Recent findings on the regulatory functions of CoA and the normalizing activity on plasma lipids of exogenous CoA.

In recent years many studies have shown that coenzyme A (CoA) is not only an acyl carrier coenzyme but it also has an important role in the regulation of metabolic functions and cell activities such as transport from the Golgi cisternae. This regulatory role is carried out by CoA, its precursor, catabolites and acylated derivatives. The acylation (myristylation and palmitylation) process of peptides and proteins dependent on CoA seems to be an important regulatory mechanism of cell activities. Furthermore exogenous CoA has been shown to decrease the triacylglycerols, cholesterol and Apo B of plasma lipoproteins in man. This regulatory mechanism acts either on VLDL synthesis and secretion or on their plasma clearance. CoA also protects cell-membrane and plasma lipoproteins against the peroxidative action of oxygen free-radicals.

Effect of coenzyme A on triglyceride and very-low-density lipoproteins secretion in cultured rat hepatocytes.

Exogenous coenzyme A (CoA) decreases plasma triglycerides, cholesterol, and Apo B in man. CoA regulates lipid metabolism favouring beta-oxidation in hepatic peroxisomes of very-long-chain fatty acids. Furthermore recent studies show that CoA participates in the transport processes which occur in the Golgi apparatus. The aim of this study was to establish whether exogenous CoA is able to modify the lipid composition of very-low-density lipoproteins (VLDL) and the VLDL secretion in rat hepatocyte culture. The presence of 5mM CoA produces a significant decrease of VLDL triacylglycerol, of VLDL total cholesterol and of VLDL esterified cholesterol by 32%, 39% and 41% respectively. This decrease is observed in all the three days of hepatocyte culture. On the third day a significant decrease of cytosolic triacylglycerols is also observed. The decrease in VLDL secretion depends on the concentration of CoA added to the culture medium. Our study shows that exogenous CoA decreases the plasma VLDL concentration because it reduces VLDL secretion by the hepatocytes.

Coenzyme A and hyperlipoproteinaemias.

Coenzyme A (CoA) exerts a favourable effect in lowering plasma lipids in patients with primary hyperlipoproteinaemias of phenotype IV (hypertriglyceridaemia) and of phenotype IIb (combined hyperlipidaemia). The mechanism by which CoA influences plasma lipids may be associated with the well-known role of this coenzyme in the catalysis of acylation reactions and in the control of lipid metabolism. The administration of CoA in animals fed on hyperlipidaemic diets reduces plasma lipid levels and causes a reduction of the hepatic concentrations of triglycerides and/or lipids. Mitochondria and peroxisomes isolated from liver of rats fed on a hyperlipidaemic diet and treated with CoA present an increased oxidation of palmitate. These results suggest that the primary effect of CoA is to increase fatty-acid oxidation in the liver that results in a decrease in endogenous synthesis of triglycerides as well as a reduced formation of VLDL and probably of cholesterol. The stimulation of fatty-acid oxidation in extrahepatic tissues may be also responsible for an increased catabolism of VLDL.

Recent advances of knowledge on the mechanism of action of drugs modifying the bronchial secretions.

In order to explain the mechanism of action of drugs modifying the bronchial secretions, their subdivision into agents with a direct or an indirect action seems justified: the former primarily modify already formed secretions, whilst the latter act on the bronchial structures originating mucus. In hypersecretive states with increased viscoelasticity of mucus, a widespread therapy is represented by the use of direct reducing drugs, which act by breaking the mucofibrillar network. Among them the most important are those with free sulphydryl groups (-SH), which can break the disulphide bonds of the bronchial secretions. The mechanism of action of substances such as acetylcysteine and tiopronin, that are included in those with a direct reducing action, was already verified by researches with the modified thrombo-elastograph (MTE) and has been recently confirmed by the present authors by employing a simple biochemical method, by which the action of such drugs on the structure of serum IgM can be studied in vitro. The same method permits the classification of carbocisteine and letosteine as amongst the drugs with indirect action. From the results obtained by such in vitro experiences, the necessity to examine more closely the consequences of secondary effects which direct mucolytic agents may cause by modifying the rheological, biochemical and immunological properties of bronchial secretions has been demonstrated.

Comparison between penetration of amoxicillin combined with carbocysteine and amoxicillin alone in pathological bronchial secretions and pulmonary tissue.

Patients with chronic bronchitis were treated orally with either amoxicillin (500 mg) alone or in combination with carbocysteine (150 mg), thrice daily for five days, in order to assess whether the combination allows higher antibiotic levels to be obtained in bronchial mucus than those obtained from amoxicillin alone. Serum and mucus levels were determined for each patient at first and fifth day of the two drug regimens. The levels of amoxicillin in the lung tissue collected in patients undergoing pulmonary surgery were also determined after a single oral dose of amoxicillin (1 g) or of amoxicillin (1 g) plus carbocysteine (300 mg). In the bronchial secretions, at the same plasma concentrations, amoxicillin levels were statistically higher after administration of combined substances. These findings indicate the presence of a pharmacokinetic synergism between these compounds, which allows amoxicillin to penetrate more easily through the hemato-bronchial barrier. The association of amoxicillin and carbocysteine, determining an increase of the quantitative levels of antibiotic in the bronchial secretion (also if it is purulent), performs a sterilizing action in a short time with significant therapeutic advantages.