Cardioprotective and Hepatoprotective Potential of Silymarin in Paracetamol-Induced Oxidative Stress.

Silymarin, derived from Silybum marianum, has been used in traditional medicine for various ailments. In this study, the cardioprotective and hepatoprotective effects of silymarin against paracetamol-induced oxidative stress were examined in 28 male Swiss Webster mice, divided into four groups and treated for 7 days (via the oral route) with (a) saline 1 mL/kg (control group), (b) saline 1 mL/kg + single dose of paracetamol 110 mg/kg on the 7th day; (c) silymarin 50 mg/kg; and (d) silymarin 50 mg/kg + single dose of paracetamol 110 mg/kg on the 7th day. In vitro and in vivo antioxidant activity together with liver enzyme activity were evaluated. Histopathological and immunohistochemical assessment was performed. Silymarin mitigated paracetamol-induced liver injury by reducing oxidative stress markers such as lipid peroxidation and restoring antioxidant enzyme activity. Silymarin treatment resulted in a significant decrease in liver enzyme levels. Reduced necrosis and inflammatory infiltrate in liver tissues of silymarin-treated groups were detected as well. Immunohistochemical analysis demonstrated reduced expression of inflammatory markers (COX2, iNOS) and oxidative stress marker (SOD2) in the liver tissues of the silymarin-treated groups. Similar trends were observed in cardiac tissue. These results suggest that silymarin exerts potent hepatoprotective and cardioprotective effects against paracetamol-induced oxidative stress, making it a promising therapeutic agent for liver and heart diseases associated with oxidative damage.

Carob Extract (Ceratonia siliqua L.): Effects on Dyslipidemia and Obesity in a High-Fat Diet-Fed Rat Model.

Dyslipidemia and obesity are recognized as two of the major global health issues and main risk factors for coronary heart disease and cerebrovascular disease. In recent years, carob has shown certain antioxidant and anti-dyslipidemic potential. In this study, Wistar rats were fed with a standard and cholesterol-enriched diet and treated orally with carob extract and simvastatin for four weeks. After sacrifice, blood samples were collected for biochemical analysis, and liver tissue was taken for histological and immunohistochemical assessment. Weight gain was significantly higher in groups fed with cholesterol-fortified granules; total cholesterol was found to be significantly lower in the hypercholesterolemic groups treated with simvastatin and simvastatin/carob combined regimens compared with hypercholesterolemic animals treated with saline (p < 0.05). The same was true for low-density lipoprotein cholesterol and the LDL/HDL ratio (p < 0.05). Adiponectin was remarkably higher in animals treated with simvastatin compared to all other groups (p < 0.05). Leptin was significantly lower in groups treated with carob and simvastatin compared to the hypercholesterolemic group treated with saline (p < 0.05). Carob/simvastatin co-administration reduced hepatocyte damage and improved liver morphology. A study confirmed the anti-dyslipidemic, anti-obesity, and hepatoprotective potential of carob pulp alone or in combination with simvastatin in the treatment of high-fat diet-fed rats.

PHARMACOVIGILANCE IN SERBIA: A TEN-YEAR PHARMACOEPIDEMIOLOGIC ANALYSIS.

Pharmacovigilance as a science and group of activities related to detection, collection, analysis, understanding and prevention of adverse drug reactions (ADRs) is an essential activity in the regulatory system of drugs of any country. Defining increased patient safety as the main purpose of ADR reporting, a well-designed national pharmacovigilance system achieves its ultimate goal, i.e., protection of public health. In organizational and technical terms, the Republic of Serbia has a well-developed system of pharmacovigilance, created on the basis of a proven reliable system of the former SFR Yugoslavia, and carried out by the National Agency for Medicines and Medical Devices of Serbia (ALIMS), which conducts all organized activities aimed at strengthening the national system of ADR monitoring and reporting. Unlike the neighboring Croatia and Montenegro with similar pharmacovigilance systems, Serbia has only recently approached the WHO standard of 200 reports per million inhabitants despite a significant increase of 180 ADR reports per million inhabitants in 2019 (1251 in total). Considering this, our study aimed to provide a critical insight into the practice of pharmacovigilance in Serbia by pharmacoepidemiologic analysis of a ten-year period of ADR monitoring and reporting activities.

Community pharmacists' challenges regarding adverse drug reaction reporting: a cross-sectional study.

OBJECTIVE: The effectiveness of the national drug safety monitoring program directly depends on the active participation of healthcare professionals in reporting suspected adverse drug reactions (ADRs). The aim of the study was to explore community pharmacists' comprehension of pharmacovigilance, their perspectives toward reporting ADRs and investigate the current practice of ADR reporting among pharmacists in Serbia. METHODS: This descriptive cross-sectional study was performed on a sample of pharmacists in Serbia between November 2019 and March 2020 using a pre-tested questionnaire distributed online. Eligible participants were community pharmacists in Serbia who were willing to participate in the study during the data collection period. Non-parametric statistical tests were performed in the analysis of knowledge, perspectives and ADR reporting. The validity and reliability of the survey were measured by exploratory factor analysis. RESULTS: The median knowledge score was 6 out of 10 (interquartile range 5-7, range 2-10). No significant differences in the knowledge scores of pharmacists were found based on weekly working hours (U = 24,805, p = .374), working experience (χ2 = 4.011, DF = 2, p = .135), being a member of a professional organization (U = 24,312, p = .209), or highest level of pharmacy qualification obtained (χ2 = 3.233, DF = 3, p = .506). Only 28.8% of pharmacists reported ADR at least once a year, while the majority of them have never reported any ADRs. CONCLUSIONS: Despite the community pharmacists' positive attitude toward adverse drug reporting and their role in the process, they show limited knowledge regarding the issue and highly prevalent under-reporting of ADRs. Educational programs are necessary to increase ADRs reporting.

Hepatoprotective Effect of Carob Pulp Flour (Ceratonia siliqua L.) Extract Obtained by Optimized Microwave-Assisted Extraction.

To examine antioxidant capacity and the hepatoprotective effect of carob pulp flour, microwave-assisted extraction was performed. The influence of ethanol concentration (0-40% w/w), extraction time (5-25 min) and irradiation power (400-800 W) on DPPH, FRAP and ABTS antioxidant activity of carob pulp flour extract was evaluated. The strongest influence was that of the ethanol concentration, followed by extraction time. Optimal process parameters for maximizing total antioxidant activity were determined, using response surface methodology: ethanol concentration 40%, time 25 min and power 800 W. Carob extract obtained at optimal conditions (CE) was analyzed in vivo using a paracetamol-induced hepatotoxicity model in mice. Treatment with CE attenuated the parameters of liver injury, especially aspartate and alanine aminotransferase activity, and prevented paracetamol-induced increase in malondialdehyde levels. Pretreatment with CE reversed the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase enzymes after the high dose of paracetamol in the liver. Hepatotoxicity induced using a toxic dose of paracetamol was also seen through histopathological alterations, which were significantly reduced in the groups treated with CE prior to paracetamol. Still, the number of Kupffer cells and macrophages did not differ among groups. Finally, pretreatment of mice with CE and paracetamol significantly decreased the expression of cytochrome P450 2E1 (CYP2E1) in hepatocytes.

Pharmacological effects of novel microvesicles of basil, on blood glucose and the lipid profile: a preclinical study.

Microencapsulation represents a process that can create targeted, controlled release kinetics of drugs, thus optimizing therapeutic efficacy. Our group has investigated the impact of this technology on Wistar rats to determine pharmacological efficacy of basil extracts. Animals were treated with water extract of Ocimum basilicum in microvesicles and with combination of basil extracts and 3α,7α-dihydroxy-12-keto-5-cholanate, also known as 12-monoketocholic acid (MKC) acid in microvesicles for 7 days. Alloxan was used to induce hyperglycemia. Pharmacological effects on glycemia were evaluated by measuring blood glucose levels in alloxan-induced diabetic rats. Microvesicles were prepared using the Büchi-based microencapsulating system developed in our lab. The dose of basil extract that was orally administered in rats was 200 mg/kg and the dose of MKC acid was 4 mg/kg as per established protocols. A seven-day treatment with basil aqueous extract, as well as a combination of basil and MKC acid extract in the pharmaceutical formulation, led to a statistically significant reduction in the blood glucose concentration of animals with alloxan-induced hyperglycemia compared to pre-treatment values (p < 0.05 and p < 0.01), which indicates that basil has hypoglycemic and antihyperglycemic effects. Microvesicles, as a pharmaceutical-technological formulation, substantially enhance the hypolipidemic action of basil extract with MKC acid.

Experimental and Computational Evaluation of Extraction Procedure and Scavenging Capacity of Sweet Basil Extracts (Ocimum basilicum L.).

The possibility to prevent nutrition-related diseases that include scavenge of free radicals and to block chain reactions is very important and significant for human well-being. The aim of this study was to analyse different basil extracts, determine the relationship between total phenolic/flavonoid content and antioxidant activity in order to optimize its application in industry. The extraction involved different solvents (ethanol, methanol and water), extraction time (10 and 30 min and 24, 48 and 72 h), plant fragmentation level (0.3 and 2 mm) and the presence or absence of light. Antioxidant activity was investigated by applying spectrophotometric method and measuring the total phenolic and flavonoid content and DPPH radical scavenging activity. The content of total phenolics varied from 5.2 to 185.6 mg of gallic acid equivalents per gram of a dry extract and flavonoids ranged from 0.2 to 35.0 mg of quercetin per gram of a dry extract. All extracts presented a scavenging capacity and IC50 values of DPPH radical inhibition ranged from 0.04 to 12.99 µg/ml. The evaluation of experimental data for eighty basil extracts was performed by chemometric analysis showing good correlation between yield and total phenolic compounds, as well as flavonoid content and inhibition of the DPPH radical.

Phytochemical characterization and effects on cell proliferation of Pinus nigra Arn. bark.

Pinus nigra Arn. bark extracts from Mokra gora (MG) and Tara mountains were analyzed with regard to their polyphenolic profile and antioxidative and antiproliferative activity. The ethanol extract from MG showed the highest phenolic, flavonoid, tannin, and proanthocyanidin content when compared with the acetone and methanol extracts from both sites. The same extract exhibited the highest ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) and ferric reducing antioxidant power (FRAP) radical scavenging ability and total antioxidant activity (TAA). On the basis of high-performance liquid chromatography analysis, catechin, caffeic, syringic, p-coumaric, and ferulic acids were predominantly present in the MG extracts. The ethanol extract from MG was rich in syringic acid, epicatechin and its derivatives, and ferulic acid and its derivatives. The bark extracts also exerted a high cytotoxic bioactivity against all evaluated cell lines (HeLa, MCF7, HT-29, and MRC-5). The antiproliferative activity of P. nigra bark is probably related to the ferulic acid content and its synergistic activity to caffeic acid and taxifolin. The antioxidative role of the presented phenols was confirmed through the obtained significant linear correlation between the total phenolic content and DPPH (r = .934) as well as the FRAP% of the extracts (r = .948). Also, the TAA significantly depended on the proanthocyanidins (r = .902) and tannin contents (r = .914). The composition of the presented compounds could be related to promising antioxidant and antiproliferative efficacy of MG bark.

Chemical composition, nutritional profile and in vivo antioxidant properties of the cultivated mushroom Coprinus comatus.

This study investigated the chemical and nutritional profile and antioxidative properties of cultivated Coprinus comatus. Proximate analysis revealed that C. comatus is rich in carbohydrates, dietary fibres and proteins, and could also be a valuable source of phenolics. Additionally, fat content is low, consisting mainly of polyunsaturated and omega-3 fatty acids. Furthermore, the safety profile of C. comatus is satisfactory, with all elements of toxicological importance within the proposed limits. Oral treatment with C. comatus for 42 days improved the antioxidant capabilities and ameliorated carbon tetrachloride-induced liver damage in rats, marked by decreased serum aminotransferase levels and lipid peroxidation intensity. Glutathione concentrations increased in a dose-dependent manner. Histological morphometric and immunohistochemical analysis confirmed antioxidative and hepatoprotective potential. These findings imply that cultivated C. comatus could be considered a nutraceutical, having beneficial nutrient and therapeutic properties.

Binary polymeric amorphous carvedilol solid dispersions: In vitro and in vivo characterization.

Binary polymeric amorphous carvedilol solid dispersions were prepared using solvent method by varying solvent type, polymer type and carvedilol to polymer ratio in order to assess the influence of these factors and maximize carvedilol dissolution rate. Low and high molecular weight polyvinylpyrrolidone, polyvinylpyrrolidone-vinyl acetate copolymer and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer were used as polymeric carriers in carvedilol to polymer ratios 1:1, 1:2 or 1:4, while absolute ethanol or acetone were used as solvents. Hard gelatin capsules were prepared with carvedilol solid dispersion and lactose monohydrate, mannitol or microcrystalline cellulose. FTIR and PXRD were used to detect carvedilol crystallinity and identify carvedilol-polymer interactions and carvedilol polymorphs. These techniques confirmed carvedilol transition to amorphous state and suggested that hydrogen bonds were formed between carvedilol and polymer molecules. Carvedilol dissolution rate was significantly higher from solid dispersions with higher carvedilol to polymer ratio and solid dispersions prepared using the solvent in which the polymer was more soluble. Solid dispersion with polyvinylpyrrolidone-vinyl acetate copolymer in 1:4 ratio in absolute ethanol displayed the highest carvedilol dissolution rate with 91.78% carvedilol dissolved in the first 30 min. Capsules prepared with the selected solid dispersion and microcrystalline cellulose as diluent displayed the highest carvedilol dissolution rate, with 93.43% carvedilol dissolved within the first 30 min. Carvedilol bioavailability was significantly increased by formulating solid dispersions, while the analysis of serum biochemical parameters excluded damage on liver and kidney function and the lipid profile of animals exposed to investigated drug delivery system.

Antinociceptive activity of Thyme (Thymus vulgaris L. ) and interactions with neurotropics and analgesics

The plant world represents an important source of potential therapeutic agents, but concomitant administration of herbal and conventional medications may result in interactions with subsequent beneficial or adverse effects. This study was designed to examine the analgesic effect of thyme tincture and thyme syrup, two commonly used thyme formulations, and their interactions with codeine, paracetamol, pentobarbital and diazepam in mice. The identification and quantification of thymol and carvacrol were carried out by GC/MS and GC/FID. The analgesic activity was studied using a hot plate method. Effects of thyme syrup on diazepam-induced motor coordination impairment in rotarod test and on pentobarbital-induced sleeping time were also determined. Thymol (175.3 µg/mL and 9.73 µg/mL) and carvacrol (10.54 µg/mL and 0.55 µg/mL) concentrations were measured in tincture and syrup, respectively. Thyme syrup and tincture exhibited effective analgesic activity in the hot plate pain model. Pretreatment with thyme formulations reduced analgesic activity of codeine, and potentiated the analgesic activity of paracetamol. Co-administration of thyme formulations has led to potentiation of diazepam and pentobarbital depressive central nervous system effects. Thyme formulations interacted with tested conventional drugs, probably through interference with their metabolic pathways and succeeding altered concentrations and pharmacological effects.

Appropriate antibiotic prescribing among final-year medical students in Europe.

Little is known about undergraduate education on antibiotic prescribing in Europe and even less about the antibiotic prescribing skills of nearly-graduated medical students. This study aimed to evaluate the antibiotic prescribing skills of final-year medical students across Europe and the education they received during medical training. In a cross-sectional study, final-year medical students from 17 medical schools in 15 European countries were asked to prescribe for two written case reports of infectious diseases (acute bronchitis and community-acquired pneumonia). The appropriateness of antimicrobial therapy was determined using a scoring form based on local guidelines. Teachers from each medical school were asked to complete a standardised questionnaire about the teaching and assessment of undergraduate education on antibiotic use. In total, 856 final-year medical students (95.6%) completed the assessment and 16 teachers (94.1%) completed the questionnaire. Overall, 52.7% (range 26-83%) of the 1.683 therapies prescribed were considered appropriate. The mean number of contact hours for undergraduate education on antimicrobials was 25.6 (range 2-90). Differences in education styles were found to have a significant impact on students' performance, with a problem-based learning style being associated with more appropriate antimicrobial prescribing than a traditional learning style (46.0% vs. 22.9%; P < 0.01). Although there are differences between medical schools, final-year medical students in Europe lack prescribing skills for two common infectious diseases, possibly because of inadequate undergraduate education on antibiotic use and general prescribing. To improve students' skills, interactive teaching methods such as prescribing for simulated and real patients should be used.

Resveratrol supplementation improves metabolic control in rats with induced hyperlipidemia and type 2 diabetes.

Resveratrol was recognized as the major factor responsible for the beneficial properties of red wine. Several resveratrol-based dietary supplements are available, but their efficacy has not been sufficiently tested. This study was designed to examine the effect of resveratrol supplementation, using a commercially available product, on the metabolic status of experimental animals with induced hyperlipidemia or type 2 diabetes mellitus (T2DM). Hyperlipidemia was induced by feeding the rats a standard pellet diet supplemented with cholesterol. T2DM was induced by adding 10% fructose to drinking water and streptozotocin. Treatment with resveratrol-based supplement improved glycemic control in diabetic animals and significantly decreased serum low-density-lipoprotein (LDL) and triglyceride levels, concurrently increasing the high-density-lipoprotein (HDL) levels in animals with hyperlipidemia. Resveratrol-treated animals had improved tolerance to glucose loading. Supplementation did not induce alterations in parameters of liver and renal function. Findings indicate that commercial resveratrol supplement improves metabolic control in rats with induced hyperlipidemia and T2DM.

Hepatoprotective and antioxidant potential of Pycnogenol® in acetaminophen-induced hepatotoxicity in rats.

Pycnogenol® (PYC) has already being used as a food supplement and herbal medicine due to its potent antioxidant properties. The aim of the present study was to examine the protective effect of PYC on acetaminophen-induced acute liver injury in rats. The effect of PYC on acetaminophen-induced hepatotoxicity in rats was examined by determining biochemical parameters, in vitro antioxidant activity, histological assessment, and oxidative status in liver homogenates. The best antioxidant properties were demonstrated in methanolic extracts. Seven-day pretreatment with PYC suppressed elevation of CYP2E1 protein expression induced by administration of toxic dose of acetaminophen. PYC at 50 mg/kg showed the ability to significantly decrease malondialdehyde (MDA) level compared with the group received acetaminophen. Xanthine oxidase (XOD) enzyme activity was significantly elevated in acetaminophen-treated group compared with control, whereas concomitant administration of PYC in a dose of 50 mg/kg significantly reduced activity of this enzyme. Significant decrease of glutathione (GSH) hepatic content in acetaminophen-intoxicated rats compared with the control rats was improved by concomitant administration of PYC at 50 mg/kg. Protective effect of PYC on acetaminophen-induced acute liver injury in rats has showed the best in vitro antioxidant potential expressed in methanolic extract and consequent histological assessment and oxidative status in liver homogenates.

The influence of standardized dry ivy leaf extract on the proportion of nasal secretion after post-septoplasty nasal packing removal.

INTRODUCTION: After post-septoplasty nasal packing removal, a certain proportion of nasal secretion occurs, leading to local and sometimes systemic infections. OBJECTIVE: The aim was to determine if standardized dry ivy leaf extract application after nasal packing removal influences the reduction of nasal secretion and diminish the occurrence of local infections. METHODS: The study included 70 post-septoplasty patients (divided into two equal groups) whose nasal packing was removed on the third day after the procedure. Group I was treated with standardized dry ivy leaf extract syrup along with regular nasal irrigation for the five days after the nasal packing removal whereas the Group II had only nasal lavage. On the sixth day after nasal packing removal, the quantity of nasal secretion was determined using a visual analog scale and nasal endoscopic examination. RESULTS: The group treated with standardized dry ivy leaf extract syrup had significantly lesser nasal secretion both by subjective patients' assessment (p<0.001) and by nasal endoscopic examination (p=0.003). The post-surgical follow up examination on the sixth day after nasal packing removal showed no development of local infection in the Group I, while in the Group II a local infection was evident in five patients (14.29%) and antibiotic therapy was required. CONCLUSION: The use of the standardized dry ivy leaf extract after nasal packing removal significantly lowers the proportion of nasal secretion.

Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats.

Semisolid self-microemulsifying drug delivery system (SMEDDS) with optimized drug loading capacity, stability, dispersibility in aqueous media and in vitro drug release profile, was evaluated in vivo regarding effects on pharmacokinetics of acyclovir, an antiviral with low bioavailability (BA) and short half-life (t1/2). Additional goal of this study was evaluation of safety of this semisolid SMEDDS consisted of medium chain length triglycerides (oil) (10% w/w), macrogolglycerol hydroxystearate (surfactant) (56.25% w/w), polyglyceryl-3-dioleate (cosurfactant) (6.25% w/w), glycerol (cosolvent) (20% w/w), macrogol 8000 (viscosity modifier) (7.5% w/w), and acyclovir (2.5 mg/ml). The study was performed on fully mature white male Wistar rats. The pharmacokinetics of acyclovir was monitored in three groups (1-3) of animals after administration of drug solution (intravenously (IV)), drug suspension (orally) and semisolid SMEDDS (orally), respectively. The determined pharmacokinetic parameters were: maximum concentration of acyclovir in serum (Cmax), time taken to reach Cmax (Tmax), areas under time-concentration curves (AUC0-t and AUC0-∞), terminal elimination rate constant (kel), t1/2, volume of distribution (Vd), mean residence time (MRT), clearance (Cl), zero concentration (C0), steady state volume of distribution (Vss), and BA. Additionally, for safety evaluation, animals were treated orally with aqueous solution of acyclovir, drug-free semisolid SMEDDS and acyclovir-loaded semisolid SMEDDS, during 21 days (groups 4-7). Serum samples of sacrificed animals were used for biochemical analysis of enzymatic activity of alanine transaminase (ALT) and aspartate transaminase (AST), urea, creatinine, and uric acid. Acyclovir administered by semisolid SMEDDS reached twice higher Cmax (0.92 ±â€¯0.21 µg/ml) and has significantly shorter Tmax (14 ±â€¯10.84 min) compared to the suspension of acyclovir (Cmax 0.29 ±â€¯0.09 µg/ml and Tmax 26.00 ±â€¯5.48 min). BA of the drug was significantly increased by semisolid SMEDDS, while the analysis of biochemical parameters excluded damage on function of liver and kidneys caused by the investigated drug delivery system.

Antioxidative and Protective Actions of Apigenin in a Paracetamol-Induced Hepatotoxicity Rat Model.

BACKGROUND AND OBJECTIVES: Apigenin is known to have various pharmacological properties without causing significant toxicity; however, hepatoprotective effect of apigenin is not often reported. The aim of our study was to investigate if the alterations in lipid peroxidation and antioxidant status are in favor to prove the efficacy of apigenin against paracetamol-induced hepatotoxicity. METHODS: The effect of apigenin on paracetamol-induced hepatotoxicity in rats was examined by determining biochemical parameters, histological assessment and oxidative status in liver homogenates. RESULTS: The treatment of animals with both apigenin and paracetamol attenuates the parameters of hepatotoxicity, especially for ALT and ALP activity which was significantly lower compared to groups of animals treated with saline and paracetamol. Hepatotoxicity induced by toxic dose of paracetamol was revealed also by notable histopathological alterations, which were not observed in the group treated with paracetamol together with apigenin. Apigenin also prevented paracetamol-induced increase in malondialdehyde (MDA) level. The activities of both CAT (catalase) and GR (glutathione reductase) enzymes after the toxic dose of paracetamol were significantly increased in the liver homogenates, compared to control group. Apigenin reversed these parameters near to values of control group. CONCLUSIONS: The result of our study indicates that apigenin inhibits the level of lipid peroxidation and significantly increases the enzyme antioxidant defense mechanisms in paracetamol-induced hepatotoxicity in rats.

Effects of pharmaceutical formulations containing thyme on carbon tetrachloride-induced liver injury in rats.

BACKGROUND: Herbal supplements are widely used in the treatment of various liver disases, but some of them may also induce liver injuries. Regarding the infuence of thyme and its constituents on the liver, conflicting results have been reported in the literature. The objective of this study was to examine the influence of two commonly used pharmaceutical formulations containing thyme (Thymus vulgaris L.), tincture and syrup, on carbon tetrachloride-induced acute liver injury in rats. METHODS: Chemical composition of investigated formulations of thyme was determined by gas chromatography and mass spectrometry. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. Liver morphology was characterized by light microscopy using routine hematoxylin and eosin staining. RESULTS: Thymol was found to be predominant active constituent in both tincture and syrup. Investigated thyme preparations exerted antioxidant effects in liver by preventing carbon tetrachloride-induced increase of lipid peroxidation. Furthermore, co-treatment with thyme preparations reversed the activities of oxidative stress-related enzymes xanthine oxidase, catalase, peroxidase, glutathione peroxidase and glutathione reductase, towards normal values in the liver. Hepatotoxicity induced by carbon tetrachloride was reflected by a marked elevation of AST and ALT activities, and histopathologic alterations. Co-administration of thyme tincture resulted in unexpected exacerbation of AST and ALT values in serum, while thyme syrup managed to reduce activites of aminotransferases, in comparison to carbon tetrachloride-treated animals. CONCLUSIONS: Despite demonstrated antioxidant activity, mediated through both direct free radical scavenging and activation of antioxidant defense mechanisms, thyme preparations could not ameliorate liver injury in rats. Molecular mechanisms of diverse effects of thyme preparations on chemical-induced hepatotoxicity should be more in-depth investigated.

Effect of aqueous solution of stevioside on pharmacological properties of some cardioactive drugs.

BACKGROUND/AIM: Stevioside is a glycoside that supposedly possesses a number of pharmacodynamic effects such as anti-infective, hypoglycemic, along with the beneficial influence on the cardiovascular system. The aim of this study was to determine the effect of rats pretreatment with aqueous solution of stevioside on pharmacological actions of adrenaline, metoprolol and verapamil. METHODS: Rats were administered (intraperitoneally 200 mg/kg/day) stevioside as aqueous solution or physiological saline in the course of 5 days, then anaesthetized with urethane and the first ECG recording was made. The prepared jugular vein was connected to an infusion pump with adrenaline (0.1 mg/mL), verapamil (2.5 mg/mL) or metoprolol (1 mg/mL). Control animals, pretreated with saline, in addition to the mentioned drugs, were also infused with the solution of stevioside (200 mg/mL) in the course of recording ECG. RESULTS: The infusion of stevioside produced no significant changes in ECG, even at a dose exceeding 1,600 mg/kg. In the control group, a dose of adrenaline of 0.07 +/- 0.02 mg/kg decreased the heart rate, whereas in the stevioside-pretreated rats this occurred at a significantly higher dose (0.13 +/- 0.03 mg/kg). In stevioside-pretreated rats, the amount of verapamil needed to produce the decrease in heart rate was significantly lower compared to the control. The pretreatment with stevioside caused no significant changes in the parameters registered on ECG during infusion of metoprolol. CONCLUSION: The results suggest that pretreatment with stevioside may change the effect of adrenaline and verapamile on the heart rate.