Sialoadenectomy enhances hepatic injury induced by lipopolysaccharide/galactosamine in mice.
BACKGROUND
Submandibular salivary glands (SMGs) synthesize, accumulate and secrete a large amount of epidermal growth factor (EGF) in mice. It is known that surgical removal of SMG (sialoadenectomy) alters cell turnover in the liver and exacerbates liver injury induced by lipopolysaccharide/galactosamine (LPS/GalN).


RESULTS
Here we show that such increased hepatotoxicity is not the consequence of the lack of EGF production from SMG. On the contrary, it appears to be the consequence of an inadequate cytokine production by the liver of sialoadenectomized mice. Thus, we found that the increase of plasma tumour necrosis factor-alpha and interleukin-6 was slower in sialoadenectomized than in sham-operated mice. This is because of a decreased rate of production of both cytokines by the liver. We found that the increase of plasma corticosterone (CS) concentration is lower in sialoadenectomized than that in sham-operated mice. Adrenalectomy exacerbated liver injury induced by LPS/GalN. In these animals, sialoadenectomy did not further increase the effect of LPS/GalN.


CONCLUSIONS
Our results suggest that the effect of sialoadenectomy on LPS/GalN-induced liver toxicity may be the consequence of an altered cytokine production by the liver and a reduced CS release from adrenal glands.
Sánchez
Olga
O
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Almagro
Albert
A
Viladrich
Meritxell
M
Ramírez
Ignasi
I
Soley
Maria
M
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005688:Galactosamine / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D010477:Perfusion; D009195:Peroxidase / Q000378:metabolism; D013363:Submandibular Gland / Q000601:surgery*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003345:Corticosterone