Sialoadenectomy alters liver cell turn‐over and function in mice

Abstract

In rodents, submandibular salivary glands accumulate a number of biologically active peptides, and release some of them to both saliva and the bloodstream. Surgical removal of these glands (sialoadenectomy) alters the ability of the liver to regenerate after partial hepatectomy. We show here that 5 weeks after surgery, the liver of sialoadenectomized mice contained 40% fewer hepatocytes than the liver of sham-operated mice. We did not obtain evidence of necrotic cell death after surgery. In contrast, sialoadenectomy transiently increased apoptotic hepatocyte death, as revealed by terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling (TUNEL) assay. DNA synthesis was determined in vivo by the incorporation of bromo-deoxyuridine (BrdU) into hepatocyte nuclei. BrdU-labeling progressively increased after sialoadenectomy. We conclude that sialoadenectomy induced a transient wave of apoptotic cell death followed by a rise in DNA synthesis but not by cell division. This reduced cell number but increased mean cell volume. In spite of these alterations in cellularity, the liver responded adequately to several stressful conditions, as judged by the lack of any differential effect of sialoadenectomy on liver glycogen and plasma glucose concentration after immobilization, aggressive encounter, or fasting. However, the liver of sialoadenectomized mice was more sensitive to the effect of a non-lethal dose of bacterial lipopolysaccharide (LPS) combined with d-galactosamine, as shown by the enhanced rise in plasma alanine aminotransferase and aspartate aminotransferase, and liver myeloperoxidase (MPO) activities. All these results indicate that a submandibular salivary glands-liver axis is involved in the maintenance of liver structure in mice. A disturbance of this axis induces an adaptive response that preserves the metabolic function of the liver but renders it more sensitive to bacterial endotoxins.

Liver injury after an aggressive encounter in male mice

“…In agreement, we have observed a transient increase in hepatocyte apoptosis coincident with a transient disappearance of EGF shortly after sialoadenectomy (13). This suggests that EGF may protect the liver against some insults but not against others.…”

Endogenous EGF maintains Sertoli germ cell anchoring junction integrity and is required for early recovery from acute testicular ischemia/reperfusion injury

“…1B). This is as expected because EGF is expressed in many other cells and tissues and, in some of them, EGF expression is upregulated upon sialoadenectomy (Buira et al 2004). These results collectively prompted us to choose postoperative 1 week as the time-point for the subsequent study.…”

“…They were allowed to acclimatize for at least 1 week before the experiment. Sialoadenectomy was carried out in mice as described previously (Buira et al 2004). Briefly, a small incision was made to expose the submandibular salivary glands and the tissues were then ligated and excised.…”

Glucose Directly Links to Lipid Metabolism through High Affinity Interaction with Peroxisome Proliferator-activated Receptor α

“…Protein bands were quantified by densitometry, utilizing a single-chip charge-coupled device video camera FluorChemimager and accompanying FluorChem image analysis software from Alpha Innotech (San Leandro, CA). Total cell number, intracellular volume, and nuclear volume were 1.7 ϫ 10 8 cells/g of liver, 6.2pL, and 1.8pL, respectively, as determined previously (26,27). Final concentrations were calculated from the amount of PPAR␣ protein in the whole cell or nucleus divided by the estimated respective volumes of the whole cell and nucleus.…”