Hypocholesterolemic effect of khellin and khelloside in female cynomolgus monkeys

Khellin and khelloside (khellol glucoside) were examined in female cynomolgus monkeys to substantiate their ability to favorably modify serum lipoprotein cholesterol. Clinical chemistry parameters were also measured to obtain information indicative of possible drug toxicity. Both drugs were evaluated in two week multiple-dose studies and after a single oral dose. After two weeks at 20 mg/kg per day, khellin and khelloside significantly lowered low density lipoprotein cholesterol (LDL-C) by 87% and 73%, high density lipoprotein cholesterol (HDL-C) by 41% and 23%, and total-C by 55% and 44%, respectively. Very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG) were not changed. No apparent toxicity was observed as clinical chemistry parameters and body weights were not different compared to control values. Similar results were observed with lower doses of khellin and khelloside. Khellin at 5 mg/kg per day reduced LDL-C by 50%, HDL-C by 15%, and total-C by 30%, while khellol glucoside at 10 mg/kg per day lowered LDL-C by 46%, HDL-C by 20%, and total-C by 31%. Neither drug produced significant changes in VLDL-C, TG, body weights, or clinical chemistry variables. A 2 mg/kg per day dose of khellin also had no observable effect in this study. Single oral doses (20 mg/kg) of khellin and khelloside caused modulation of LDL-C (-32% and -30%) and total-C (-18% and -15%). Visual observation of the monkeys during this study revealed that khellin caused emesis in 9/9 animals, while khelloside and control had no emetic effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypolipidaemic effect of Casearia esculenta root extracts in streptozotocin-induced diabetic rats

The hypolipidaemic effect of an aqueous extract of Casearia esculenta root, an indigenous antidiabetic medicine popularly used in rural South India was investigated. Administration of the extract of C. esculenta (200 and 300 mg/kg body wt.) for 45 days resulted in significant reduction in serum and tissue cholesterol, phospholipids, free fatty acids and triglycerides in streptozotocin (STZ) diabetic rats. In addition to that, significant (p < 0.05) decrease in high density lipoprotein (HDL) whereas significant increase (p < 0.05) in low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were observed in STZ diabetic rats, which was normalized after 45 days of C. esculenta root extract treatment. The root extract at dose of 300 mg/kg body wt. showed much significant hypolipidaemic effects than the dose of 200 mg/kg body weight.     

Effects of bezafibrate and gemfibrozil on serum lipoproteins in primary hypercholesterolemia

29 patients with primary hypercholesterolemia were treated for 8 weeks each with either bezafibrate (200 mg t.i.d.) or gemfibrozil (600 mg b.i.d.) in a randomized cross-over trial. Compared to placebo bezafibrate was significantly more effective on low density lipoprotein (LDL)-cholesterol (-28% versus -18%) and the LDL/high density lipoprotein (HDL) ratio (-34% versus -24%) by exploratory statistics. There was also a trend for a more marked reduction of bezafibrate on total cholesterol and apoliproprotein B as well as more pronounced increase in HDL-cholesterol and apolipoprotein A-I. The triglyceride reduction tended to be more extensive with gemfibrozil. Complicance to both drugs was good. No side-effects were observed. The results are considered important with respect to the potential of bezafibrate in reducing the risk of cardiovascular disease.     

Studies on the toxicological profile of the local anaesthetic articaine

The toxicity of articaine (CAS 23964-58-1) and of a respective preparation (Septanest SP; 4% articaine HCl and epinephrine 1: 100,000) was examined in in vitro and in vivo experiments. The following endpoints were examined: repeated dose toxicity, reproduction toxicity, mutagenic potential and local tolerance. Repeated s.c. administration of articaine HCl in rats and dogs demonstrated no pathomorphological systemic changes even at systemically toxic doses. The no-effect level (NOEL) was 25 mg articaine HCl/kg b.w./day s.c. for the rat and 40 mg articaine HCl/kg b.w./day s.c. for the dog. Reproduction studies were performed in rats and rabbits at doses up to more than 10 times the maximum recommended human dose of 7 mg articaine HCl/kg b.w. and revealed no evidence of harm to the foetus or to other aspects of reproduction, even at doses toxic to the parental animals. Four standard in vitro and in vivo mutagenicity studies have shown no mutagenic potential up to cytotoxic concentrations or up to the maximum tolerated dose level. The local tolerance of articaine HCl was good to very good. The preclinical data indicate that articaine HCl does not possess any relevant side-effects or gross toxicity and can be considered a safe local anaesthetic.     

Sodium arsenite-induced cardiotoxicity in rats: protective role of p-coumaric acid,a common dietary polyphenol

Abstract

This study was performed to investigate the ameliorative role of p-coumaric acid against sodium arsenite-induced cardiotoxicity in rats. Sodium arsenite (5?mg/kg/b.wt) was orally administered once a day for 30 days to the animals to induce cardiotoxicity. After the experimental period, cardiotoxicity was assessed by estimating the levels of lipid peroxidation, anti-oxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, total reduced glutathione, protein sulfyhydryl and non-protein sulfhydryl groups) and DNA fragmentation in the cardiac tissue of control and experimental rats. In addition, cardiac tissue specific serum markers (triacylglycerides, total cholesterol, low-density lipoprotein cholesterol and high density lipoprotein cholesterol) in serum and histopathological changes in the cardiac tissue were also evaluated. From the results obtained in our study, sodium arsenite administration to the rats increased lipid peroxidation, DNA fragmentation, triacylglycerides, total cholesterol and low-density lipoprotein cholesterol, whereas antioxidant status and high-density lipoprotein cholesterol were found to be reduced. However, p-coumaric acid (75 and100?mg/kg/b.wt) treatment orally once per day for 30 days, immediately before a daily administration of sodium arsenite protected the abnormal biochemical abnormalities observed in the cardiac tissue of sodium arsenite treated rats as evidenced by the cardiac histopathology. For comparison purpose, a standard antioxidant vitamin C (100?mg/kg/b.wt) was used. In conclusion, this study concluded that p-coumaric acid could be a promising candidate for protecting the sodium arsenite-induced cardiotoxicity in rats through its antioxidant character.     

Acute and subchronic toxicity studies of the new quinolone antibacterial agent irloxacin in rodents.

Irloxacin (6-fluorine-7-(pyrrol-1-yl)-1-ethyl-1, 4-dihydro-4-oxo-quinolone-3-carboxylic acid, CAS 91524-15-1), a new quinolone antibacterial agent, was administered as a single dose to rats and mice both by oral and intraperitoneal route in oder to study its acute toxicity. Its oral subchronic toxicity was also assessed by treating rats for 4 and 13 weeks. The results obtained showed that irloxacin was well tolerated after single administration in mice and rats, with LD50 values above 2000 and 5000 mg/kg for intraperitoneal and oral administration, respectively. In the oral subchronic toxicity studies, the histopathological examination performed after the 13-week treatment period confirmed the kidney as the target organ for toxicity. Increased presence of lipofuscin in the kidneys was observed in animals receiving 2000 or 450 mg/kg/d, and degeneration and/or dilatation of proximal renal tubules and chronic interstitial nephritis in males receiving these dosages. No histopathological findings were observed in the kidneys of animals receiving 100 mg/kg/d for 13 weeks. Other relevant findings were, presence of dark or cloudy urine with slightly lower pH in animals receiving dosages of 450 mg/kg/d and above, increased urinary protein concentration in animals receiving 2000 or 450 mg/kg/d, and increased plasma urea concentration in those receiving 2000 mg/kg/d. Moreover, increased plasma phospholipids and total cholesterol concentration, and increased liver and kidney weights were observed among treated animals. As a summary, the results have shown that irloxacin has a low acute toxicity in both mice and rats. For repeat oral administration in rats, 100 mg/kg can be considered as the non-toxic effect level after a treatment period of 13 weeks.     

Improved lipid profile in ovariectomized rats by red ginseng extract

The effects of red ginseng extract on lipid metabolism were examined in ovariectomized rats. Twenty-four female Sprague-Dawley rats (210 +/- 20 g) were studied for 10 weeks. The rats were divided into four groups: (I) "sham" non-ovariectomized rats treated with olive oil, (II) control ovariectomized rats treated with olive oil, (III) ovariectomized rats treated with 0.5 mg/kg 17beta-estradiol in olive oil, and (IV) ovariectomized rats treated with 5mg/kg red ginseng extract in olive oil. Red ginseng extract induced significant reductions in total cholesterol, low density lipoprotein cholesterol/total cholesterol, high density lipoprotein cholesterol/total cholesterol, and low density lipoprotein cholesterol/high density lipoprotein cholesterol, implying the effectiveness of ginseng in targeting postmenopausal symptoms.     

Effect of bezafibrate and colestyramine in patients with primary hypercholesterolemia

40 patients with primary hypercholesterolemia were included in a randomized cross-over trial comparing effects and tolerance of bezafibrate (Cedur) (200 mg t.i.d.) and colestyramine (4 g t.i.d.). Gastrointestinal side-effects led to the discontinuation of colestyramine in 11 patients. No adverse events were observed with bezafibrate. Both drugs had similar effects on total and low density lipoprotein cholesterol (bezafibrate: -15% and -12%, respectively; colestyramine: -10% and -11%, respectively). While the high density lipoprotein-increasing effect of bezafibrate was more marked (+20% vs. +14%), triglycerides and very low density lipoprotein cholesterol were lowered by bezafibrate (-22% and -27%, respectively) and tended to increase with colestyramine (+11% and +10%, respectively). In the light of results of a multicenter primary prevention trial bezafibrate also should have a protective effect on coronary heart disease. This, however, has to be proven in longterm prospective trials.     

Protective effects of Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) against atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits.

We investigated the protective effects of the traditional Japanese herbal medicine Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang in Chinese) (SRBT) against hypercholesterolemia and atherosclerotic lesions. We focused on atherosclerosis using female heterozygous Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. The total plasma cholesterol levels increased for up to 12 weeks after beginning a diet containing 0.1% cholesterol and then reached a plateau of about 600 mg dl(-1). When SRBT was administered at a dose of 1.0 g kg(-1)per day for 24 weeks, total plasma cholesterol levels were significantly decreased after 20-24 weeks. On the other hand, pravastatin at a dose of 10 mg kg(-1)per day produced a significant decrease in total plasma cholesterol levels from 4 to 24 weeks (about 105-130 mg dl(-1)). Moreover, 1.0 g kg(-1)per day of SRBT significantly decreased plasma low density lipoprotein (LDL) cholesterol levels but did not change either very low density lipoprotein (VLDL), or high density lipoprotein (HDL) cholesterol levels. Animals that received pravastatin had significantly decreased LDL cholesterol levels and VLDL cholesterol levels after 8 weeks and at 24 weeks. We also examined the expression of apoB, E and LDL receptor mRNA levels in the liver at 24 weeks after beginning the administration of 1.0 g kg(-1)per day of SRBT. Both apoE and LDL receptor mRNA levels were significantly increased compared with those in rabbits receiving the 0.1% cholesterol diet. SRBT at a dose of 1.0 g kg(-1)per day significantly depressed the intimal surface area of the thoracic aortae involved with atheromatous plaques. The present results suggest that SRBT may protect against hypercholesterolemia and atheromatous lesions by affecting apoE and LDL receptor mRNA gene expression in the liver.     

Statin-fibrate combination: therapy for hyperlipidemia: a review

Statins and fibrates are well-established treatments for hyperlipidaemias and the prevention of vascular events. However, fibrate + statin therapy has been restricted following early reports of rhabdomyolysis that mainly involved gemfibrozil, originally with bovastatin, and recently, with cerivastatin. Despite this limitation, several reports describing combination therapy have been published. This review considers these studies and the relevant indications and contraindications. Statin + fibrate therapy should be considered if monotherapy or adding other drugs (e.g. cholesterol absorption inhibitors, omega-3 fatty acids ornicotinic acid) did not achieve lipid targets or is impractical. Combination therapy should be hospital-based and reserved for high-risk patients with a mixed hyperlipidaemia characterised by low density lipoprotein cholesterol (LDL) >2.6 mmol/l(100 mg/dl, high density lipoprotein cholesterol (HDL) <1.0 mmol/l (40 mg/dl) and/or triglycerides> 5.6 mmol/l (500 mg/dl. These three 'goals' are individually mentioned in guidelines. Patients should have normal renal, liver and thyroid function tests and should not be receiving therapy with cyclosporine, protease inhibitors or drugs metabolised through cytochrome P450 (especially 3A4). Combination therapy is probably best conducted using drugs with short plasma half-lives; fibrates should be prescribed in the morning and statins at night to minimise peak dose interactions. Both drug classes should be progressively titated from low doses. Regular (3-monthly) monitoring of liver function and creatine kinase is required. In conclusion, fibrate + statin therapy remains an option in high-risk patents. However, long-term studies involving safety monitoring and vascular endpoints are required to demonstrate the efficacy of this regimen.     

PAS疗法对老年血脂紊乱合并颈动脉粥样硬化患者的疗效观察

目的 观察联合应用阿司匹林、阿托伐他汀、普罗布考（PAS疗法）对于老年血脂紊乱患者颈动脉粥样硬化的疗效.方法 选取2011年4月-2012年5月171例血脂紊乱合并颈动脉粥样硬化的老年患者,随机分为PAS组57例、AS组58例、A组56例进行比较研究.PAS组予普罗布考（0.5 g/d）,阿司匹林（100 mg/d）,阿托伐他汀钙（20 mg/d）; AS组予阿司匹林（100 mg/d）,阿托伐他汀钙（20 mg/d）;A组予阿司匹林（100 mg/d）.结果 PAS组、AS组治疗后与本组治疗前及A组治疗后比较,总胆固醇（TC）、甘油三酯、低密度脂蛋白胆固醇（LDL-C）、超敏C反应蛋白、白介素-6、肿瘤坏死因子（TNF）-α水平、颈动脉内膜中层厚度以及颈动脉斑块积分均显著改善（P〈0.05,P＜0.01）.治疗后PAS组TC、LDL-C、TNF-α水平与AS组差异均有统计学意义（P＜0.01）.结论 治疗血脂紊乱的老年颈动脉粥样硬化患者,他汀类药物结合抗血小板类药物通过调节血脂、抗炎,起到抗动脉粥样硬化的作用,加用普罗布考可以发挥更显著的疗效.     

Comparative effect of melatonin and vitamin E on phenylhydrazine-induced toxicity in the spleen of Funambulus pennanti

Phenylhydrazine (PHZ) oxidation resulting in free iron release followed by free radical generation has increased frequency of cancer. This study aims towards the dose-dependent response of PHZ and the role of melatonin in comparison with vitamin E following PHZ-induced toxicity within the lymphoid tissue (spleen) of Indian tropical seasonal breeder, Funambulus pennanti, during reproductively active phase. An increase in the damages in terms of lipid peroxidation (LPO), apoptosis percentage, and splenomegaly was observed following different doses of PHZ treatment, i.e., 0.025, 0.5, and 1 mg/100 g body weight (b.wt.), where dose of 1 mg/100 g b.wt. showed more significant damages. Both melatonin (0.5 mg/100 g b.wt.) and vitamin E (1 mg/100 g b.wt.) administration ameliorated oxidative damages of 1 mg/100 g b.wt. PHZ-treated group. Melatonin altered PHZ-induced responses significantly to a greater degree than vitamin E as evidenced by LPO status, SOD activity, and ABTS radical cation scavenging activity of antioxidants. Thus, melatonin might be able to restrict carcinogenic property of PHZ-induced oxidative stress by protecting macromolecules of the cell from harmful effects of PHZ and instead preserving cell viability.     

Nimesulide in the treatment of advanced cancer pain. Double-blind comparison with naproxen.

In a clinical double-blind study, the analgesic efficacy and the side-effects of nimesulide (Aulin, CAS 51803-78-2) and naproxen administered to 68 patients affected by advanced cancer pain were compared. Patients were treated with non-steroidal anti-inflammatory drugs according to the first step of the pharmacological analgesic scale of the WHO. The dose administered was 200 mg b.i.d. (every 12 h) for nimesulide and 500 mg b.i.d. (every 12 h) for naproxen. From this study the analgesic effect and the tolerability of the two drugs appeared to be similar. Both drugs resulted to be effective with a low incidence of adverse events that may be related to their use.     

Subacute toxicity of alpha-ergocryptine in Sprague-Dawley rats. 2: metabolic and hormonal changes.

The present study describes the metabolic changes observed in a dietary subacute toxicity experiment with the ergot alkaloid alpha-ergocryptine in Sprague-Dawley rats. The observed effects on metabolic and hormonal parameters were described separately from the general toxicological effects, in view of the important role of dopamine agonists in metabolism (e.g. ergot alkaloids in fescue toxicosis). The rats were fed 0, 4, 20, 100 or 500 mg ergocryptine/kg diet for 28-32 days (equal to 0, 0.36, 1.7, 8.9 and 60 mg ergocryptine/kg body weight/day for females and 0, 0.34, 1.4, 6.6 and 44 mg ergocryptine/kg body weight/day for males). Total cholesterol and high-density lipoprotein (HDL)-cholesterol were decreased dose dependently in females but the ratio HDL-cholesterol/total cholesterol was only decreased at 20 mg/kg body weight. Triglycerides and glucose concentrations were decreased in the highest dose groups of both sexes. Serum urea concentrations were increased in the 20, 100 and 500 mg/kg dose groups. Insulin, glucagon and liver glycogen were increased in the highest dose group at the end of the study, when the animals were allowed to eat prior to blood sampling and necropsy. Prolactin, T4 and FT4 were decreased in the 20, 100 and 500 mg/kg dose groups of both sexes. Follicle-stimulating hormone (FSH) was decreased in the 20, 100 and 500 mg/kg female dose groups and luteinizing hormone (LH) was increased in the 20, 100 and 500 mg/kg male dose groups. It is postulated that the observed effects on food intake, metabolism (lipid and carbohydrate) and hormonal parameters are due to an interaction of ergocryptine with central dopaminergic activities, which comprise a major functional component of a central regulatory system for metabolism.     

Antihyperlipidemic potential of Cedrus deodara extracts in monosodium glutamate induced obesity in neonatal rats

Objective:

To study the antihyperlipidemic effect of Cedrus deodara (C. deodara) against monosodium glutamate (MSG) induced obesity in neonatal rats.

Materials and Methods:

The studies were carried out on newborn neonatal rats and were injected intraperitoneally with 2 mg/g of MSG on the 2^nd and 4^th postnatal days and 4 mg/g on 6^th, 8^th and 10^th postnatal days. Ethanolic extract (EE) and acetone extract (AE) of C. deodara was administered in a dose of 100 and 200 mg/kg, p.o./day at the age of 65 days. On day 60 of treatment, body weight, locomotor activity, body temperature, and various biochemical parameters like serum glucose, total cholesterol, triglyceride, and organs weights were recorded.

Results:

There was a significant reduction in body weight, organs and increased body temperature, locomotor activity after treatment with extracts. C. deodara decreased serum glucose, total cholesterol and triglyceride, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels and increased high density lipoprotein (HDL) significantly has compared to MSG-control rats.

Conclusion:

C. deodara extracts exhibited antihyperlipidemic effect and it possesses anti-obesity properties in MSG induced obese rats.KEY WORDS: Antihyperlipidemic, Cedrus deodara, monosodium glutamate, neonatal, obesity     

Deleterious effects of 28-day oral co-administration of first-line anti-TB drugs on spleen,blood and bone marrow chromosomes in normal rat

Context: Isoniazid, rifampicin and pyrazinamide are most reliable and cost-effective remedy for tuberculosis treatment and prophylaxis among first-line anti-tuberculosis (TB) drugs and have a pronounced tendency to cause adverse drug reactions. Hepatotoxicity is well-studied side effect of these drugs but their effects on other organs like spleen and blood are still needed to be explored. Objective: To explore the probable outcome of co-administration these three major antitubercular drugs (ATDs), rifampicin, isoniazid and pyrazinamide on spleen, blood and bone marrow. Materials and methods: Different parameters were evaluated like lipid peroxidation, glutathione (GSH) and protein content in spleen by spectrophotometric evaluation, hematological evaluation by determining total hemoglobin, total leukocyte count, differential leukocyte count and scanning electron microscopy studies in blood, genotoxicity studied by bone marrow chromosomal analysis and DNA fragmentation. The female rats n?=?12 (150–200?g) were grouped as control group orally given saline and toxicant group given INH (30.85?mg/kg b.wt.)?+?RIF (61.7?mg/kg b.wt.) +?PZA (132.65?mg/kg b.wt.) dosage extrapolated from dose that is used in human for 28 d once daily. Results: After 28 d-oral co-administration of anti-TB drugs (INH (30.85?mg/kg b.wt.)?+?RIF (61.7?mg/kg b.wt.) +?PZA (132.65?mg/kg b.wt.)), it was revealed that there were an increase thiobarbituric acid reactive substances, decrease in GSH and protein contents in spleen. Marked changes in hematological parameters, DNA fragmentation and chromosomes were also observed. Conclusion: This can be concluded from this work that co-administration of first-line ATDs is toxic to spleen and blood also these drugs can cause damage at genetic level.     

不同剂量瑞舒伐他汀对老年缺血性脑卒中患者血脂的影响

目的观察不同剂量瑞舒伐他汀钙对老年缺血性脑卒中患者血脂的影响。方法随机将50例血脂异常的老年缺血性脑卒中患者分为低剂量瑞舒伐他汀钙治疗组(5mg)和高剂量瑞舒伐他汀钙治疗组(10mg),每组25例,分别于治疗前、治疗后8周观察血脂水平变化。结果治疗8周后,二组患者总胆固醇(TC)、低密度脂蛋白(LDL-C)和三酰甘油(TG)水平均降低(P<0.01),高密度脂蛋白(HDL-C)升高(P<0.01),高剂量治疗组均优于低剂量治疗组(P<0.05)。结论不同剂量瑞舒伐他汀钙(5、10 mg)都能有效改善老年缺血性卒中患者血脂水平。     

Pharmacological comparison of the statins

The statins (3-hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors) represent drugs of first choice for treatment of hypercholesterolemia. The safety and efficacy of atorvastatin (CAS 134523-00-5), simvastatin (CAS 79902-63-9), lovastatin (CAS 75330-75-7), pravastatin (CAS 81093-37-0) and fluvastatin (CAS 93957-54-1) has been well documented. Statins decrease dose-dependently low-density lipoprotein (LDL) cholesterol as well as coronary events and total mortality. Clinical outcome data indicate that for simvastatin the lowest number of treated patients is needed to prevent one major coronary event (NNT 15). Based on an approximately 30% reduction of LDL (valid surrogate parameter) atorvastatin (5 mg/day) and simvastatin (10 mg/day) are the most potent agents whereas 40 mg of lovastatin or pravastatin and 60 mg of fluvastatin are needed to reach this "therapeutic target". While all statins share the same mode of action their pharmacokinetic properties and their susceptibility to drug interactions differ slightly. Agents inhibiting CYP3A4 (e.g. grapefruit juice, itraconazole, cyclosporine) should be discouraged if a patient is on atorvastatin, lovastatin or simvastatin. Likewise, fluconazole interferes with the CYP2C9-mediated hepatic elimination of fluvastatin. Moreover, coadministration of gemfibrozil should be avoided because it seems to increase the very low risk for statin-induced rhabdomyolysis. Several statins are available and their equieffective doses have been defined. Selection of a particular drug should be primarily based on clinical outcome data. However, costs and in certain situations the pharmacokinetic profile including the interaction potential of the statins should be taken into account.     

Influence of chrysin on hepatic marker enzymes and lipid profile against d-galactosamine-induced hepatotoxicity rats

Chrysin is a flavonoid that exists in nature and is the major component of some traditional medicinal herbs. We investigated the hepatoprotective and antihyperlipidaemic potential of chrysin against d-galactosamine (a single intraperitoneal injection 400 mg/kg BW) induced hepatotoxicity in male albino Wistar rats. d-GalN rats exhibited an increased hepato and nephro toxicity marker activities aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma glutamyl transpeptidase and total bilirubin level while urea, uric acid and creatinine and lipid profile. It also negatively affected the serum total protein, albumin and A/G ratio. Rats treated with chrysin at different concentrations (25, 50 and 100 mg/kg BW) caused a significant improvement in serum protein level, decreased hepato and nephro toxicity markers. It also decreased the levels of very low density lipoprotein cholesterol and low density lipoprotein cholesterol while high density lipoprotein cholesterol significantly increased. It also decreased the levels of total cholesterol, phospholipids, triglycerides, free fatty acids in the plasma and tissues of liver and kidney. The effect of chrysin (25 mg/kg) is comparable with silymarin, a known hepatoprotective drug. Chrysin thus exhibits hepatoprotective and antihyperlipidaemic activity.     

Atorvastatin plus pravastatin for the treatment of heterozygous familial hypercholesterolaemia--a pilot study

The most common side-effect of statins, mainly during dose titration, is liver toxicity, In these cases, sufficient control of low density lipoprotein cholesterol (LDL-C) in patients with heterozygous familial hypercholesterolaemia (HFH) becomes problematical. In patients with intolerance to resins as well, especially in the presence of coronary artery disease (CAD), it is practically impossible to reach the LDL-C treatment goal. This study included seven HFH patients with CAD, who presented with alanine amino transferase levels greater than three times the upper normal limit during dose titration of atorvastatin or simvastatin of from 20 mg/day to 40 mg/day. They could not tolerate concomitant cholestyramine administration, and presented with LDL-C levels significantly higher than the treatment goal (100 mg/dl; 2.6 mmol/l). In these patients, a combination of two statins with different pharmacokinetics (20 mg/day of atorvastatin plus 40mg/day of pravastatin) was administered for a mean period of one year. Efficacy was compared with that of monotherapy with each drug alone and with that of 40 mg of atorvastatin in 13 patients, who could also not tolerate resin co-administration, and that of 40 mg/day of atorvastatin plus 12 g of cholestyramine in 30 patients, with similar pretreatment LDL-C levels. No increase in serum transaminases and no symptom or sign of myopathy was recorded during the administration of the combination of the two statins for a mean period of 12 months. The atorvastatin plus pravastatin regimen was more effective than both monotherapies and equally effective with the 40 mg of atorvastatin and the 40 mg of atorvastatin plus 12 g of cholestyramine regimens in reducing LDL-C (59% vs. 57% and 61%, respectively) and triglyceride levels (31% vs. 32% and 28%, respectively), while it also had a better effect on high density lipoprotein cholesterol (13% vs. 7% and 8%). The data suggest that the atorvastatin-pravastatin combination has a highly beneficial effect on all lipid parameters, without causing hepatotoxicity, in HFH patients with CAD who are sensitive to higher doses of statins in monotherapy. These results require confirmation in larger studies.