Nicotinic Acid Coated Magnetite Nanorods Evaluation by Lipid Profile Analysis and Genetic Tests.

In our present work some biological tests were carried out to assess the biocompatibility of nicotinic acid coated magnetite nanorods. Pure and coated nanorods were injected intraperitoneally to cholesterol fed mice with dose values of 25, 50 mg/Kg. Investigations were done on treated mice with/without exposure to low frequency electromagnetic field (EMF) and samples were collected fourteen days post treatment. Toxicological effects were evaluated using Micronucleus and DNA fragmentation analysis. The results indicated that low dose (25 mg/Kg) nicotinic acid coated nanorods had insignificant toxicological effects in comparison to that of control group. Lipid profile analysis and gene expression of atheroprotective (eNOS) and atherogenic (p65) genes were also investigated. It was found that experimental groups treated with low dose nicotinic acid coated magnetite nanorods and exposed to EMF showed interesting alterations in mice lipid profile. As a result, an insignificant but slight increase in gene expression levels of eNOS and a significant decrease in p65 gene expression were observed. Our study suggests that our proposed magnetic nanosystem in combination with EMF has good biocompatibility and can be a potential drug precursor with therapeutic values.

Influences of incorporating detoxified Jatropha curcas kernel meal in common carp (Cyprinus carpio L.) diet on the expression of growth hormone- and insulin-like growth factor-1-encoding genes.

Jatropha curcas is a drought-resistant shrub or small tree widespread all over the tropics and subtropics. The use of J. curcas (L) kernel meal in fish feed is limited owing to the presence of toxic and antinutritional constituents. In this study, it was detoxified using heat treatment and organic solvent extraction method. The detoxification process was carried out for 60 min to obtain the detoxified meal. Cyprinus carpio L. fingerlings (n = 180; avg. wt. 3.2 ± 0.07 g) were randomly distributed in five treatment groups with four replicates and fed isonitrogenous diets (crude protein 38%) for 8 weeks. The inclusion levels of the detoxified Jatropha kernel meal (DJKM) and soybean meal (SBM) were as follows: control diet was prepared with fish meal (FM) and wheat meal, without any DJKM and SBM; diets S(50) and J(50) : 50% of FM protein replaced by SBM and DJKM respectively; diets S(75) and J(75) : 75% of FM protein replaced by SBM and DJKM respectively. Highest body mass gain and insulin-like growth factor-1 (IGF-1) gene expression in brain, liver and muscle were observed for the control group, which were statistically similar to those for J(50) group and significantly (p < 0.05) higher than for all other groups, whereas growth hormone gene expression in brain, liver and muscle exhibited opposite trend. Insulin-like growth factor-1 concentration in plasma did not differ significantly among the five groups. Conclusively, growth performance was in parallel with IGF-1 gene expression and exhibited negative trend with GH gene expression.

Effect of food restriction on reproductive-related genes and reproductive hormones in adult female rats.

OBJECTIVES: A number of factors involved in the control of energy balance and metabolism act as modulators of gonadal axis. Ghrelin, a peptide secreted from the stomach and hypothalamus, has emerged as an orexigenic food intake controlling signal acting upon hypothalamus. Recently, the potential reproductive role of ghrelin has received great attention. This study was designed to investigate the influence of food restriction and consequent metabolic hormone (ghrelin) on the level and gene expression of female reproductive hormones in adult rats. MATERIALS AND METHODS: To study the effect of chronic food restriction on ghrelin level in adult female rats and its relation to female reproductive hormones, 32 adult female Sprague Dawley rats divided into 4 groups: Group I (control group) comprised 8 rats fed ad libitum for 30 days, Group II, III and IV (food-restricted groups for 10, 20 and 30 days respectively) each consisted of 8 rats fed 50% of ad libitum intake determined by the amount of food consumed by the control group. RESULTS: Mean body weight of food restricted rats was observed to decrease during the period of the experiment. Food restriction produced significant increase of serum ghrelin with significant decrease of both gastric and hypothalamic ghrelin accompanied with significant increase in its gene expression in stomach and hypothalamus. Estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed significant decrease correlated with down-regulation of gonadotropins, cyclin-dependent kinase (cdc2), cyclin B and kisspeptin (Kiss1) genes in food restricted rats compared with control group. CONCLUSIONS: Ghrelin could be one of the hormones responsible for the suppression of female reproductive axis in case of negative energy balance. Thus, ghrelin may operate as an autocrine/paracrine regulator of ovarian function. Overall, ghrelin may represent an additional link between body weight homeostasis and reproductive function.

Nanotoxicity of gold and gold-cobalt nanoalloy.

Nanotoxicology test of gold nanoparticles (Au NPs) and gold-cobalt (Au-Co) nanoalloy is an important step in their safety evaluation for biomedical applications. The Au and Au-Co NPs were prepared by reducing the metal ions using sodium borohydride (NaBH(4)) in the presence of polyvinyl pyrrolidone (PVP) as a capping material. The average size and shape of the nanoparticles (NPs) were characterized using high resolution transmission electron microscopy (HRTEM). Cobalt presence in the nanoalloy was confirmed by energy dispersive X-ray spectroscopy (EDX) analysis, and the magnetic properties of these particles were determined using a vibrating sample magnetometer (VSM). The Gold and gold-cobalt NPs of average size 15 ± 1.5 nm were administered orally to mice with a dose of 80, 160, and 320 mg/kg per body weight (bw) using gavages. Samples were collected after 7 and 14 days of the treatment. The results indicated that the Au-Co NPs were able to induce significant alteration in the tumor-initiating genes associated with an increase of micronuclei (MNs) formation and generation of DNA adduct (8-hydroxy-2-deoxyguanosine, 8-OHdG) as well as a reduction in the glutathione peroxidase activity. This action of Au-Co NPs was observed using 160 and 320 mg/kg bw at both time intervals. However, Au NPs had much lower effects than Au-Co NPs on alteration in the tumor-initiating genes, frequency of MNs, and generation of 8-OHdG as well as glutathione peroxidase activity except with the highest dose of Au NPs. This study suggests that the potential to cause in vivo genetic and antioxidant enzyme alterations due to the treatment by Au-Co nanoalloy may be attributed to the increase in oxidative stress in mice.

Genotoxicity evaluation of nanomaterials: dna damage, micronuclei, and 8-hydroxy-2-deoxyguanosine induced by magnetic doped CdSe quantum dots in male mice.

Quantum dots (QDs) are a novel class of inorganic fluorophores which are gaining widespread recognition as a result of their exceptional photophysical properties and their applications as a biomarker and in molecular biomedical imaging. The aim of this study was to evaluate the in vivo genotoxicity in mice exposed to CdSe quantum dots of average size 5.0 ± 0.2 nm and CdSe doped with 1% cobalt ions of similar size. The quantum dots are surface modified using mercaptoacetic acid (MAA) in order to be biocompatible and water-soluble. The MAA-QDs were given to the mice orally at doses of 500, 1000, and 2000 mg/kg by weight of MAA-QDs. Bone marrow and liver samples were collected after two and seven days of treatment. The results indicated that after two days of treatment, the high dose of doped MAA-QDs was significantly able to induce DNA damage, formation of micronuclei (MNs), and generation of DNA adduct (8-hydroxy-2-deoxyguanosine, 8-OHdG). However, increasing DNA damage and the frequency of MNs formation as well as the generation of DNA adducts were observed with both the undoped MAA-QDs (2000 mg/kg) and doped MAA-QDs (1000 and 2000 mg/kg) after seven days of treatment. The results of our study indicate that exposure to high doses of pure MAA-QDs or MAA-QDs doped with cobalt has the potential to cause indirect in vivo genetic damage, which may be attributed to free radical-induced oxidative stress in mice.

Molecular forms of alpha-melanocyte-stimulating hormone in pheochromocytoma tissue.

The molecular forms of alpha-melanocyte-stimulating hormone (MSH) in pheochromocytoma tissues have been characterized using reversed-phase HPLC and radioimmunoassay. Six alpha-MSH-related peptides were detected. Three of the six peaks had elution times identical to those of synthetic desacetyl-alpha-MSH, alpha-MSH and diacetyl-alpha-MSH. The remaining three forms of the alpha-MSH-like immunoreactivity suggest a different processing of pro-opiomelanocortin in this tissue than in the intermediate lobe of the pituitary gland. Current results confirm that alpha-MSH are present in human pheochromocytoma and suggest that alpha-MSH has role in the pathophysiology of this tissue.

Functional membrane changes due to tumor induction in rat pituitary cell cultures.

Membrane functions in tumorous cells are different from those in healthy cells. The aim of the present study was to investigate the changes in pituitary cell membrane functions and hormone secretion after tumor induction in vivo and in vitro. Prolactinomas were induced in vivo in female Wistar rats with estrone acetate. Normal anterior pituitaries and prolactinomas of female Wistar rats were dissociated enzymatically and mechanically, then cultured on collagen-treated plastic dishes. Some normal anterior pituitary cultures were treated with benz(c)acridines as tumorigenic agents in vitro. Intracellular 3',5'-cyclic-adenosine monophosphate (cAMP) levels were determined by a competitive binding technique, membrane fluidity was assayed by fluorescence anisotropy, and ATP-ase activities were estimated via ATP loss. The results indicated decreased membrane fluidity in tumorous cell cultures. However, in vitro benz(c)acridine treatment exerted more pronounced effects than those observed after in vivo estrone treatment. The ATP-ase activities were highly increased in benz(c)acridine-treated cells and in estrogen-induced prolactinoma cells, more strongly so in the former ones. The intracellular cAMP levels were higher than normal in both of them. The results concerning the ACTH, alpha-MSH, PRL and GH levels of normal and tumorous cell cultures were published in our previous study. Our findings show that the tumorous transformation of pituitary cells can cause significant changes in functional membrane parameters and hormone secretion. Decreased membrane fluidity was accompanied by an increased exocytosis (hormone release) and adenylate cyclase activity in tumorous cells.

Surface changes and hormone production in pituitary cells during tumorigenesis.

Prolactinomas were induced by chronic estrone acetate treatment in female Wistar rats in vivo. After enzymatic dissociation of the tumor tissue, monolayer cell cultures were obtained. In vitro tumor induction was performed by treatment of normal monolayer anterior pituitary cell cultures with a 1:1 mixture of 7,9-dimethylbenz[c]acridine: 8-methylbenz[c]acridine. For immunohistochemistry, the cell cultures were stained by the peroxidase-antiperoxidase method for standardization; the nonspecific hormone release was induced with 30 mM K+. The prolactin, alpha-melanotropin, and adrenocorticotropin levels in the supernatant were measured by specific, sensitive radioimmunoassays. The results indicated surface differences between the in vivo induced prolactinoma cells and normal pituitary cells: the attachment of the prolactinoma cells required 15% collagen treatment, whereas normal cells required only 3-4% collagen. Tumor cells induced in vitro by methylbenz[c]acridine treatment were able to attach only after ammonia activation of the collagen surface. These findings strongly suggest that the mode of tumor induction can result in differences in membrane fluidity; this phenomenon is possibly connected with the levels of prolactin, adrenocorticotropin and alpha-melanotropin hormone production of these endocrine tumor cells.