Purpose Hyponatremia is the most frequent electrolytic disorder in clinical practice. In addition to neurological symptoms, hyponatremia, even when mild/moderate and chronic, has been related to other manifestations, such as bone demineralization and increased risk of fractures. To better elucidate tissue alterations associated with reduced serum sodium concentration [Na+], we developed an in vivo model of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. Methods and results Hyponatremia was induced in Foxn1(nu/nu) mice by subcutaneous infusion of the vasopressin analog 1-deamino [8-D-arginine] vasopressin (dDAVP) for 14 days via osmotic mini-pumps. Mice in the control group were infused with isotonic saline solution. Serum [Na+] progressively decreased, with a nadir of 123.4 +/- 2.3 mEq/L (mean +/- SD, dDAVP 0.3 ng/h) and 111.6 +/- 4.7 mEq/L (mean +/- SD, dDAVP 0.5 ng/h). Evident signs of liver steatofibrosis were observed at histology in hyponatremic mice. Accordingly, the expression of proteins involved in lipid metabolism (SREBP-1, PPAR alpha and PPAR gamma) and in myofibroblast formation (alpha SMA and CTGF) significantly increased. Furthermore, heme oxygenase 1 expression was up-regulated in Kupffer and hepatic stellate cells in the liver of hyponatremic mice. Testis alterations were also observed. In particular, the thickness of the seminiferous epithelium appeared reduced. The expression levels of PCNA and PTMA, which are involved in DNA replication and germ cells maturation, were markedly reduced in the testis of hyponatremic mice. Conclusion Overall, these findings shed new light on the possible consequences of chronic hyponatremia and prompt a more thorough evaluation of hyponatremic patients.

Hyponatremia-related liver steatofibrosis and impaired spermatogenesis: evidence from a mouse model of the syndrome of inappropriate antidiuresis / Marroncini, G; Anceschi, C; Naldi, L; Fibbi, B; Brogi, M; Lanzilao, L; Fanelli, A; Maggi, M; Peri, A. - In: JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION. - ISSN 0391-4097. - STAMPA. - 46:(2023), pp. 967-983. [10.1007/s40618-022-01962-9]

Hyponatremia-related liver steatofibrosis and impaired spermatogenesis: evidence from a mouse model of the syndrome of inappropriate antidiuresis

Marroncini, G;Anceschi, C;Naldi, L;Fibbi, B;Brogi, M;Lanzilao, L;Fanelli, A;Maggi, M;Peri, A
2023

Abstract

Purpose Hyponatremia is the most frequent electrolytic disorder in clinical practice. In addition to neurological symptoms, hyponatremia, even when mild/moderate and chronic, has been related to other manifestations, such as bone demineralization and increased risk of fractures. To better elucidate tissue alterations associated with reduced serum sodium concentration [Na+], we developed an in vivo model of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. Methods and results Hyponatremia was induced in Foxn1(nu/nu) mice by subcutaneous infusion of the vasopressin analog 1-deamino [8-D-arginine] vasopressin (dDAVP) for 14 days via osmotic mini-pumps. Mice in the control group were infused with isotonic saline solution. Serum [Na+] progressively decreased, with a nadir of 123.4 +/- 2.3 mEq/L (mean +/- SD, dDAVP 0.3 ng/h) and 111.6 +/- 4.7 mEq/L (mean +/- SD, dDAVP 0.5 ng/h). Evident signs of liver steatofibrosis were observed at histology in hyponatremic mice. Accordingly, the expression of proteins involved in lipid metabolism (SREBP-1, PPAR alpha and PPAR gamma) and in myofibroblast formation (alpha SMA and CTGF) significantly increased. Furthermore, heme oxygenase 1 expression was up-regulated in Kupffer and hepatic stellate cells in the liver of hyponatremic mice. Testis alterations were also observed. In particular, the thickness of the seminiferous epithelium appeared reduced. The expression levels of PCNA and PTMA, which are involved in DNA replication and germ cells maturation, were markedly reduced in the testis of hyponatremic mice. Conclusion Overall, these findings shed new light on the possible consequences of chronic hyponatremia and prompt a more thorough evaluation of hyponatremic patients.
2023
46
967
983
Marroncini, G; Anceschi, C; Naldi, L; Fibbi, B; Brogi, M; Lanzilao, L; Fanelli, A; Maggi, M; Peri, A
File in questo prodotto:
File Dimensione Formato  
Marroncini et al., 2023.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 3.25 MB
Formato Adobe PDF
3.25 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1308575
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 1
social impact