The immuno-reconstituting effectof melatonin or pineal grafting and its relation to zinc pool in aging mice

Mocchegiani, Eugenio; Bulian, Daniele; Santarelli, Lory; Tibaldi, Alberto; Muzzioli, Mario; Pierpaoli, Walter; Fabris, Ν.

doi:10.1016/0165-5728(94)90029-9

Cited by 75 publications

(58 citation statements)

References 48 publications

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“…The evidence that the downregulation of HER-2/neu expression induces apoptosis in HER-2/neuoverexpressing cells supports the antitumoral effect of epitalon mediated by a HER2/neu modulation. 26 Whether melatonin may directly act on tumor cells inhibiting HER-2/neu expression or its effect is indirectly due to the in vivo modulation of other factors 25,27 remains to be demonstrated. The fact that the thymic dipeptide Vilon, which failed to positively influence the mammary carcinogenesis in the transgenic HER-2/neu mice, also partially reduced HER2/neu mRNA expression may imply that the HER2/neu downregulation does not represent the only mechanism involved in the antitumoral action of Epitalon.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

Anisimov

Khavinson

Provinciali

et al. 2002

Intl Journal of Cancer

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Female FVB/N HER-2/neu transgenic mice from the age of 2 months were subcutaneously injected with saline, the peptide Epitalonா (Ala-Glu-Asp-Gly) or with the peptide Vilonா (Lys-Glu) in a single dose of 1 g/mouse for 5 consecutive days every month. Epitalon treatment reduced the cumulative number and the maximum size of tumors (p < 0.05). Furthermore, the number of mice bearing 1 mammary tumor was increased, whereas the number of mice bearing 2 or more mammary tumors was reduced in Epitalon-treated in comparison to saline-treated animals (p < 0.05). The size but not the number of lung metastases was reduced in Epitalontreated compared to saline-treated mice (p < 0.05). The treatment with Vilon produced significant negative effects when compared to the control group, with an increased incidence of mammary cancer development (p < 0.05), a shorter mean latent period of tumors (p < 0.05) and an increased cumulative number of tumors (p < 0.05). A 3.7-fold reduction in the expression of HER-2/neu mRNA was found in mammary tumors from HER-2/neu transgenic mice treated with Epitalon compared to control animals. The expression of mRNA for HER-2/neu was also partially reduced in Vilon-treated mice, but it remained significantly higher in Vilon-than in Epitalon-treated animals (1.9-fold increase). The data demonstrate the inhibitory effect of Epitalon in the development of spontaneous mammary tumors in HER-2/ neu mice, suggesting that a downregulation of HER-2/neu gene expression in mammary adenocarcinoma may be responsible, at least in part, for the antitumor effect of the peptide. © 2002 Wiley-Liss, Inc. Key words: peptide; HER-2/neu; transgenic mice; mammary cancerBreast cancer is one of the most common cancers and is a leading cause of mortality in women. 1,2 The HER-2/neu oncogene encodes a 185 kDa (p 185) receptor protein belonging to the epidermal growth factor receptor family involved in organogenesis and epithelial differentiation. 3 Amplification and mutation of HER-2/neu plays a pathogenetic role in several malignancies, including carcinoma of the breast, ovary and uterus. 4,5 Overexpression of ErbB-2/HER-2/neu occurs in 15-40% of human breast cancers. 6 Its appearance correlates with poor prognosis, and it is, therefore, an important target for physiologic investigation and therapeutic intervention. 5 It has been shown that treatment with the pineal indole hormone melatonin inhibits the development of mammary gland tumorigenesis both in vitro and in vivo. [7][8][9][10] It was also shown that the polypeptide pineal preparation Epithalamin inhibits both the growth of transplantable mammary tumors and the development of spontaneous mammary tumors in female C3H/Sn and SHR mice and mammary carcinogenesis induced by 7,12-dimethylbenzanthracene mammary tumors or by total-body X-ray irradiation in female rats. 11-13 Clinical use of Epithalamin was shown to be effective for the treatment of ovarian disturbances and of some types of cancer, breast cancer included. 14 However, the in vivo use of Epithalamin has been rathe...

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Section: Discussionmentioning

confidence: 99%

Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

Anisimov

Khavinson

Provinciali

et al. 2002

Intl Journal of Cancer

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“…Tissue Zn levels have been found altered after pinealectomy in rats [6,16]. MEL treatment and pineal grafting has been induced a restoration of the altered Zn turnover in old age as revealed by the shift of Zn crude balance from negative to positive values, approaching those of young mice [12].…”

Section: Discussionmentioning

confidence: 99%

“…MEL treatment or pineal graft induced a restoration of the alterated Zn turnover in old mice. It has been suggested that MEL can play a role Zn turnover and the effect of MEL on thymic endocrine activity and peripheral immune functions may be mediated by Zn [12]. The aim of this study was to determine the effect of MEL treatment on tissue Zn levels in young and middle-aged rats.…”

Section: Introductionmentioning

confidence: 99%

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Effect of melatonin treatment on liver and thymus zinc levels in young and middle‐aged rats

Öztürk

Akbulut

Afrasyap

et al. 2004

J Trace Elements Exper Med

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Melatonin (MEL) is the main neurohormone of the pineal gland. Zinc (Zn) is an essential trace element that is required as a catalytic component for more than 200 enzymes. Both MEL and Zn are considered beneficial for anti-immunosenescence. Recent findings have shown that MEL can modulate Zn turnover. The aim of this study was to investigate the effect of MEL treatment on the tissue Zn levels in young (4 months) and middle-aged (14 months) rats. Male wistar rats received during 3 weeks subcutaneous injection of MEL (10 mg/kg). After 3 weeks, rats were decapitated and tissue samples were collected. Zn levels were measured by spectrophotometric assay. In conclusion, MEL decreased liver Zn levels both in young and middle-aged rats. In addition, Zn levels in young control group were significantly higher than middle-aged control group. However, MEL treatment increased thymus Zn levels in middle-aged group compared with the control. These findings indicate that tissue Zn levels are significantly affected by MEL treatment.

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“…Melatonin, the main neurohormone synthesised and secreted by the pineal gland, has been suggested to increase the absorption of zinc within the digestive system. In the presence of specific binding sites for melatonin in the intestine, it is seen as an essential mechanism for increasing the absorption of zinc in the digestive tract (Mocchegiani et al, 1994). In our study, the presences of; i) a marked increase (P<0.001) of Zn in the MEL group on Day zero as compared to Day -35, ii) a further increase (P<0.001) in the MELNOR group on Day -10 as compared to the Day -35, and iii) its continuation during the oestrus are all in line with the literature (Mocchegiani et al, 1994;1996).…”

Section: Minerals Valuesmentioning

confidence: 99%

Is there a relationship between serum minerals (Ca, Mg) and trace elements (Cu, Fe, Mn, Zn) at mating on pregnancy rates in fat-tailed Morkaraman sheep?

Uslu

Mıs

Gülyüz

et al. 2017

IJAR

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The specific roles of nutrients in reproduction are not well defined in sheep. Hence, the relationships between certain mineral (Ca, Mg) and element (Cu, Fe, Mn, Zn) levels at mating and pregnancy rates was investigated in fat-tailed Morkaraman ewes synchronised with different hormones (melatonin, norgestomet implant and eCG) early in anoestrus season. For this purpose, 40 healthy ewes (aged 2-4 years) allocated in the synchronised (n=30) and no-treated group (n=10) were used during mid-May (suckling period). On the eCG injection day, fertile rams (n=8) were introduced into the groups and, then the oestrus signs were visually monitored twice daily for 7 days. The oestrous ewes were allowed to handmate using rotational (four rams daily) mating system. Additionally, jugular blood samples were collected on the days of onset of oestrus (before mating) for determination of serum Ca, Cu, Fe, Mg, Mn and Zn levels. Presence of pregnancies was diagnosed by real-time ultrasonography 35 days post-mating. Totally, 25 ewes became pregnant (21 ewes with stimulatedand 4 with spontaneous oestrus), while 9 ewes (all received stimulation) were not pregnant. In non-pregnant ewes, unlike other minerals and elements, the Cu and Zn values were significantly lower than their reference values (for Cu: 0.87±0.16 mg/dl vs. 9.20 mg/dl; for Zn: 2.06±0.30 g/dl vs. 3.8 g/dl, resp.; P<0.01 in both cases). In pregnant ewes, the corresponding values remained unchanged (P>0.05). Hence, the present findings indicate that the low Cu and Zn levels during the oestrus might adversely affect the subsequent pregnancy rate in suckling ewes.

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The immuno-reconstituting effectof melatonin or pineal grafting and its relation to zinc pool in aging mice

Cited by 75 publications

References 48 publications

Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

Effect of melatonin treatment on liver and thymus zinc levels in young and middle‐aged rats

Is there a relationship between serum minerals (Ca, Mg) and trace elements (Cu, Fe, Mn, Zn) at mating on pregnancy rates in fat-tailed Morkaraman sheep?

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