Correction: Banjac et al. The Effects of Different Doses of Sildenafil on Coronary Blood Flow and Oxidative Stress in Isolated Rat Hearts. Pharmaceuticals 2023, 16, 118.

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Prehospital Trauma Scoring Systems for Evaluation of Trauma Severity and Prediction of Outcomes.

INTRODUCTION: Trauma scoring systems in prehospital settings are supposed to ensure the most appropriate in-hospital treatment of the injured. AIM OF THE STUDY: To determine the sensitivity and specificity of the CRAMS scale (circulation, respiration, abdomen, motor and speech), RTS score (revised trauma score), MGAP (mechanism, Glasgow Coma Scale, age, arterial pressure) and GAP (Glasgow Coma Scale, age, arterial pressure) scoring systems in prehospital settings in order to evaluate trauma severity and to predict the outcome. MATERIALS AND METHODS: A prospective, observational study was conducted. For every trauma patient, a questionnaire was initially filled in by a prehospital doctor and these data were subsequently collected by the hospital. RESULTS: The study included 307 trauma patients with an average age of 51.7 ± 20.9. Based on the ISS (injury severity score), severe trauma was diagnosed in 50 (16.3%) patients. MGAP had the best sensitivity/specificity ratio when the obtained values indicated severe trauma. The sensitivity and specificity were 93.4 and 62.0%, respectively, for an MGAP value of 22. MGAP and GAP were strongly correlated with each other and were statistically significant in predicting the outcome of treatment (OR 2.23; 95% Cl 1.06-4.70; p = 0.035). With a rise of one in the MGAP score value, the probability of survival increases 2.2 times. CONCLUSION: MGAP and GAP, in prehospital settings, had higher sensitivity and specificity when identifying patients with a severe trauma and predicting an unfavorable outcome than other scoring systems.

The Effects of Different Doses of Sildenafil on Coronary Blood Flow and Oxidative Stress in Isolated Rat Hearts.

The dose-response relationship of sildenafil effects on cardiac function is not completely elucidated. The aim of this study was to assess the effects of different doses of sildenafil on coronary flow and oxidative stress in isolated rat hearts. Coronary flow and markers of oxidative stress, including nitrite outflow, and superoxide anion production in coronary effluent, were determined for isolated rat hearts. The experiments were performed during control conditions and in the presence of sildenafil (10, 20, 50, 200 nM) alone or with Nω-nitro-L-arginine monomethyl ester (L-NAME) (30 µM). Sildenafil was shown to result in a significant increase in coronary flow at lower coronary perfusion pressure (CPP) values at all administered doses, whereas, with an increase in CPP, a reduction in coronary flow was observed. An increase in nitric oxide (NO) was most pronounced in the group treated with the lowest dose of sildenafil at the highest CPP value. After the inhibition of the NO-cyclic guanosine monophosphate (cGMP) signaling (NOS) system by L-NAME, only a dose of 200 nM sildenafil was high enough to overcome the inhibition and to boost release of O2-. That effect was CPP-dependent, with statistical significance reached at 80, 100 and 120 mmHg. Our findings indicate that sildenafil causes changes in heart vasculature in a dose-dependent manner, with a shift from a vasodilatation effect to vasoconstriction with a pressure increase. The highest dose administered is capable of producing superoxide anion radicals in terms of NOS system inhibition.

Tadalafil in Increasing Doses: The Influence on Coronary Blood Flow and Oxidative Stress in Isolated Rat Hearts.

INTRODUCTION: This study aimed to assess the influence of different doses of tadalafil on coronary flow and oxidative stress in isolated rat hearts. METHODS: The hearts of male Wistar albino rats (n = 48) were retrogradely perfused according to the Langendorff technique at gradually increased constant perfusion pressure (CPP) (40-120 mm Hg). Coronary flow and oxidative stress markers: nitrite oxide (NO) outflow and superoxide anion production in coronary effluent were measured. The experiments were performed during control conditions and in the presence of tadalafil (10, 20, 50, and 200 nM) alone or with Nω-nitro-L-arginine monomethyl ester (L-NAME) (30 µM). RESULTS: Tadalafil administration significantly increased coronary flow at all CPP values at all administered doses. Tadalafil led to an increase in the NO levels, but a statistically significant NO release increase was found only at the highest dose and highest CPP. Tadalafil did not significantly affect the release of O2-. After inhibiting the nitrite oxide synthase system by L-NAME, tadalafil-induced changes in cardiac flow and NO levels were reversed. L-NAME administration had no pronounced effect on the O2- release. CONCLUSION: Tadalafil causes changes in the heart vasculature in a dose-dependent manner. It does not lead to a significant increase in the production of superoxide anion radicals.

The prevalence of low back pain among nurses in Serbia.

BACKGROUND: The presence of low back pain in nurses is becoming increasingly prominent and it has significant impact both on the individual as well as on the community. OBJECTIVE: The aim of this study was to determine the prevalence of low back pain among practicing nurses. METHODS: The research has been conducted in five health care institutions in the area of Vojvodina. Data were collected using the Nordic Musculoskeletal Questionnaire (NMQ). RESULTS: Five hundred and twelve nurses participated in this study. Most of the participants (93.95%) indicated that they experienced discomfort or pain in the lower back in the last 12 months. Due to low back pain, 61.95% of participants had reduced working abilities and 76.09% of participants have never taken time off from work. CONCLUSIONS: Due to low back pain nurses have a reduced working capacity, but they nevertheless rarely seek medical help or the change of the work place. The implementation of better ergonomic approach and adequate organization of work could reduce the occurrence of low back pain.

The effects of aging and driving experience on reaction times of professional drivers.

BACKGROUND: Professional drivers are part of the active working population, so there is a need for continuous improvement of operating efficiency and safety in driving. Reaction time is a very important driver's trait. OBJECTIVE: The aim of this study was to examine the effects of age and driving experience on reaction times of professional drivers. METHODS: This study assesses part of driving efficiency of professional drivers by measuring simple reaction time and complex reaction time which are important to driving safety. Reaction times of 278 male professional drivers were tested using a hardware-software system for determining the speed of response to psychomotor simple and complex audio-visual stimuli. RESULTS: Our results showed a positive correlation between ageing and slowing of reaction times. This suggests that the natural ageing process clearly slows down reaction times. CONCLUSIONS: The response times of professional drivers are more dependent on age than on driving experience.

Environmental Transformation of Pharmaceutical Formulations: A Scientific Review.

Environmental pollution caused by pharmaceuticals and their transformation products (TPs) has become an increasingly important concern, due to the increased use of pharmaceutical formulations exposed to environmental change. Considerable concerns have been raised regarding potential toxic effects of the transformation products of pharmaceutical formulations on human health. Environmental risk assessments are mostly based on one active component, which causes different ecotoxicological effects, albeit the particular component is present in the environment as a part of a multicomponent mixture with different pharmaceuticals and excipients. The purpose of this review was to present the insight and new knowledge recently obtained by studies on the risk of pharmaceutical formulations, including all contained excipients, pharmaceuticals, and their transformation products exposed to the environment. Numerous studies have shown that the level of pharmaceuticals in the environment is below toxic concentration; however, long exposure to very low concentrations can still lead to harmful concentrations in biota. Accordingly, the findings of this study are expected to highlight the existing issues of the effect of pharmaceutical formulations to the environment, including TPs, and help to determine future research directions towards accumulating the data and improving ecological risk assessment.

Bile acids and their oxo derivatives: environmentally safe materials for drug design and delivery.

PURPOSE: Animal tests have been often used in toxicology to determine parameters describing toxicity of a particular substance. However, in vivo tests must fulfill ethical requirements, and are both time and money consuming. Therefore, computational methods are considered to be very useful in toxicity prediction. METHODS: Retention parameters were acquired by normal-phase TLC. Lipophilicity was used as a key parameter for predicting toxic potential. The correlation coefficients between calculated log P values obtained by five different software and experimentally determined hydrophobicity parameters ([Formula: see text](tol/et), [Formula: see text](tol/but), b(tol/et) and b(tol/but)) were calculated. RESULTS: Correlation analysis provided reliable information (r2 > 0,8) for aquatic species - minnow, medaka, daphnia, and algae. In addition valuable data regarding rodents and AMES test were obtained. CONCLUSIONS: Tested bile acids show relatively good toxicological properties. Less toxic effects are noticed in compounds with higher polarity. Compounds 5, 6, 7, 12, and 13 would be the best candidates for further testing. These compounds show good biological potential which is coupled with low toxicity.

The Effect of Diabetes and Hypertension on the Placental Permeation of the Hydrophilic Drug, Ranitidine.

INTRODUCTION: Ranitidine is a hydrophilic weak base and an H2-receptor antagonist which is commonly used for gastroesophageal reflux, including during pregnancy. It has limited placental permeation and can be used as a pre-anesthetic antacid to prevent aspiration of acidic stomach contents. Recent studies suggest that diabetes and hypertension may influence placental permeation of hydrophilic drugs. Thus, this study aimed to investigate the influence of diabetes and hypertension on ranitidine's placental permeation in pregnant women. METHODS: Forty one pregnant women all scheduled for elective cesarean section entered the study: healthy control (n = 15), with hypertension (n = 16) and with gestational diabetes (n = 10). All women received 50 mg of ranitidine intravenously. Three samples of maternal plasma (after ranitidine application, at delivery and after delivery), and two umbilical cord samples (arterial and venous blood) were collected and analyzed for ranitidine concentrations. Maternal pharmacokinetic parameter were calculated as well as feto:maternal and umbilical cord arterial to venous concentration ratios. RESULTS: Ranitidine maternal and umbilical cord (arterial and venous) concentrations were similar in all three groups and there were no difference between feto:maternal ratios nor volume of distribution, clearance and half life between the groups. DISCUSSION: Fetal concentrations are dependent on maternal concentrations in healthy and hypertensive women but not in diabetic women. Hypertension and diabetes did not affect fetal handling of ranitidine. Though hypertension and diabetes did not influence ranitidine placental permeation, it appears they altered time needed to achieve unity between maternal and fetal plasma.

Location of out-of-hospital cardiac arrest as a determinant in the survival of patients.

Introduction: Cardiac arrest (CA) is defined as a sudden cessation of normal circulation of blood due to failure of the heart to contract effectively during systole. Objective: The aim of this study was to determine the difference in outcome among patients, depending on the location of out-of-hospital CA; to determine the influence of observed determinants on the survival rate. Methods: Observational and retrospective study was conducted in the Institute for Emergency Medical Service Novi Sad (IEMS NS). It included patients who underwent cardiopulmonary resuscitation (CPR) by medical ambulance squads. Patients were divided into three groups, based on the location of CA: private place, public place, and medical institution. Results: CA occurred in private places in 151 cases (76.26%). The shortest duration of a phone call with the dispatcher and Reaction Time I was in the group of patients with CA in a public place (59.1 ± 36.4 seconds and 137.1 ± 89.8 seconds, respectively). CA was recognized in more than 80% of cases, but CPR was initiated in only 9.09% of patients in private places and in 19.35% of patients in public places. Though they initially presented with shockable rhythm in 57.14% of cases in public places, this group has the worst immediate outcome (11.43%), in contrast to the patients with CA in medical institutions (58.33%). Factors determining the survival of patients with CA were CPR attempted immediately after collapse, initial rhythm and eyewitnesses of CA. Conclusion: In order to improve survival of patients with out-of-hospital CA, both education of laymen and introduction of standard questioning protocol in the IEMS Call Centre are necessary.

Influence of bile acid derivates on morphine analgesic effect in mice.

BACKGROUND/AIM: It is known that bile acids improve the absorption, bioavailability and pharmacodynamic characteristics of some drugs. Morphine analgesia is produced by activation of opioid receptors within the central nervous system (CNS) at both spinal and supraspinal levels. Since a morphine molecule contains 3 polar groups and therefore hard to transfer through the blood-brain barrier, the aim of the study was to examine the potential influence of bile acids derivates, namely sodium salt of monoketocholic acid (MKH-Na) and methyl ester of monoketocholic acid (MKH-Me), on analgesic effect of morphine. METHODS: White male mice of NMRI-Haan strain, with body weight of 20-24 g, were used in this study. The analgesic effect of morphine (administered by subcutaneous and intramuscular route in a dose of 2 mg/kg), with and without pretreatment with MKH-Na (4 mg/kg) and MKH-Me (4 mg/kg) was estimated by the hot plate method. RESULTS: Administration of MKH-Me prior to subcutaneous administration of morphine increased the morphine analgesic effect but the increase was not statistically significant. At the same time administration of MKH-Na did not affect morphine analgesic effect. The analgesic effect of morphine increased when administered intramuscularly 20 min after MKH-Me administration. When compared with the group of animals treated only with morphine, a statistically significant increase in analgesic effect was detected 10, 30, 40 and 50 min after morphine administration (p < 0.05). Pretreatment with MKH-Na did not affect morphine analgesic effect. CONCLUSION: According to the results of this study it can be presumed that after intramuscular morphine administration methyl ester of monoketocholic acid increases morphine transport into the central nervous system and consequently the analgesic effect, as well. Further research on bile acids-morphine interaction both in vitro and in vivo is necessary to completely elucidate the mechanism of this interaction and increase in the morphine analgesic effect.

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.

Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat.

Major problem for diabetic patients represents damage of blood vessels and the oxidative stress of the brain cells due to increased concentration of free radicals and poor nutrition of brain cells. Gliclazide has antioxidative properties and poor blood brain barrier (BBB) penetration. Bile acids are known for their hypoglycemic effect and as promoters of drug penetration across biological membranes. Accordingly, the aim of this study is to investigate whether the bile acid (deoxycholic acid) can change the permeation of gliclazide, through the blood brain barrier of a rat model type-1 diabetes. Twenty-four male Wistar rats were randomly allocated to four groups, of which, two were given alloxan intraperitoneally (100 mg/kg) to induce diabetes. One diabetic group and one healthy group were given a bolus gliclazide intra-arterially (20 mg/kg), while the other two groups apart from gliclazide got deoxycholic acid (4 mg/kg) subcutaneously. Blood samples were collected 30, 60, 150, and 240 seconds after dose, brain tissues were immediately excised and blood glucose and gliclazide concentrations were measured. Penetration of gliclazide in groups without deoxycholic acid pretreatment was increased in diabetic animals compared to healthy animals. Also in both, the healthy and diabetic animals, deoxycholic acid increased the permeation of gliclazide through that in BBB.

Effect of fullerenol C(60)(OH) (24) on lipid peroxidation of kidneys, testes and lungs in rats treated with doxorubicine.

The aim of this study is to investigate the protective effect of fullerenol C60(OH)24 in various doses, on lipid peroxidation of rat's kidneys, testes and lungs after application of doxorubicin. The experiment was performed on healthy male Wistar rats. The animals were randomly divided into five experimental groups and treated with saline (0.9 % NaCl i.v.), doxorubicin alone (10 mg/kg i.v.), combination of doxorubicin/fullerenol (50 and 100 mg/kg fullerenol, respectively, 30 min before the introduction of doxorubicin) and fullerenol alone (100 mg/kg), respectively. Animals were killed on the 2nd and 14th day after treatment. Products of lipid peroxidation and thiobarbituric acid are determined spectrophotometrically from the crude homogenate fraction of the kidney, testis and lung tissues of the rats. Fullerenol, applied as a pre-treatment of doxorubicin, significantly reduced or completely prevented the appearance of doxorubicin toxicity in kidneys and testes, in both tested doses. A dose of 100 mg/kg i.p. exhibited a better protective effect. When fullerenol was applied alone, at a dose of 100 mg/kg i.p, it did not significantly affect the intensity of lipid peroxidation in all tested organs.

Effect of simultaneous exposure to benzene and ethanol on urinary thioether excretion.

The toxicity of benzene is not an issue of the past, especially in developing countries. Bone marrow toxicity is demonstrated among workers. In this study, the effect of simultaneous exposure to benzene and ethanol on benzene metabolism in mice was investigated by measuring the excretion of thioethers in urine. Urinary thioether excretion significantly decreased in the mice receiving both benzene and ethanol compared with the animals receiving benzene only. The assay of determining thioethers in urine samples in this study is a simple and low-cost method, thus suitable for routine use, especially in developing countries, not only for benzene, but also for other alkilating agents, which can be found during occupational exposure. Our results suggest that further research is needed to elucidate the mechanisms of decreased urinary excretion of thioether after simultaneous exposure to benzene and ethanol.

[Effect of chromium enriched fermentation product of barley and brewer's yeast and its combination with rosiglitazone on experimentally induced hyperglycaemia in mice].

INTRODUCTION: In the recent years, herbal preparations have been more used to treat diabetes. Dietetic supplement based on barley and beer yeast enriched with chromium (BBCr) is registered in Serbia as a supplement in the treatment of type 2 diabetes. OBJECTIVE: To investigate the effect of the preparation based on barley and brewer's yeast with chromium (BBCr), rosiglitazone (R) and their combination (BBCr+R) on fasting glycaemia and glycaemia in mice after glucose, adrenalin and alloxan application. METHODS: The animals were divided into three groups: glucose 500 mg/kg (I); adrenalin 0.2 mg/kg (II); and alloxan 100 mg/kg (III) and into subgroups according to the substance they received (BBCr: 750 mg/kg, R: 0.75 mg/kg and BBCr+R). Each animal was its own control in respect of glycaemia before and after the treatment with test substances, except for group III which contained a placebo subgroup. RESULTS: BBCr caused a significant decrease of fasting glycaemia and significant reduction of glycaemia after glucose load compared to the values before treatment (7.4 +/- 0.6 mmol/l vs 9.2 +/- 0.6 mmol/l; p=0.01). R and BBCr+R significantly decreased glycaemia after adrenalin load (R: 8.6 +/- 1.8 mmol/l vs 15.4 +/- 3.2 mmol/l; p=0.004; BBCr+R: 9.6 +/- 2.4 mmol/l vs 15.0 +/- 4.4 mmol/l; p=0.04). After alloxan application the glycaemia was significantly lower in the subgroups treated with BBCr, R and BBCr+R compared to placebo subgroup (10.1 +/- 8.0 mmol/l vs 6.8 +/- 2.7 mmol/l vs 13.5 +/- 9.7 mmol/l vs 24.5 +/- 4.7 mmol/l; p=0.001). CONCLUSION: Pretreatment with BBCr caused a significant reduction of fasting glycaemia and glycaemia after glucose load. Rosiglitazone and BBCr+R caused a significant reduction of glycaemia after adrenalin load. Pretreatment with BBCr, R and BBCr+R prevented the onset of experimental diabetes caused by alloxan, which was confirmed by histological analysis of pancreas tissue.

The protective effects of silymarin against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats.

Silymarin is a complex of five major compounds, and silibinin is the most biologically active component of the complex. The aim of this study was to investigate, evaluate and confirm the potential cardioprotective and hepatoprotective effects of administration of silymarin, rich in silibinin, at a dose of 60 mg/kg orally for a time-span of 12 days on doxorubicin induced toxicity in male Wistar rats. The in vivo model was used to explore whether silymarin could prevent damage of liver and heart tissue induced by doxorubicin administered every other day at dose of 1.66 mg/kg intraperitoneally for twelve days. In the study the change of body weight, ECG changes, biochemical parameters of oxidative stress, serum activity of alanine and aspartate transaminase, lactate dehydrogenase, creatine kinase and histological preparations of heart and liver samples of treated animals were examined. According to physiological, pharmacological, microscopic and biochemical results, we confirmed that at the examined dose, silymarin exhibits a protective influence on the heart and liver tissue against toxicity induced by doxorubicin.

Hypoglycaemic action of stevioside and а barley and brewer's yeast based preparation in the experimental model on mice.

The aim of this study was to investigate influence of the preparation based on barley and brewer's yeast extracts with chromium (BBCr) and stevioside (S) on fasting glycaemia and glycaemia in mice after glucose, adrenalin and alloxan application. The animals were divided into three groups: glucose 500 mgkg(-1) (I); adrenalin 0.2 mgkg(-1)(II) and alloxan 100 mg kg(-1) (III) and into subgroups according to the substance they received: stevioside 20 mg kg(-1) (I-S, II-S, III-S); BBCr 750 mg kg(-1)(I-BBCr, II-BBCr, III-BBCr) and saline 1 ml/100g (III-placebo). Glycaemia was measured before and after 7-day treatment with stevioside or BBCr in the following conditions: fasting, 30 min after glucose load (I) or 45 min after adrenaline load (II). In group III glycaemia was measured before and after 12-day treatment with S, BBCr or placebo and alloxan application (7th, 8th and 10th days of treatment ). BBCr significantly reduced fasting glycaemia in I and II groups and glycaemia values after the glucose load (I-BBCr: 9.20 ± 0.61 vs. 7.42 ± 0.59 mmol/L, p = 0.01). Stevioside significantly reduced glycaemia after the adrenalin load (II-S: 13.45 ± 0.71 vs. 11.65 ± 1.19 mmol/L; p = 0.03). In the III-BBCr glycaemia values did not indicate the development of alloxan-induced diabetes and were significantly lower than in the III-placebo (8.6 ± 3.16 vs. 18.8 ± 5.53 mmol/L; p < 0.05). In conclusion, BBCr caused a significant decrease of fasting glycaemia, significant reduction of glycaemia after glucose load and prevented onset of alloxan-induced diabetes. Stevioside caused the decrease of adrenalin-induced hyperglycaemia.

Antioxidant properties of fullerenol C60(OH)24 in rat kidneys, testes, and lungs treated with doxorubicin.

Clinical use of doxorubicin continues to be challenged by its undesirable systematic toxicity, caused mainly by oxidative stress. The aim of this study was to investigate the effectiveness of fullerenol C(60)(OH)(24) polyanion nanoparticles, an antioxidant agent, against doxorubicin-induced nephro-, testicular, and pulmonary toxicity. Results obtained in vitro suggest that fullerenol's anti-proliferative property and protective effect against doxorubicin cytotoxicity are mediated by the antioxidative and radical scavenging activity. Male Wistar rats were divided into five treatment groups: the control group (I) received 0.9% NaCl (1 mL/kg, i.p.). Groups II, III, IV, and V received a single dose of doxorubicin (10 mg/kg i.p.), doxorubicin/fullerenol (100 and 50 mg/kg i.p. of fullerenol 30 min prior to 10 mg/kg i.p. of doxorubicin), and fullerenol (100 mg/kg i.p.), respectively. On the 2(nd) and 14(th) days, organ samples were taken for the measurement of lipid peroxidation and activities of superoxide dismutase, catalase, glutathione-peroxidase, -reductase, and -transferase. Doxorubicin induced a significant increase of lipid peroxidation and alterations of antioxidant enzyme activities, while the fullerenol pre-treatment prevented the effects of doxorubicin on investigated parameters. Fullerenol, applied alone, did not alter basal values of the investigated animals. Considering the mechanisms of doxorubicin toxicity, it can be concluded that fullerenol exerts its protective role by acting as a free radical sponge and/or by removing free iron through formation of fullerenol-iron complex. Results of this study support the hypothesis of testicular, pulmo-, and nephroprotective efficacy of fullerenol in preventing oxidative stress induced by doxorubicin.

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

This 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 (OGTTT) 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.