Slavko Kevrešan

NITROGEN AND PROTEIN METABOLISM IN YOUNG PEA PLANTS AS AFFECTED BY DIFFERENT CONCENTRATIONS OF NICKEL, CADMIUM, LEAD, AND MOLYBDENUM

A comparative study was carried out on the effect of molybdenum (Mo), nickel (Ni), cadmium (Cd), and lead (Pb) using concentrations of 1×10− 7, 1×10− 5, and 1×10− 3 mol dm− 3, on the metabolism of nitrogen and proteins in young pea plants (Pisum sativum L. ‘NS Lim’). The highest concentrations of the investigated metals were noted to suppress the development of the aboveground parts and roots. The smallest inhibiting effect was observed in the presence of Ni, which at lowest concentration produced a stimulating effect; Pb and Cd had a similar effect. The most pronounced inhibition was caused by Mo, which decreased the growth of the roots and aboveground parts by 50% and 35%, respectively. An increase in concentration of heavy metals in the medium resulted in their increased accumulation in both the plant roots and aboveground parts. The largest accumulation in the aboveground parts was observed for Ni and Mo, followed by Cd, and least for Pb. Nitrate and protein metabolism decreased according to the order of Cd > Pb > Ni > Mo. However, when expressed per amount of heavy metal accumulated in particular plant parts, toxicity was in the order of Pb > Cd > Ni > Mo.

Pharmacology of bile acids and their derivatives: absorption promoters and therapeutic agents.

SummaryThe role of bile acids in pharmacotherapy is reviewed in this article. The therapeutic use of bile has been recognized since ancient times. Previously bile acids were the standard treatment for gallstones where chenodeoxycholic acid and ursodeoxycholic acid were effective in promoting the dissolution of cholesterol gallstones. Today their therapeutic role looks set to expand enormously. Bile acids as absorption promoters have the potential to aid intestinal, buccal, transdermal, ocular, nasal, rectal and pulmonary absorption of various drugs at concentrations that are non-toxic. Keto derivatives of cholic acid, such as 3a, 7a, dihydroxy-12-keto-5a-cholic acid (sodium salt and methyl ester) are potential modifiers of blood-brain barrier transport and have been shown to promote quinine up-take, enhance the analgesic effect of morphine and prolong the sleeping time induced by pentobarbital. They have also been shown to be hypoglycaemic. Bile acids as therapeutic agents have the potential to produce beneficial effects in sexually transmitted diseases, primary biliary cirrhosis, primary sclerosing cholangitis, gallstones, digestive tract diseases, cystic fibrosis, cancer and diabetes.

Effect of heavy metals on nitrate and protein metabolism in sugar beet

Nitrate content, activities of nitrate reductase and glutamine synthetase, soluble protein content, and proportion of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBPCO) protein in total proteins were measured in leaves of Beta vulgaris L. plants affected by nickel, cadmium, and molybdenum in concentrations of 10-4, 10-2, and 1 mM. The most harmful effect on the above mentioned parameters had Cd, less harmful Ni, whereas Mo stimulated the investigated parameters. The proportion of RuBPCO protein showed a high tolerance to heavy metals.

Nitrogen and Azotobacter chroococcum enhance oxidative stress tolerance in sugar beet

After treatment with increased quantities of nitrogen and Azotobacter strains, activities of antioxidant enzymes superoxide dismutase, peroxidase and catalase, content of chlorophylls and carotenoids, soluble proteins and dry matter in leaves of sugar beet increased.

Modeling and prediction (correction) of partition coefficients of bile acids and their derivatives by multivariate regression methods.

Different multiple regression methods including forward stepwise multiple linear regression (MLR), principal component regression (PCR) and partial least squares (PLS) have been applied to the modeling of partition coefficient (lipophilicity) of bile acids and their derivatives by means of 16 different descriptors obtained by using Alchemy package software and retention index R(Mo) as an experimental estimation of lipophilicity. Retention indices for bile acids and their derivatives were determined by reversed phase high-performance thin layer chromatography on RP-18 W bounded stationary phase with methanol-water in different volume proportions as mobile phase. The results achieved concerning the prediction of Log P are highly significant and consistent with the molecular structure of the compounds investigated. The sum of absolute values of the charges on each atom of the molecule, in electrons (SQ), the sum of absolute values of the charges on the nitrogens and oxygens in the molecule, in electrons (SQ(NO)), specific polarizability of a molecule (SP), the third-order connectivity index ((3)chi) and molecular lipophilicity, seem to be dominant in the partition mechanism. In addition, regression models developed have allowed a correct estimation of the partition coefficients of cholic acid (Log P(HA)=2.93; Log P(A)(-)=2.02) as compared with reported experimental values (Log P(HA)=2.02; Log P(A)(-)=1.1).

Formation of hydrogen-bonded complexes between bile acids and lidocaine in the lidocaine transfer from an aqueous phase to chloroform.

Bile acids are amphiphilic molecules, which, in addition to their physiological role, have also acquired increasingly more important pharmacological applications. It has been shown that these compounds have a promoting effect on the transport of many drugs through the cell membrane. Pharmacodynamic studies showed that they exerted a significant effect on the analgesic action of lidocaine. This study is concerned with the determination of the constants of hydrogen-bonded complexes formed between the investigated bile acids and lidocaine. It was found that a prerequisite for forming such a complex is the existence of at least two OH groups or one OH group and one keto group in the bile acid molecule at an appropriate mutual distance. If a keto group is involved in lidocaine binding, the resulting complex has a larger equilibrium constant. A model--multiple linear regression equation--was constructed, relating the molecular descriptors to the equilibrium constant of hydrogen-bonded complex. It was also shown how the complex formed between lidocaine and bile acid influences the rate constant of the decrease of lidocaine concentration in the aqueous phase during its transfer to the chloroform solution of a bile acid. It was found that the complex formed between lidocaine and bile acids plays an important role in the appearance of the depot effect of lidocaine.

Effect of cholic acid and its keto derivatives on the analgesic action of lidocaine and associated biochemical parameters in rats.

SummaryThis study examined the effect of the structure and concentration of cholic acid and its keto derivatives on the local analgesic action of lidocaine in rats, measured by an analgesimetric method. The increase in bile acid concentrations in the administered lidocaine solution increased the duration of local anesthesia. It was found that the introduction of keto groups into the cholic acid molecule yielded derivatives with lower promotory action, i.e. decreased the duration of local anesthesia. The biochemical parameters investigated indicated that the keto derivatives of cholic acid exhibited no toxicity compared to that of cholic acid itself.

Dynamics of cadmium distribution in the intercellular space and inside cells in soybean roots, stems and leaves

Soybean (Glycine max L.) plants grown in nutrient solution were exposed to 1 mM Cd(NO3)2 for 24 h. Dynamics of distribution of cadmium among its different forms (water soluble, Ca-exchangeable and complexed) in the intercellular space and the ratio of the intercellular and intracellular cadmium in roots, stems and leaves were studied. In roots, in the beginning of treatment the largest portion of Cd was found in the intercellular space and 1 h later Cd content started to decrease, so that between 13- and 24-h treatment an equilibrium was reached in which about 70 % of Cd was found inside cells. In stems, already after 1-h treatment, the Cd concentrations in the cells and intercellular space were similar, the equilibrium being disturbed after 13 h, so that after 24-h treatment 80 % of Cd was found inside cells. In leaves, up to the 13 h Cd distribution showed fluctuation, after that equilibrium was reached, with 70 % of intracellular Cd. The highest contents of all Cd forms in the intercellular space was observed in roots.

Effect of stevioside and sodium salt of monoketocholic acid on glycemia in normoglycemic and diabetic rats

SummaryThis study investigated the effect of a commercial preparation of stevioside and a synthetic compound, sodium salt of monketocholic acid (MKC), administered per os (p.o.) and also adminstered via an osmotic pump, on glycemia in normoglycemic and diabetic Wistar rats. Diabetes was induced with alloxan, 100 mg/kg, i.p. Normoglycemic and diabetic rats were treated p.o. for five days either with physiological solution (1 ml/kg, controls), stevioside (20 mg/kg), MKC (4 mg/kg) and a combination of stevioside (20 mg/kg) and MKC (4 mg/kg). Apart from p.o. adminstration, stevioside and MKC were also administered via a subcutaneously (s.c.) implanted osmotic pump. During treatment and upon termination of the latter, glycemia was measured and the rats that were treated p.o. were subjected to the oral glucose tolerance test (OGTT) at a dose of 1 g/kg. Following this animals were anesthetized with urethane (0.75 g/kg, i.p.) and killed by cardiopunction to determine C-peptide levels in the serum. In all three groups of normoglycemic rats highest decrease in glucose levels was observed on the fourth day of the experiment. The stevioside + MKC combination showed a stronger hypoglycemic effect compared to individual treatments with stevioside and MKC (3.73:4.80:4.73 mmol/L). In the group of diabetic rats that received both substances via the osmotic pump, the hypoglycemic action was also stronger compared to the individual treatments with stevioside and MKC (16.15:18.89:18.75 mmol/L). The treatment of healthy rats with both substances p.o. caused no statistically significant difference in glycemia, whereas in diabetic rats the combination of stevioside + MKC showed a statistically significant decrease in glycemia compared to control values. In both groups of rats, treatment with stevioside and MKC and their combination prevented an increase in glucose concentrations in the OGTT. Only the administration of stevioside by osmotic pump yielded a statistically significant increase in the concentrations of C-peptide in the serum of healthy rats. Compared to controls, the concentrations of C-peptide in diabetic rats were significantly higher after treatment with either stevioside or its combination with MKC, irrespective of the mode of administration.

Critical micellar concentrations of keto derivatives of selected bile acids: Thermodynamic functions of micelle formation

The knowledge of the process of formation of molecular aggregates of bile acids in aqueous media and of the corresponding critical micellar concentrations (CMCs) is of great significance because of the biological importance of these compounds and their pharmacological applications. In view of this, the present study is concerned with the determination of CMCs of cholic and chenodeoxycholic acids and their keto derivatives at different temperatures with the aim to calculate the standard thermodynamic functions of micelle formation. Based on the molecular descriptors for tested compounds and entropy of micelle formation, the method of principal component analysis (PCA) allowed grouping of the behavior of tested molecules at 30, 50 and 70 degrees C. To one group belong cholic acid and its keto derivatives, the other group consisting of chenodeoxycholic and deoxycholic acids and their keto derivatives. For each group, the derived multiple linear regression equations of the entropy dependence on temperature contains different independent variables. A main difference between the two groups of tested bile acids is in the energy of dipole-dipole interaction, which appears to be temperature dependent, and in the case of the latter group comes into play as an independent variable already in the regression equation derived for 30 degrees C. The most remarkable changes of the descriptors with temperature were observed in the group of cholic acid and its derivatives.