[Liver changes in protein malnutrition. An experimental study in rats]. / Cambios hepáticos en la malnutrición proteica. Estudio experimental en ratas.

It is known that protein malnutrition conditions the development of liver steatosis, and may be accompanied by fibrosis. Ito cells intervene in the fibrogenesis, converting to transitional cells and myofibroblasts. Some trace elements, such as copper (Cu), iron (Fe) and manganese (Mn) act as co-factors, and zinc (Zn) acts as an inhibitor of a variety of enzymes involved in the collagen synthesis. This study analyzes the effects on the livers of 12 mate Wistar rats following two months administration of a hypoproteic (6%) isocaloric diet, comparing histomorphometric parameters (hepatocyte and nucleum area, total fat and fibrosis) and the liver content in Fe, Cu, Zn and Mn, with those in 12 control rats of similar age and sex. The experimental group revealed a significant reduction in hepatocyte nucleum area (p < 0.001), an increase in the ratio of hepatocyte cytoplasmatic and nucleum hepatocyte area, pronounced steatosis and slight fibrosis. No differences were found in Ito cell percentages. The experimental group showed a significant increase in liver content of Fe (p = 0.01) and a significant drop in Mn content (p < 0.01), Zn (p = 0.05) and Cu (p < 0.01). Liver iron content correlated significantly with total fat level (p = 0.03).

Relative and combined roles of ethanol and protein malnutrition on muscle zinc, potassium, copper, iron, and magnesium.

The aim of the present study is to analyse the relative and combined effects of ethanol and protein malnutrition on muscle zinc, copper, iron, potassium, and magnesium in ethanol-fed rats. The study was performed in 32 animals divided into four groups, fed with the Lieber-DeCarli control, 36% ethanol, 2% protein, and 36% ethanol 2% protein containing diets, respectively. Right gastrocnemius muscle was removed 2 months later, and was studied both chemically and histochemical-morphometrically. Both muscle zinc and potassium, but not copper nor iron nor magnesium, were significantly decreased in the protein-deprived, ethanol-fed animals, the main effect of these variations being attributable to ethanol rather than to protein deprivation. However, coexisting protein deprivation aggravated the decrease in both muscle zinc and potassium. Both muscle zinc and potassium were significantly related to serum albumin, weight loss, and type IIb fibre atrophy; and muscle zinc, in addition, to the decrease in type IIb fibre proportion. Therefore, a decrease in muscle content of both elements is related to histochemical-morphometrical changes observed in alcoholic myopathy. In addition, both ethanol and protein deficiency exerted independent, highly significant effects both on type IIb fibre atrophy and proportion.

Combined effects of ethanol and protein deficiency on hepatic iron, zinc, manganese, and copper contents.

The present study has been performed in order to establish the relative and combined roles of ethanol and malnutrition on liver Fe, Zn, Cu, and Mn alterations in alcoholic male adult Wistar rats, and also the relationships between these alterations and histomorphometrically determined hepatocyte and nuclear areas, perivenular fibrotic rim area, and total amount of fat present in the liver. Four groups of 8 animals each were fed: (1) a nutritionally adequate diet (C); (2) a 36% ethanol-containing (as percent of energy), isocaloric diet (A); (3) a 2% protein-containing, isocaloric diet (PD); and (4) a 36% ethanol, 2% protein-containing, isocaloric diet (A-PD), respectively, following the Lieber-DeCarli model. Ethanol-fed, protein-deficient animals showed the highest liver Fe, and the lowest Zn and Cu values, although differences in liver Zn, Mn, and Cu values were not significantly different between PD and A-PD groups. Statistically significant differences of these parameters were observed between the A and the A-PD groups, and between the A and PD groups, except for liver iron. Except for liver Mn, differences between C and A groups were statistically significant. These alterations correlated with liver fibrosis and steatosis, serum albumin, and weight loss, except for liver Mn, which was not correlated with fibrosis or steatosis. Thus, protein deficiency seems to enhance ethanol-induced liver Fe, Zn, and Cu alterations, whereas protein deficiency, but not ethanol, seems to play a major role on liver Mn alterations.

Effect of ethanol on hepatic iron, copper, zinc and manganese contents in the male albino mouse.

Liver Fe and Cu contents (determined by atomic absorption spectrophotometry) were found to be higher in alcoholized male albino mice than in controls. Alcoholized animals killed at the 180th day of life also showed higher liver Fe and Cu contents than the alcoholized animals sacrificed at the 85th day of life. A significant correlation was established between liver Fe content and size of the pericentral hepatocytes and their nuclei. No differences between alcoholic and controls were obtained regarding liver Zn content, whereas Mn showed a clear tendency to be higher in the alcoholics.

Effects of ethanol and propylthiouracil on hepatic iron and copper contents in the male albino mouse.

With the aim to analyze whether propylthiouracil (PTU) alters ethanol-induced changes in liver iron and copper contents, 40 male albino mice were equally divided into a control group, an ethanol-treated group, a PTU-treated group and an ethanol + PTU-treated group. Twenty animals were killed at the age of 85 days and 20 at the age of 180 days. Liver iron and copper contents showed a progressive, statistically non-significant increase both in the controls and in ethanol-treated animals. Liver iron contents was significantly higher in the 180-day-old alcoholic mice as compared with controls. Animals treated either with PTU or with PTU + ethanol showed liver iron levels in the normal range, markedly different from the ethanol-treated animals (P less than 0.005). Liver copper content of the ethanol-treated animals was higher (but not significantly) than that of the controls. Liver copper levels of the PTU + ethanol-treated animals were in the range of the ethanol-treated animals. Thus, PTU seems to revert an overload of ethanol-mediated iron of copper.