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PubMed1985

Combined toxic effects of tetracycline and ethinyl estradiol on liver function of mice.

The combined effects of ethinyl estradiol (EE) (0.5 micrograms/g s.c. once daily for 4 days) and tetracycline (TC) or doxycycline (DC) (50 micrograms/g i.v.) on liver weight and water content, serum transaminases, alkaline phosphatase, urea, triglycerides, and cholesterol as parameters of various liver functions were investigated in mice. It became apparent that depending on the parameter tested synergistic and antagonistic effects may occur, e.g., synergistic effects were observed with the serum transaminases and liver cholesterol; antagonistic effects were seen with the serum urea and serum cholesterol.

Alanine Transaminase↗
PubMed1997

Gluconeogenesis in patients with impaired liver function.

This presentation gives an overview about the factors involved in the regulation of gluconeogenesis. Then, based on these regulatory principles, the changes seen in impaired liver function are discussed. Gluconeogenesis from lactate and pyruvate is mediated through pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK) activity. The PC mediated pathway depends on substrate supply and on the downregulation of the oxidative pathway for pyruvate. Both enzymes need ATP or GTP and, thus, depend on the cellular energy charge. Tissue anoxia can reduce the energy charge and limit the flow through the PEPCK pathway. Thus, one expects a coupling between reduced splanchnic blood flow, limited oxygen supply to the liver, resulting tissue anoxia, and reduced gluconeogenesis. Conditions are shown, where this coupling exists. Since gluconeogenesis is concentrated in the periportal region of the liver, the local oxygen tension is sufficient under many circumstances to maintain a high glucose production level. Also, the enzyme activity of PEPCK can compensate for long term anoxia. Thus, gluconeogenesis is sufficient in most cases, as seen in critically ill patients. However, this could be associated with a reduction in the perivenous oxygen tension, possibly below critical levels. Beta-adrenergic stimulation increases gluconeogenesis. Examples are shown where this stimulation can overlay the dependency on the oxygen tension and substrate supply. Catecholamines are generally used to stabilize the hemodynamic system. This treatment could limit splanchnic bloodflow and, as a consequence, the oxygen supply to the liver with a simultaneous stimulation of gluconeogenesis and can cause severe anoxia in the perivenous region. These negative side effects of catecholamine treatment should be avoided and the ideal treatment should aim at improving splanchnic flow without stimulation of gluconeogenesis.

Gluconeogenesis↗
PubMed1998

Liver function in cirrhotic patients in the euthyroid versus the hypothyroid state.

We recently showed that some decrease in thyroid hormone blood levels can effectively and significantly prevent the development of cirrhosis and fulminant hepatic failure and decrease portal pressure in three different rat models. This study was conducted to determine whether hypothyroidism has a beneficial effect over euthyroidism on patients with active liver cirrhosis of different etiologies. The medical files of hypothyroid patients with cirrhosis who were referred to the Tel-Aviv Medical Center between the years 1980 and 1995 were retrospectively evaluated. Of 3,528 patients with biopsy-proven cirrhosis and 4,738 hypothyroid patients who were identified, only 46 (25 female, 54%; mean age, 52.3 +/- 9.1) met the eligibility criteria. The patients suffered from cirrhosis (mean, 9.5 +/- 4.3 years; range, 4-23) and had hypothyroidism (mean, 12 +/- 6 years; range, 4-31). Most patients suffered from hypothyroidism of unknown etiology (85%), whereas the rest had hypothyroidism after surgical/iodine ablation of the gland. In the hypothyroid versus the euthyroid state, a significant negative correlation was found between thyroid-stimulating hormone blood levels and both functional and synthetic liver function tests (p < 0.001). A significant negative correlation was also found between thyroid-stimulating hormone blood levels and clinical deterioration manifested as bleeding varices, the development of ascites, and episodes of encephalopathy. We conclude that in patients with liver cirrhosis, the liver function in the hypothyroid state tend to be better than in the euthyroid state. A mild controlled decreased thyroid function may be beneficial for euthyroid cirrhotic patients.

Acute Disease↗