Protein synthesis in rat liver after chronic ethanol treatment

8 TABLE

1

Influent PO at which pyridine nucleotide from phenobarbital-treated rats following

Lobular

Treatment Control Control

fluorescence anoxia

(5) (5)

Alcohol-treated* Alcohol-treated*

(6) (6)

increase

began in perfused

region

livers

PO,

(Torr)

Periportal Pericentral

178 290

+ 17t + 36

Periportal Pericentral

342 414

f 70 f 63

*Intubation with 5.0 g/kg at 2.5 hours prior to perfusion tMean 2 S.E.M.

(n).

170 pm) was constructed which could be placed in either region (300 500 pm in diameter) for the determination of pyridine nucleotide fluores-

cence (366 + 450 nm). When the 0s tension was decreased by switching to buffer saturated with a 95% Ns and 5% CO2 gas mixture, periportal and pericentral pyridine nucleotide systems became reduced at different inflow PO2 values (Table 1). In livers from control and alcohol-treated rats, pyridine nucleotides in the pericentral region were reduced at inflow PO2 values about 70 to 110 Torr greater than those in the periportal region. However, treatment with alcohol caused pyridine nucleotides in both periportal and pericentral regions to be reduced at inflow PO2 values 120 to 160 Torr higher than controls (Table 1). Under these conditions, oxygen uptake of the perfused liver of both groups was similar (105 to 112 pmoles/g per hour). These data provide direct physical evidence that alcohol-treated liver tissue is more susceptible to tissue anoxia in both periportal and pericentral regions. At least in phenobarbital-treated rats, this phenomena appears not to be due to an increase in oxygen uptake by the liver. These studies further demonstrate that the microlight guide can readily be applied to studies of intralobular metabolic compartment&ion. Supported, in part, by Grants AA-00033, AHA 79-1013.

AA-03624,

CA-23080 and

2 PROTEIN SYNTHESIS IN RAT LIVER AFTER CHRONIC ETHANOL TREATMENT ANNE

SMITH-KIELLAND*

Department of Pharmacology, Tromsd (Norway)

and JORG

Institute

MBRLAND

of Medical Biology,

University

of Tromsd,

9001

Effects of long-term ethanol treatment on protein synthesis in rat liver have been controversial. Most previous in viuo measurements have suffered

9

from lack of control over the specific radioactivity of the precursor amino acid during the incorporation period. In the present study the rate of protein synthesis was measured in anaestheiized rats, using a continuous, intravenous infusion of valine (specific radioactivity 3.33 pCi/mol), lasting for 30 min. The specific radioactivity of valine was measured to be fairly constant from 11 min onwards. Liver specimens were taken at 11, 20 and 30 min. The protein synthesis rate was calculated from valine-specific radioactivity in protein and in the intracellular precursor pool measured from 11 to 30 min. The rats were pair-fed either a diet containing ethanol (9.2 g/kg per rat per day) or a control diet, in which lipid replaced ethanol isoenergetically, for 58 - 65 days. The animal growth rate was not significantly different between the groups (2.8 g/day in the ethanol-treated US. 2.9 g/day in controls). All animals were fasted for approximately 16 h before measurement of protein synthesis. In addition, some rats received an i.p. injection (1 ml/kg) of either saline or dexamethasone (4 mg/kg) 1 h prior to measurement of protein synthesis. Chronic ethanol treatment reduced the in uiuo protein synthesis rate by 37% from a control rate of 86.0 + 5.9 nmoles valine per 100 g body weight per min (a = 0.002). This reduction became less marked when the rats received an i.p. injection of saline and disappeared completely when given dexamethasone i.p. 1 h before measurement of protein synthesis. Thus ethanol-treated rats given dexamethasone i.p. had a significantly higher rate of protein synthesis than ethanol-treated rats given nothing or saline (a < 0.05). Our observations demonstrate that the handling procedure preceding the measurement of protein synthesis could be of critical importance to the outcome of the experiments. This could explain some of the controversies in the literature on ethanol effects on rates of protein synthesis.

ZINC CONCENTRATIONS IN TWO STRAINS OF MICE AFTER CHOICE AND FORCED ETHANOL EXPOSURE JAMES

N. PASLEY*,

RICHARD

Departmenis of Physiology Arkansas Medical Sciences

E. STULL

FREE

and KIM E. LIGHT

and Biophysics and Biopharmaceutical Science, Campus, Little Rock, AR 72205 (II.S.A.)

University

01

Although the association of trace metal levels with the deleterious effects of chronic ethanol ingestion has been established for some time, reports have not implicated the preference for ethanol with trace metal concentrations in tissues. In this study we examined ethanol preference and trace metal concentrations in selected tissues of two strains of mice, the C57BL (an ethanol preferring strain) and CD1 (a relatively low ethanol preferring strain). Ethanol preference was determined by a three-bottle two-choice testing paradigm. In this design, animals were allowed access to three bottles: one contained a 5% (v/v) ethanol solution, one contained tap