Hanefi Özbek

Hepatoprotective effect of Foeniculum vulgare essential oil

Hepatoprotective activity of Foeniculum vulgare (fennel) essential oil (FEO) was studied using carbon tetrachloride (CCl(4)) induced liver injury model in rats. The hepatotoxicity produced by acute CCl(4) administration was found to be inhibited by FEO with evidence of decreased levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin. The results of this study indicate that FEO has a potent hepatoprotective action against CCl(4)-induced hepatic damage in rats.

CISPLATIN INDUCES ACUTE RENAL FAILURE BY IMPAIRING ANTIOXIDANT SYSTEM IN GUINEA PIGS: EFFECTS OF ANTIOXIDANT SUPPLEMENTATION ON THE CISPLATIN NEPHROTOXICITY

This study aims to investigate the role of oxidants in cisplatin-induced nephrotoxicity. Cisplatin was administered intraperitoneally (i.p.) in a single dose (5 mg/kg) and guinea pigs were killed either after 24 h or 7 days. The same experiment was performed using animals treated with vitamins C and E combination and a natural antioxidant extract (SARMEX®). The kidneys were then removed to be used in the analyses. Blood samples were also obtained from the animals to be used in routine biochemical assays. Twenty-four hours after treatment there was a significant decrease in the renal activities of total superoxide scavenger activity (TSSA), superoxide dismutase (SOD) and catalase (CAT) accompanied by a rise in malondialdehyde (MDA) levels. After 7 days, the fall in kidney enzymatic activities was far greater, while the increase in blood urea (BUN) and creatinine (CRE) was marked. Treatment with antioxidants causes significant increases in renal TSSA (7 day), non-enzymatic superoxide scavenger activity (NSSA) (24 h and 7 day) and SOD (7 day) activities, does not change glutathione peroxidase (GSH-Px) activity and decreases renal MDA (24 h and 7 day), blood BUN (7 day) and CRE (7 day) levels. Our results suggest that cisplatin treatment impairs both enzymatic and non-enzymatic antioxidant systems and causes peroxidation in the renal tissue, which leads to kidney failure. Antioxidant supplementation strengthens the renal antioxidant system, eliminates oxidation reactions, and prevents cisplatin-induced kidney failure.

Anti-fibrogenic effects of captopril and candesartan cilexetil on the hepatic fibrosis development in rat: The effect of AT1-R blocker on the hepatic fibrosis

BACKGROUND/AIM Angiotensin converting enzyme (ACE) and angiotensin II (AT-II) have been suggested to play an important role in liver fibrogenesis. There is a significant relationship between inheritance of hightened expression of transforming growth factor beta1 (TGF-beta1) and AT-II and the development of progressive hepatic fibrosis. The purpose of this study was to investigate the effects of captopril, an ACE inhibitor and candesartan cilexetil, an AT-II type 1 receptor (AT1-R) blocker, on liver fibrosis induced in rats by carbon tetrachloride (CCl4) administration. METHODS rats were divided into 4 experimental groups: The first group was given CCl4 alone; the second was given both CCl4 and captopril (100 mg x kg(-1) x day(-1)); the third was given both CCl4 and candesartan cilexetil (8 mg x kg(-1) x day(-1)); fourth group was given 0.9% NaCl only. Seven weeks after initiating the treatment, indices of fibrosis were assessed. RESULTS Candesartan cilexetil treatment significantly reduced the fibrosis development. These inhibitory effects were not observed in the captopril-treated group. The mean fibrosis score was significantly lower in the CCl4/candesartan group compared with the group applied to CCl4 alone and the group applied to CCl4/captopril. Similarly, the number of alpha-smooth muscle actin positive cells was markedly suppressed by candesartan treatment. CONCLUSIONS The results suggest that AT-II plays a pivotal role in hepatic fibrogenesis and candesartan significantly attenuates the progression of liver fibrosis. This drug may provide an effective new strategy for prevention of liver fibrosis. Its effectiveness should be investigated in chronic liver disease associated with progressive fibrosis.

Evaluation of analgesic, anti-inflammatory and hepatoprotective effects of lycorine from Sternbergia fisheriana (Herbert) Rupr.

The present study reports the potential antinociceptive, anti-inflammatory and hepatoprotective activities of lycorine from Sternbergia fischeriana (Herbert) Rupr. (Amaryllidaceae). Lycorine was evaluated on mice by using acetic-acid induced writhing and tail-flick tests. Lycorine exhibited stronger inhibition than aspirin in acetic-acid induced abdominal stretching at 1.0mg/kg dose. Lycorine also showed antinociceptive activity at 1.0mg/kg dose in tail-flick test. The anti-inflammatory activity of lycorine was not found to be significant at dose of 0.5mg/kg. However, at doses of 1.0mg/kg and 1.5mg/kg, i.p. showed a significant reduction with 53.45% and 36.42%, respectively in rat paw oedema induced by carrageenan against the reference anti-inflammatory drug indomethacin (3mg/kg, i.p.) (95.70%). The ED(50) of lycorine was determined as 0.514 mg/kg. Hepatoprotective activity of lycorine on carbon tetrachloride (CCl(4)) induced acute liver toxicity following biochemical parameters were also evaluated. Rats were treated with lycorine at doses of 1.0mg/kg and 2.0mg/kg, i.p. Results of biochemical tests were confirmed by histopathological examination. Lycorine exhibited significant hepatoprotective effect at dose of 2.0mg/kg i.p. dose.

Hepatoprotective and anti-inflammatory activities of Plantago major L.

Objective: The aim of this study was to investigate anti-inflammatory and hepatoprotective activities of Plantago major L. (PM). Materials and Methods: Anti-inflammatory activity: Control and reference groups were administered isotonic saline solution (ISS) and indomethacin, respectively. Plantago major groups were injected PM in doses of 5 mg/kg (PM-I), 10 mg/kg (PM-II), 20 mg/kg (PM-III) and 25 mg/kg (PM-IV). Before and three hours after the injections, the volume of right hind-paw of rats was measured using a plethysmometer. Hepatoprotective Activity: The hepatotoxicity was induced by carbon tetrachloride (CCl4) administration. Control, CCl4 and reference groups received isotonic saline solution, CCl4 and silibinin, respectively. Plantago major groups received CCl4 (0.8 ml/kg) and PM in doses of 10, 20 and 25 mg/kg, respectively for seven days. Blood samples and liver were collected on the 8th day after the animals were killed. Results: Plantago major had an anti-inflammatory effect matching to that of control group at doses of 20 and 25 mg/kg. It was found that reduction in the inflammation was 90.01% with indomethacin, 3.10% with PM-I, 41.56% with PM-II, 45.87% with PM-III and 49.76% with PM-IV. Median effective dose (ED50) value of PM was found to be 7.507 mg/kg. Plantago major (25 mg/kg) significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels when compared to the CCl4 group. The histopathological findings showed a significant difference between the PM (25 mg/kg) and CCl4 groups. Conclusion: The results showed that PM had a considerable anti-inflammatory and hepatoprotective activities.

Effects of hyaluronic acid on postoperative adhesion of tendo calcaneus surgery: an experimental study in rats.

Adhesions are a significant problem after tendon surgery. The effects of hyaluronic acid on adhesion formation of the tendo calcaneus were investigated in this study. Twenty Wistar rats were utilized. Both tendo calcanei were incised transversely, and then repaired. Hyaluronic acid (0.2 cc) was injected into peritendinous tissue on the right side, while the same amount of normal saline was injected to the left side as a control. The animals were sacrificed 40days after the experiment. Both the right and left tendon adhesions were evaluated both macroscopically and microscopically for the presence of adhesions (grading scale 0-4). Throughout the experimental period, there was no difference in range of motion of the ankle between the two groups. Macroscopically, there were fewer adhesions in the experimental group (mean 0.6 +/- 0.8) compared to the controls (mean 1.1 +/- 0.2). This difference was not statistically significant (p = .096). Histopathologically, these parameters were similar in both the experimental (mean 1.15 +/- 0.98) and the control groups (mean 1.9 +/- 1.25). This difference was significant (p = .043). Hyaluronic acid may be effective for prevention of adhesions in the tendo calcaneus though this effect could not be demonstrated experimentally.

Acute amitriptyline intoxication: an analysis of 44 children.

The tricyclic antidepressant agents, particularly amitriptyline and dothiepin, are recognized for their potentially lethal cardiovascular and neurological effects in poisoned patients. In this article, the clinical and laboratory findings of 44 children with amitriptyline intoxication are reviewed. Our purpose was to investigate amitriptyline intoxication in childhood. Of 44 patients, 21 (47.7%) were boys, 23 (52.3%) were girls, and the ages ranged from 12 months to 14 years (mean9 / SD; 4.099 / 2.9 years). All children except one who took an overdose of amitriptyline to decrease his pain accidentally ingested an overdose of amitriptyline. The amount of amitriptyline ingested was between 2 mg/kg and 97.5 mg/kg (mean9 / SD; 13.69 / 17.7 mg/kg per dose) (the drug dosage was not known in 13 children). The most commonly observed clinical and laboratory findings were lethargy, tachycardia, convulsion, hyperglycemia and leukocytosis. In all patients except for two children who died the abnormal clinical and laboratory findings returned to normal within a few days after admission and they were discharged from the hospital in good health within the fourth day of admission. One of the children ingested 97.5 mg/kg amitriptyline and probably died due to status epilepticus and another child who died ingested 36 mg/ kg amitriptyline and died due to cardiopulmonary arrest. In conclusion, our findings showed that initial symptoms and signs of acute amitriptyline intoxication appeared severe, but they disappeared with only supportive care required in most children except for cases that ingested high doses of drug within a few days. In contrast to adults, we infrequently noted respiratory insufficiency, arrhythmia and hypotension in children with acute amitriptyline intoxication.

Aspirin impairs antioxidant system and causes peroxidation in human erythrocytes and guinea pig myocardial tissue

This study aims to investigate possible effects of aspirin treatment on cellular oxidant/antioxidant system. In the first part of the study, 15 guinea pigs were given aspirin at three different doses (2200, 440 and 10 mg/kg/day) for 30 days and five were fed on the same diet without aspirin. After a month, animals were killed and their hearts were removed for use in analyses. In the other part, after fasting blood samples were obtained from 11 volunteer subjects, they were given aspirin (approximately 10 mg/kg/day) for 30 days and second blood samples were obtained after 1 month. Five volunteer subjects also participated as placebo control. Oxidant/antioxidant parameters, namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), nonenzymatic superoxide scavenger activity (NSSA), susceptibility to oxidation (SO) and antioxidant potential (AOP) values, were assayed in the samples. Antioxidant system was found to be impaired in the heart tissue from guinea pigs and in the erythrocytes from volunteer subjects. AOP and NSSA values were lower and MDA higher after aspirin treatment in both heart tissues and erythrocytes. In guinea pig heart tissue, SO was lower, but GSH-Px and CAT were unchanged after aspirin treatment. In human erythrocytes, SO was unchanged, but GSH-Px and CAT activities were increased after aspirin treatment. Changes in guinea pig heart tissues from animals treated with higher aspirin doses were more drastic relative to those of human erythrocytes, but no meaningful differences were observed between analysis parameters of control and lower-dose (10 mg/kg/day) aspirin-treated animals. Our results suggest that high-dose aspirin exerts significant toxicity to guinea pig myocardium and normal dose aspirin may cause peroxidation in the human erythrocytes due to its oxidant potential. We suppose that antioxidant supplementation may be beneficial for the people using aspirin for longer periods in order to prevent peroxidation damages.

Antinociceptive and anti-inflammatory activities of Viburnum opulus

Water extract of Viburnum opulus L. (Caprifoliaceae) (VO) leaf was investigated for antinociceptive and anti-inflammatory activities in mice and rats. The tail flick test, acetic acid-induced writhing test, and the carrageenan-induced rat paw edema test were used to determine these effects. Our findings show that VO causes dose related inhibition in acetic acid-induced abdominal stretching in mice. VO inhibited abdominal stretching at 100 and 200 mg/kg. VO showed antinociceptive activity, which was quantified by the tail-flick test at doses of 100 and 200 mg/kg. However, VO did not have an anti-inflammatory effect at these doses. The LD50 of VO was determined as 5.447 g/kg.

Analgesic compounds from Scorzonera latifolia (Fisch. and Mey.) DC.

ETHNOPHARMACOLOGICAL RELEVANCE A traditional mastic named yaki sakizi prepared from the roots of Scorzonera latifolia (Fisch. and Mey.) DC. is used as a folk remedy for treatment of pain in Turkish folk medicine. AIM OF THE STUDY To isolate and identify the compounds responsible for the antinociceptive activity of S. latifolia using bioassay-guided fractionation. MATERIALS AND METHODS The methanolic extract of the S. latifolia roots was prepared and subjected to isolation procedures such as solvent-solvent partitioning and column chromatography. Writhing and tail-flick tests were used to determine the antinociceptive activity. RESULTS The n-hexane fraction of the S. latifolia root methanolic extract showed potent antinociceptive activity in both writhing and tail-flick tests. Three compounds were isolated from n-hexane fraction using bioassay-guided chromatographic purification. Isolated compounds were the triterpene taraxasteryl myristate, taraxasteryl acetate, and fern-7-en-3-beta-one, structures were elucidated by means of MS and NMR techniques. Both taraxasterol derivatives showed promising antinociceptive activity when compared to reference compounds. CONCLUSION Results of the present study support the usage of S. latifolia in Turkish folk medicine. Both plant root extract and the isolated compounds showed promising antinociceptive activities. Our results suggested that antinociceptive activity of the plant extract is probably caused by the synergistic interaction of the isolated compounds.