVINs as a capping/stabilizing agent. The MC-ZVINs and defroxamine were injected 5 times a week over 4 weeks. The total iron and Fe3+ content of serum was determined by microwave plasma-atomic emission spectroscopy and an Fe3+ ion measuring kit respectively and liver enzyme levels were evaluated with an auto-analyzer. Morphological changes of the liver were examined by haematoxylin and eosin and Prussian blue staining. Additionally, the bioactivity of the iron nanoparticles was checked by DPPH and nitric oxide radical scavenging activity, reducing power and iron (Fe2+) chelating ability. Iron-overloaded mice treated with the MC-ZVINs, indicated a drastic reduction in serum iron content when compared with the control groups and those treated with defroxamine. MC-ZVINs exhibit satisfactory potency to chelate excessive iron in mice. The data collected in this study will be helpful for selecting the most appropriate operational conditions for synthesizing green ZVINs in biomedical applications.

Determination of trace elements level of pikeperch collected from the Caspian Sea.

Toxic and essential elements levels (chromium, copper, iron, manganese, nickel, lead, cadmium, and zinc) have been determined in the brain, heart, liver, gill, gonads, spleen, bile and muscle of S. lucioperca, collected from the Caspian Sea by employing Flame- Atomic absorption spectrometry. Results indicated that nearly all of the toxic metals concentrations (nickel, lead and cadmium) in tissues were higher than limits for fish suggested by Food and Agricultural Organization, World Health Organization and European Union. Lead was higher in spleen than other tissues. Levels of essential metals (iron, copper, zinc and manganese) were below the limits suggested by European Union and Food and Agricultural Organization/World Health Organization and Turkish Food Codex for fish. Iron distribution pattern in tissues was in the following order: heart (88.67 ± 2.74 µg g(-1) wet wt) > spleen (70.96 ± 2.05 µg g(-1) wet wt) > bile (29.35 ± 0.94 µg g(-1) wet wt) > brain (14.29 ± 0.51 µg g(-1) wet wt) > liver (8.57 ± 0.29 µg g(-1) wet wt) > gill (3.20 ± 0.14 µg g(-1) wet wt) > red (2.79 ± 0.11 µg g(-1) wet wt) and white muscles (2.79 ± 0.09 µg g(-1) wet wt) > gonads (2.57 ± 0.07 µg g(-1) wet wt).

Cytoprotective effects of curcumin on sodium fluoride-induced intoxication in rat erythrocytes.

Curcumin is well known for its potent antioxidant activity. The result of numerous studies showed that antioxidants can protect against fluoride-induced toxicity. In the present study, protective effects of curcumin against sodium fluoride-induced toxicity in rat erythrocytes were evaluated. Curcumin (10 and 20 mg/kg) and vitamin C (10 mg/kg) were administrated intraperitoneally for 1 week followed by sodium fluoride (600 ppm) treatment for next week. Erythrocytes were isolated and superoxide dismutase and catalase activities as well as the levels of reduced glutathione, and lipid peroxidation were measured. The level of malondialdehyde in sodium fluoride treated rats (595.13 ± 20.23 nmol/g Hb) increased compared to the normal rats (315.44 ± 9.76 nmol/g Hb). Animals which were pretreated with curcumin at 20 mg/kg for 1 week prior to sodium fluoride intoxication showed significant reduction in the malondialdehyde level (320.22 ± 9.28 nmol/g Hb). Also, pretreated with curcumin (20 mg/kg) and vitamin C restored the superoxide dismutase and catalase activities and modified the level of reduced glutathione compared with control group (p > 0.01).

Protective effects of curcumin against sodium fluoride-induced toxicity in rat kidneys.

In the present study, the protective effect of curcumin against sodium fluoride-induced nephrotoxicity was evaluated in rats. Renal injury was induced by daily administration of 600 ppm sodium fluoride in drinking water for 1 week. One week before the administration of fluoride, the animals selected as study group were given curcumin (10 and 20 mg/kg body weight, intraperitoneally). After 1 week, lipid peroxidation level, activities of superoxide dismutase, catalase, and level of glutathione in kidney homogenate were measured. Blood serum samples were examined for creatinine, serum urea, and blood urea nitrogen levels. Another group of rats received vitamin C (10 mg/kg) as standard antioxidant. The results show that curcumin and vitamin C treatment prior to fluoride administration normalized the levels of serum creatinine, serum urea, and blood urea nitrogen. Moreover, curcumin and vitamin C administrations prevented the antioxidant enzyme decreasing and lipid peroxidation levels imbalance. In conclusion, curcumin treatment at the doses of 10 and 20 mg/kg (intraperitoneally) showed significant nephroprotective effects.

Determination of trace element level in different tissues of the leaping mullet (Liza saliens, Mugilidae) collected from Caspian Sea.

The concentrations of Cr, Cu, Fe, Mn, Ni, Pb, Cd, and Zn were determined in the brain, heart, liver, gill, gonad, spleen, kidney, and red and white muscles of Liza saliens (leaping mullet). Trace element levels in fish samples were analyzed by flame atomic absorption spectrometry. Among the non-essential metals, the levels of Ni and Pb in the tissues were higher than limits for fish proposed by FAO/WHO, EU, and TFC. Generally, the levels of the non-essential metals were much higher than those of manganese in the red and white muscles. Fe distribution pattern in tissues was in order of spleen > liver > heart > gill > brain > kidney > gonad > red muscle > white muscle. Red muscle was not within the safe limits for human consumption because non-essential metal (Ni, Pb) contents were higher than standard limits.

Trace element level in different tissues of Rutilus frisii kutum collected from Tajan River, Iran.

Tajan River is among the most significant rivers of the Caspian Sea water basin. In this study, the concentration of Cr, Cu, Fe, Mn, Ni, Pb, Cd, and Zn were determined in brain, heart, liver, gill, bile, and muscle of Rutilus frisii kutum which has great economic value in the Mazandaran state. Trace element levels in fish samples were analyzed by means of atomic absorption spectrometry. Nearly all non-essential metals levels (Ni, Pb, Cd) detected in tissues were higher than limits for fish proposed by FAO/WHO, EU, and TFC. Generally, non-essential metals (Ni, Pb) were so much higher in muscle than the essential metals (Cu, Zn, and Mn) except Fe, which was higher than other metals in nearly all parts, except in gills. Fe distribution pattern in tissues was in order of heart>brain>liver>muscle>bile>gill. Distribution patterns of metal concentrations in the muscle of fish as a main edible part followed the sequence: Fe>Pb>Ni>Cu>Mn>Zn>Cd.