Ocoxin as a complement to first line treatments in cancer.

Chemotherapy and radiotherapy are the most frequent treatment for patients suffering from malignant progression of cancer. Even though new treatments are now being implemented, administration of these chemotherapeutic agents remains as the first line option in many tumor types. However, the secondary effects of these compounds represent one of the main reasons cancer patients lose life quality during disease progression. Recent data suggests that Ocoxin, a plant extract and natural compound based nutritional complement rich in antioxidants and anti-inflammatory mediators exerts a positive effect in patients receiving chemotherapy and radiotherapy. This mixture attenuates the chemotherapy and radiotherapy-related side effects such as radiation-induced skin burns and mucositis, chemotherapy-related diarrhea, hepatic toxicity and blood-infection. Moreover, it has been proven to be effective as anticancer agent in different tumor models both in vitro and in vivo, potentiating the cytotoxic effect of several chemotherapy compounds such as Lapatinib, Gemcitabine, Paclitaxel, Sorafenib and Irinotecan. The aim of this review is to put some light on the potential of this nutritional mixture as an anticancer agent and complement for the standard chemotherapy routine.

Biodistribution and acute toxicity of cadmium-free quantum dots with different surface functional groups in mice following intratracheal inhalation.

Indium phosphide/zinc sulfate (InP/ZnS) quantum dots (QDs) are presumed to be less hazardous than those that contain cadmium. However, the toxicological profile has not been established. The present study investigated the acute toxicity of InP/ZnS QDs with different surface modifications (COOH, NH2, and OH) in mice after pulmonary aerosol inhalation. InP/ZnS QDs were able to pass through the blood-gas barrier and enter the circulation, and subsequently accumulated in major organs. No obvious changes were observed in the body weight or major organ coefficients. Red blood cell counts and platelet-related indicators were in the normal range, but the proportion of white blood cells was altered. The InP/ZnS QDs caused varying degrees of changes in some serum markers, but no histopathological abnormalities related to InP/ZnS QDs treatment was observed in major organs except that hyperemia in alveolar septa was found in lung sections. These results suggested that the effects of respiratory exposure to InP/ZnS QDs on the lungs need to be fully considered in future biomedical application although the overall toxicity of quantum dots is relatively low.

The bioavailability of different zinc compounds used as human dietary supplements in rat prostate: a comparative study.

The normal human prostate accumulates the highest levels of zinc (Zn) of any soft tissue in the body. The pool of zinc available to the body is known to significantly decrease with age. It is suggested that dietary Zn supplementation protects against oxidative damage and reduces the risk of cancer. Zinc sulfate and zinc gluconate were the most frequently mentioned in per os administration in studies on Zn supplementation. The major aim of the study was to compare the bioavailability of different Zn compounds (sulfate, gluconate and citrate) in the prostate after their daily administration to male rats at three different doses (3.0; 15.0; and 50.0 mg Zn/kg b.w.) for 30 days. The results show that bioavailability in the prostate differs significantly between individual zinc preparations. A significantly elevated Zn concentration in the dorso-lateral lobe of the prostate, compared to controls, was found in the rats supplemented with two compounds only: zinc gluconate and zinc citrate. However, after administration of zinc gluconate, this effect occurred even at the lowest dose. The lowest zinc bioavailability in the prostate was found in the rats administered zinc sulfate: no significant Zn increase was seen in particular zones of the prostate. To sum up, the use of zinc gluconate is worth considering as a possible means of zinc supplementation in men.

Preventive effects of selenium yeast, chromium picolinate, zinc sulfate and their combination on oxidative stress, inflammation, impaired angiogenesis and atherogenesis in myocardial infarction in rats.

PURPOSE: Accumulating evidences suggest a critical role of trace metal dyshemostasis in oxidative stress and cardiac dysfunction after myocardial infarction (MI). This study investigated the cardioprotective effects of selenium yeast (Se), chromium picolinate Cr(pic)3, zinc sulfate (Zn) and their combination on isoproterenol (ISO)-induced MI. METHODS: Rats were divided into six groups: normal control, ISO control, Se-pretreated (0.1 mg/kg), Cr(pic)3-pretreated (400 µg/kg), Zn-pretreated (30 mg/kg) and metal combination-pretreated groups. All metals were administered for 28 days and at the 27th day, MI was induced by subcutaneous injection of ISO (85 mg/kg) once for two consecutive days. RESULTS: ISO control group showed hyperlipidemia, elevation of cardiac biomarkers and lipid peroxidation and increased immunostaining of p47 phox NADPH oxidase subunit in addition to decreased levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Cardiac levels of tumor necrosis factor-α (TNF-α) were increased, while vascular endothelial growth factor (VEGF, the major angiogenic factor) was decreased. Pretreatment with Se normalized the cardiac enzymes, lipid peroxidation, GSH, SOD, CAT, GPx, TNF-α and VEGF (P<0.001) and reduced the immunostaining of p47 phox subunit. However, Se failed to correct the dyslipidemia. Cr(pic)3 significantly improved lipid profile (P<0.001) and all other biochemical deviations except for VEGF. Zn, but to lesser extent, reduced the oxidative damage and TNF-α levels and improved both dyslipidemia and angiogenesis. Combination therapy exhibited less prominent protection compared to individual metals. CONCLUSION: Daily supplementation with trace metals is promising for improving myocardial performance via preventing oxidative damage, induction of angiogenesis, anti-inflammatory and/or anti-hyperlipidemic mechanisms.

Regulatory role of zinc on the biokinetics and biodistribution of (65)Zn during the initiation of experimentally induced colon cancer.

The present study was conducted to evaluate the kinetics of zinc utilization during the formation of colon carcinoma in an animal model of colon carcinogenesis. The rats were segregated into 4 groups: untreated control, 1,2-dimethylhydrazine (DMH) treated, zinc treated, and DMH+zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 wk. Zinc (in the form of zinc sulphate) was supplemented at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of study. Whole body (65)Zn kinetics followed two-compartment kinetics, with Tb(1) representing the initial fast component of the biological half-life and Tb(2), the slower component. The Tb(1) component showed a significant elevation while the Tb(2) component was significantly diminished in DMH-treated rats, which, however, got normalized following zinc supplementation. The biodistribution and subcellular distribution of (65)Zn was significantly affected in DMH-treated rats when compared to normal control rats. However, zinc significantly reversed the altered (65)Zn uptake in different organs and various fractions of colon. The present study for the first time demonstrated a faster mobilization of zinc during initiation of experimentally induced colon carcinoma and provides a physiological basis for the role of zinc in colon tumorigenesis.

Changing the zinc:iron ratio in a cereal-based nutritional supplement has no effect on percent absorption of iron and zinc in Sri Lankan children.

The Thriposha programme is a community-level nutrition intervention in Sri Lanka that provides a combination of energy, protein and micronutrients as a 'ready-to-eat' cereal-based food. We measured the bioavailability of Fe and Zn from Thriposha formula at two different molar ratios of Zn:Fe in order to determine the effect on Fe and Zn absorption. Children 4-7 years (n 53) were given a meal prepared with 50 g Thriposha containing 1.5 mg Zn as zinc sulphate and either 9 mg (high Fe concentration (HiFe)) or 4.5 mg (low Fe concentration (LoFe)) Fe as ferrous fumarate. Zn and Fe percent absorption were measured using stable isotopes by tracer:tracee ratio and by incorporation of erythrocytes, respectively. Percent Fe absorption from the two meals was similar (6.6 % (4.8) v. 4.8 % (2.6); P = 0.15), but total Fe absorption was significantly higher from the HiFe meal (0.59 (0.43) mg) than the LoFe meal (0.20 (0.12) mg; P = 0.01). There was no significant difference between the two groups in Zn absorption (10.7 % (0.9) v. 8.8 % (1.4), P = 0.13, respectively). Decreasing the amount of Fe in Thriposha did not cause a significant change in the percent absorption of Fe and Zn, but significantly lowered the total amount of absorbed Fe. These results demonstrate the utility of maintaining a higher Fe content in this supplement. Further studies to increase Zn content are warranted while maintaining a HiFe.

Inhibitory effect of zinc on hypoxic HIF-1 activation in astrocytes.

Hypoxia-inducible factor-1 (HIF-1) regulates the expression of neuroprotective genes such as erythropoietin (EPO). We investigated the mechanism by which zinc, an excitotoxin-like metal, regulates HIF-1 under hypoxic conditions in astrocytes. In hypoxic LN215 cells, HIF-1alpha stabilized and accumulated in the nucleus, resulting in an increase in its DNA-binding activity to the EPO enhancer. Zinc inhibited hypoxia-induced increases in HIF-1 DNA-binding activity and the HIF-1-dependent mRNA expression of EPO. Zinc did not affect hypoxic stabilization of HIF-1alpha. Nuclear migration of HIF-1alpha upon hypoxia was reduced by zinc. Complete blockade of hypoxia-induced assembly of HIF-1alpha-HIF-1beta complex was observed after treatment of zinc. These findings suggest that zinc hampers hypoxia-stimulated HIF-1 activation in astrocytes by inhibiting nuclear HIF-1alpha translocation and subsequently disrupting HIF-1 heterodimerization.

Uptake of zinc from zinc sulfate and zinc proteinate by ovine ruminal and omasal epithelia.

Uptake and transport of Zn from (65)Zn-labeled ZnSO(4) and Zn proteinate (ZnProt) by ruminal and omasal epithelia were examined by using a parabiotic chamber system. Uptake was measured during a 4-h incubation with 10, 20, or 200 microM Zn as ZnSO(4) or ZnProt in the mucosal buffer (pH 6.0, Krebs-Ringer phosphate). Zinc uptake and transport were also evaluated after simulated ruminal digestion. Buffered ruminal fluid contained a feed substrate and 10 or 200 microM added Zn as ZnSO(4) or ZnProt. In a preliminary experiment, uptake of Zn by omasal tissue was low; thus, the remaining experiments were conducted solely with ruminal epithelium. Incubations to determine the effect of time on Zn uptake from mucosal buffer containing 20 microM added Zn as ZnSO(4) or ZnProt resulted in increased (P < 0.01) Zn uptake as incubation time increased from 30 to 240 min. Zinc uptake was also greater (P = 0.02) from mucosal buffer containing ZnProt compared with ZnSO(4). Zinc uptake from incubations containing 10 or 200 microM was affected by source x concentration (P = 0.05) and concentration x time (P < 0.01) interactions. With 10 microM Zn, uptake was not influenced by Zn source, whereas when 200 microM Zn was added, Zn uptake from ZnProt was greater than from ZnSO(4). Increasing incubation time resulted in increased Zn uptake with 200 microM Zn in the mucosal buffer; however, with 10 microM Zn, uptake did not change after 30 min. After simulated ruminal fermentation, the proportion of Zn in a soluble form was influenced by a source x concentration interaction (P = 0.03). After 18 h of incubation, the proportion of Zn that was soluble was not different between ZnProt and ZnSO(4) in buffered ruminal fluid that contained 10 microM added Zn, but was greater for ZnProt compared with ZnSO(4) with 200 microM Zn in the incubation. Zinc uptake from the aqueous fractions of simulated ruminal digestions containing 200 microM added Zn was greater (P < 0.01) than from those containing 10 microM added Zn. Zinc transport, based on detection of (65)Zn in serosal buffer, did not occur in any of the experiments. The results of the current experiments suggest that absorption of Zn into the bloodstream does not occur from the ruminant foresto-mach; however, Zn uptake occurs in ruminal tissue and is greater from ZnProt than from ZnSO(4).

Zinc sulphate following the administration of iodine-131 on the regulation of thyroid function, in rats.

Hyperthyroidism in men is often treated with high doses of iodine-131 ((131)I), which may induce radiation side effects to patients and their environment. These therapeutic doses of (131)I could be decreased, if the (131)I uptake of the thyroid gland of the patients could be increased. Zinc sulphate has been considered to exercise a protective role by maintaining the cellular integrity of the thyroid under various pathological states. The aim of our study was to study in Wistar rats whether zinc sulphate can after treatment of the thyroid gland with (131)I: a) increase the uptake of (131)I in the thyroid and b) stabilize the function of the follicular cells. If such a stabilization finally exists in men we could have favorable results like fewer cases of hypothyroidism after (131)I treatment of hyperthyroidism. To carry out these investigations, rats were divided into four groups comprising of eight animals each. Group I animals served as normal controls. Group II animals received a dose of 3.7 MBq of (131)I. Group III animals were supplemented with zinc (227 mg/L of drinking water) and animals in Group IV were given (131)I together with zinc sulphate as above. Our results showed that in Group II, serum levels of tetra-iodo-thyronine (T(4)) and tri-iodo-thyronine (T(3)) decreased significantly as a function of time following (131)I treatment. An increase in the levels of serum thyroid stimulating hormone (TSH) was noticed one week after (131)I treatment, becoming less pronounced with time. In Group II, thyroid uptake at 2h and at 24h was significantly decreased. In the same Group biological half life (T(biol)) of (131)I in the thyroid gland, was significantly elevated four weeks after the administration of (131)I and decreased eight weeks after. In Group IV animals, zinc sulfate after four weeks, induced normalization of elevated serum TSH levels and a further increase in the T(biol) of (131)I. After eight weeks in these animals, serum T(3) became normal and TSH remained at normal levels. Thyroid (131)I uptake at 2 and 24 h was increased as compared to Group II. Group III animals showed some increase in the levels of Na(+)K(+)ATPase and type 1,5'-deiodinase (5'-DI) as compared to normal rats of Group I. In conclusion, this study suggests the protective potential of zinc sulphate in the disturbed after (131)I treatment, thyroid function, thyroid hormones and TSH while the (131)I uptake was reduced. Thus, if this result is further confirmed, zinc sulphate may show to be a promising radioprotective agent for the thyroid gland.

Chemopreventive potential of zinc in experimentally induced colon carcinogenesis.

The present study was performed to evaluate the efficacy of zinc treatment on colonic antioxidant defense system and histoarchitecture in 1,2-dimethylhydrazine- (DMH) induced colon carcinogenesis in male Sprague-Dawley rats. The rats were segregated into four groups viz., normal control, DMH treated, zinc treated, DMH+zinc treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of the study. Increased tumor incidence, tumor size and number of aberrant crypt foci (ACF) were accompanied by a decrease in lipid peroxidation, glutathione-S-transferase, superoxide dismutase (SOD) and catalase. On the contrary, significantly increased levels of reduced glutathione (GSH) and glutathione reductase (GR) were observed in DMH treated rats. Administration of zinc to DMH treated rats significantly decreased the tumor incidence, tumor size and aberrant crypt foci number with simultaneous enhancement of lipid peroxidation, SOD, catalase and glutathione-S-transferase. Further, the levels of GSH and GR were also decreased following zinc supplementation to DMH treated rats. Well-differentiated signs of dysplasia were evident in colonic tissue sections by DMH administration alone. However, zinc treatment to DMH treated rats greatly restored normalcy in the colonic histoarchitecture, with no apparent signs of neoplasia. EDXRF studies revealed a significant decrease in tissue concentrations of zinc in the colon following DMH treatment, which upon zinc supplementation were recovered to near normal levels. In conclusion, the results of this study suggest that zinc has a positive beneficial effect against chemically induced colonic preneoplastic progression in rats induced by DMH.