Association Study of SLCO1B3 and ABCC3 Genetic Variants in Gallstone Disease.

There is growing evidence that gallstone formation may be genetically determined. Recent studies have shown that polymorphism of genes encoding proteins involved in bile acid transport may be associated with the risk of gallstone disease. The aim of this study was to investigate the association between SLCO1B3 (rs4149117:G>T, rs7311358:A>G) and ABCC3 (rs4793665:T>C, rs11568591:G>A) genetic variants and susceptibility to cholesterol gallstone disease, as well as gallstone composition. The study included 317 patients suffering from cholelithiasis who underwent cholecystostomy and 249 controls with no evidence of stones, confirmed by ultrasound examination. There were no statistically significant differences in the distribution of studied gene polymorphisms between patients with gallstone disease and healthy controls. No significant associations were observed between studied genotypes and the content of analyzed gallstone components: total cholesterol, bilirubin, CaCO3, nor the total bile acids. There was also no association between bile acid content in gallstones and the polymorphisms studied. The results of this study suggest that polymorphisms of SLCO1B3 and ABCC3 genes are not a valuable marker of gallstone disease susceptibility and do not influence gallstone composition.

SLC22A5 polymorphism associated with risk of extra-articular manifestations in rheumatoid arthritis patients.

OBJECTIVES: Rheumatoid arthritis (RA), the most common autoimmune disease, is thought to be a complex disease in which a combination of risk alleles from different susceptibility genes predisposes to development of the disease, following exposure to as yet unknown environmental factors. An important component of the carnitine system is the plasma membrane carnitine transporters, also called organic cation transporters, i.e. OCTN1 and OCTN2 encoded by the SLC22A4 and SLC22A5 genes, respectively. The aim of this study was to investigate the association between SLC22A5 polymorphism and RA. MATERIAL AND METHODS: The study was carried out on 404 patients diagnosed with RA according to the criteria of the American College of Rheumatology and 560 healthy subjects. The single nucleotide polymorphism (SNP) within the SLC22A5 gene - 207C>G (rs 2631367) was genotyped using pre-validated TaqMan genotyping assays. RESULTS: The distribution of SLC22A5 genotypes and alleles in RA patients did not differ significantly from that in healthy controls. Moreover, there were no significant associations between SLC22A5 genotypes and age at time of disease diagnosis, rheumatoid factor, erosive disease and response to treatment with methotrexate. Extra-articular manifestations were diagnosed in 16.7% of SLC22A5 GG homozygous patients, in 9.4% with the GC genotype and in 7.2% of homozygous CC patients. The frequency of extra-articular manifestations was two-fold greater in homozygous GG patients as compared with carriers of the C allele (GG vs. GC + CC), OR = 2.06 (95% CI: 1.11-3.85, p = 0.022). CONCLUSIONS: The results of the present study suggest that the SLC22A5 polymorphism may be associated with the development of extra-articular manifestations of RA but the distribution of SLC22A5 genotypes and alleles in studied RA patients did not significantly differ from healthy subjects.

TNF-α and IL10 gene polymorphisms in women with postmenopausal osteoporosis.

OBJECTIVE: Postmenopausal osteoporosis is a common disorder characterized by decreased bone mineral density (BMD). Proinflammatory cytokines are among the significant factors involved in bone turnover. They are the stimulants of bone resorption, acting directly on osteoclasts and osteoclast precursors. In this study, we examined the TNF-α (-308G>A) (rs1800629) and IL10 (-1082G>A) (rs1800896), (-592C>A) (rs1800872) polymorphisms in postmenopausal women with BMD T-scores less than and greater than or equal to -2.5 SD. STUDY DESIGN: This study included 224 postmenopausal women with BMD T-scores lower than -2.5 SD (mean: -3.02±0.53) and 238 postmenopausal women with BMD T-scores -2.5 SD and greater (mean: -1.33±0.51). RESULTS: There was a decrease in the frequency of IL10 1082 G allele carriers (GG and GA genotypes) in women with T-scores below -2.5 SD (GG+GA vs AA: OR=0.65, 95% CI=0.44-0.97, p=0.037). With regard to the TNF-α -308 G>A polymorphism, in the women with T-scores below -2.5 SD, the increased frequency of GG homozygotes and G allele carriers was detected (AA+GA vs GG: OR=0.54, 95% CI=0.35-0.82, p=0.004). CONCLUSIONS: The results of our study suggest an association between TNF-α -308G>A and IL10 -1082G>A polymorphisms and postmenopausal osteoporosis.

Can we predict urinary stone composition based on an analysis of microelement concentration in the hair and urine?

BACKGROUND: In recent years the role of trace elements in lithogenesis has received steadily increasing attention. OBJECTIVES: This study was aimed to attempt to find the correlations between the chemical content of the stones and the concentration of chosen elements in the urine and hair of stone formers. MATERIAL AND METHODS: The proposal for the study was approved by the local ethics committee. Specimens were taken from 219 consecutive stone-formers. The content of the stone was evaluated using atomic absorption spectrometry, spectrophotometry, and colorimetric methods. An analysis of 29 elements in hair and 21 elements in urine was performed using inductively coupled plasma-atomic emission spectrometry. RESULTS: Only a few correlations between the composition of stones and the distribution of elements in urine and in hair were found. All were considered incidental. CONCLUSIONS: The data obtained did not allow for the creation of a proper and practical algorithm to predict stone chemical composition based on hair and urine analysis.

The effect of retinoic acid receptor agonist acitretin on the production of bile and concentrations of some serum components in ovariectomized rats.

OBJECTIVE: Acitretin is an oral retinoid that is approved for the treatment of psoriasis and in the chemoprevention of nonmelanoma skin cancer. The metabolism of acitretin occurs in the liver and may affect other metabolic processes in the liver, such as metabolism of bilirubin, bile acids, and lipids. These processes may be also affected by physiologic loss of estrogens in postmenopausal women. Therefore, the aim of this study was to examine the effect of acitretin on the secretion and composition of bile and the turnover of cholesterol in a model of estrogen deficiency in ovariectomized rats. METHODS: The study was carried out on female Wistar rats divided into three groups: sham-operated control, ovariectomized control, and ovariectomized rats receiving acitretin. The studied group was administered acitretin (Neotigason capsules 25 mg, Roche; 7.1 mg/kg body weight per 24 h) for 28 days. Bile fractions and blood were collected for determinations of concentration of bile acids, total cholesterol, calcium ions, chloride ions, and direct bilirubin. In addition, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were assayed. RESULTS: It was found that ovariectomy produced alterations in the process of secretion of bile and its principal components: cholesterol, bile acids, chloride ions, and bilirubin. The administration of acitretin decreased the secretion of bile and bile cholesterol, as well as serum levels of total, LDL, and HDL cholesterol, and moreover increased the proportion of bile acids to total cholesterol. CONCLUSIONS: Acitretin may influence the hepatic metabolism of bile, bile acids, and lipids. This action is associated with a decrease in factors influencing the lithogenicity of bile, with reductions in the serum levels of total, LDL, and HDL cholesterol.

N-acetyltransferase 2 (NAT2) polymorphism in patients with atopic asthma.

BACKGROUND AND AIMS: Allergic asthma is a chronic inflammatory disorder of the airways where, on exposure to allergens, the body mounts an immune response. The etiology of asthma is complex and multifactorial. Rapid and slow acetylators reflect the genetically determined variation in the elimination of xenobiotics. Recent advances have demonstrated the importance of genetic and environmental factors in the development of atopic asthma. Hepatic arylamine N-acetyltransferase 2 (NAT2) takes part in the detoxification of some drugs and arylamine xenobiotics. The aim of the present study was to determine the NAT2 polymorphism in patients with atopic asthma. METHODS: In the study, 184 unrelated asthmatic patients and 181 healthy controls were included. The mutations at positions 481T, 803G, 590A and 857A of the NAT2 gene were determined by a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: The frequency of homozygous fast acetylators did not differ significantly between patients and controls. Compared with the control population, the significant prevalence of slow acetylators in the group of patients with atopic asthma was observed. There was a statistically significant prevalence of subjects with NAT2*5/NAT2*5 and NAT2*5/NAT2*6 genotypes. The risk of an atopic asthma development was 3.4 times greater in slow than in fast acetylators (OR = 3.3657; p <0.000001, 95% CI = 2.1282-5.3228). CONCLUSIONS: These results suggest that NAT2 polymorphism may be involved in the pathogenesis of atopic asthma.

IL-1beta, IL-6, and TNF gene polymorphisms do not affect the treatment outcome of rheumatoid arthritis patients with leflunomide.

Leflunomide is an isoxazole derivative that is structurally and functionally unrelated to other known immunomodulatory drugs. Previous studies have revealed that therapy with leflunomide causes decreased production of mediators such as IL-1beta, IL-6, and TNF-alpha, which are involved in inflammatory process. The aim of the present study was to examine whether the polymorphisms in genes IL1B, IL6, and TNF may affect treatment outcomes in RA patients treated with leflunomide. The study was carried out on 129 patients (106 women, 23 men, mean age 52.9 +/- 11.03) diagnosed with RA and treated with leflunomide 20 mg daily. Clinical improvement was evaluated according to the American College of Rheumatology (ACR) 20% and 50% response criteria. There were no statistically significant associations between the studied genotypes and improvement of disease activity parameters. The results of the present study suggest that IL1beta, IL6, and TNF gene polymorphisms are not significant factors influencing the therapy outcome of RA patients with leflunomide.

The association between cytokine gene polymorphisms and kidney allograft survival.

BACKGROUND: Cytokines regulate cellular and humoral immune responses. One determinant of the variable cytokine production observed among individuals is genetic polymorphism in cytokine genes. These polymorphisms represent normal allelic variations in the cytokine genes; usually single base changes. Homozygous genotypes for high producer alleles are generally associated with high cytokine production, heterozygotes with intermediate production, and homozygotes for the low producer alleles with low cytokine production. Cytokines have been implicated in the regulation of acute and chronic rejection of allografts. The aim of the study was to evaluate the promoter polymorphism of TNF-alpha gene (-308 promoter polymorphism), IL-2 gene (-330 promoter polymorphism), IL-4 gene (-590 promoter polymorphism), and IL-6 gene (-174 promoter polymorphism) in renal transplant recipients with allograft duration under and over 10 years to establish whether aforementioned polymorphism are involved in kidney allograft survival. MATERIAL/METHODS: The study included 197 renal transplant recipients with well-functioning grafts for 2 to 18 years. The patients were divided into two subgroups: recipients with allograft duration under 10 years and recipients with allograft duration over 10 years. RESULTS: Among renal transplant recipients with allograft duration over 10 years we observed the prevalence of subjects with the T1T1 genotype of TNF alpha (low expression of TNF alpha) and GG of IL-6 (high expression of IL-6). There was no difference in relation to IL-2 and IL-4 promoter polymorphism. CONCLUSIONS: The results of present study suggest that the TNF-alpha -308 and the IL-6 -174 promoter polymorphisms may be the genetic factors influencing the renal allograft survival.

Effect of artichoke extract (Cynara scolymus L.) on palmitic-1-14C acid oxidation in rats.

Studies on the effect of the artichoke extract (AE) on oxidation of palmitic-1-14C acid administered intravenously to rats at a dose 25 and 50 mg/kg bw demonstrated marked enhancement of both 14CO2 expiration rate and 14CO2 recovery in the expired air. The extract suppressed accumulation of palmitic-1-14C acid in serum lipids and epididymal fat pad tissue as well. The effects of the extract on 14CO2 expiration rate, 14CO2 recovery, as well as accumulation of palmitic-1-14C acid were dose dependent. Total14CO2 recovery in expired air during 60 min was elevated by 17.3% (p < 0.05) and 52.1% (p < 0.001) in rats administered the extract at a dose of 25 and 50 mg/kg, respectively. The rats supplemented with the AE at a dose of 25 and 50 mg/kg bw were characterized by 10.0% (not significant) and 19% (p < 0.05) decrease in( 14)C radioactivity of serum lipids as well as reduction of epididymal fat tissue 14C radioactivity by 8.7 and 17.5% (p < 0.05), respectively, in comparison with the control rats. Thus, the results demonstrate that the AE possess stimulatory properties with respect to oxidation of palmitic acid administered to rats, and provide new information on the mechanism of antilipemic activity of the extract associated with activation of lipid oxidation in the organism.

Cholesterol 7alpha-hydrolase (CYP7A1) c.-278A>C promoter polymorphism in gallstone disease patients.

There is growing evidence that gallstone formation may be genetically determined. Cholesterol 7alpha-hydrolase (CYP7A1) is an enzyme that catalyzes the first, rate-limiting reaction of cholesterol catabolic pathway. Recently, a common c.-278A>C polymorphism (rs3808607:G>T) has been described in CYP7A1 gene, associated with altered plasma lipid levels. The aim of this study was to verify the finding that CYP7A1 polymorphism may be associated with gallstone disease. Frequency and distribution of the studied alleles did not differ significantly between the patients (-278C; minor allele frequency: 0.45) and the controls (0.48). No significant gender-related differences of allele frequencies or distribution were noted. We conclude that CYP7A1 promoter polymorphism is not a valuable marker of gallstone disease susceptibility in a Polish population.

[Gall bladder stones during pregnancy in the age of laparoscopic cholecystectomy]. / Kamica zólciowa w ciazy, w dobie cholecystektomii laparoskopowej.

Not all pregnant women with gall bladder stones can be treated conservatively--some of them require surgery. The main indications for cholecystectomy are the following: repeated episodes of biliary colic and acute cholecystitis. There is no data indicating which moment during the pregnancy may be the safest to perform the operation. Nowadays, laparoscopic cholecystectomy is more often performed than the traditional procedure. Initial reports about unfavorable results of laparoscopic procedures during pregnancy were not confirmed later on. In most medical centers the preparation of pregnant women for the laparoscopic cholecystectomy, as well as operating technique and postoperative management, do not differ significantly from the management of other patients. There is a general agreement that laparoscopic surgery in case of pregnant patients requires not only a close cooperation between the surgeon and the obstetrician, but also a lot of experience in the laparoscopic technique itself. Further research and publications are needed on this topic, as they might prove the clinical value of this kind of management by showing a significant number of observations regarding laparoscopic cholecystectomies in pregnant women. It is true not only of surgeons but also of the obstetricians.

Apolipoprotein B (APOB) gene polymorphism in patients with gallbladder disease.

Cholelithiasis is one of the most prevalent gastroenterological diseases, precipitated mainly by environmental factors. However, twin studies provided strong evidence for a role of genetic factors in the disease pathogenesis. An association between plasma lipoprotein levels and gallstone disease (GSD) was presented. Apolipoprotein B is an essential structural component of triglyceride-rich lipoprotein particles and plays an important role in the maintenance of cholesterol homeostasis in mammals. Various studies have shown a relationship between APOB gene polymorphisms and lipoprotein levels, but only few investigated a potential association between APOB polymorphism and GSD, giving contrary results. In the current study, an association between common polymorphisms in APOB gene (T2488T and E4154K) and cholesterol gallstone disease was examined. Two hundred and forty patients of Caucasian origin suffering from cholelithiasis, as well as 217 healthy individuals, were included in the study. Patients were genotyped for two single nucleotide polymorphisms (SNPs) in APOB gene: 2488C>T (XbaI), and 4154G>A (EcoRI) using PCR-RLFP method. The resulting analysis has shown that polymorphic loci in positions 2488 and 4154 in APOB gene are in full linkage in a Polish population and form only three haplotypes: 2488C-4154G, 2488T-4154G and 2488C-4154A. Frequency and distribution of 2488C>T alleles did not differ significantly between patients and controls. The 4154G allele has been found to be associated with GSD (p=0.001). A risk of gallstone formation was reduced in 4154AA homozygotes (OR=0.25, p=0.009) and heterozygous individuals (OR=0.63, p=0.03) as compared to 4154GG homozygotes. Additionally, 2488C-4154A haplotype was identified as a protective factor against GSD (p=0.04). Our results suggest that SNPs in APOB, potentially considered as one of lith genes as well as certain haplotypes, may be risk factors for GSD.

Colchicine against ischemia-reperfusion injury in experimental lung transplantation.

BACKGROUND: To asses the influence of colchicine, a potent antinflammatory agent and neutrophile migration inhibitor, on Ischemia-Reperfusion Injury (IRI) in rat lung isogeneic transplantation. MATERIAL/METHODS: Isogeneic, orthotropic single left lung transplantations were performed among male Wistar rats after total ischemic graft storage time of 12 or 18 hours in temperature of 4 degrees C. Recipients received either no specific treatment (control) or Colchicine 1.2 mg/kg/d ip. Twenty-four hours after transplantation, the native contralateral lung was occluded to assess graft gas exchange function (PaO(2)). The lung graft was excised and assessed for Wet/Dry ratio (W/D) as a measure of edema, Myeloperoxidase activity (MPO) as a measure of neutrophile migration and histology. RESULTS: PaO(2) differences were not significant among all groups. Comparing colchicine to control group, the W/D ratio 3.93+/-0.66 vs. 1.86+/-0.32, p=0.002 and MPO 8.1+/-3.34 vs. 5.87+/-1.76, p=0.046 were significantly higher for 18 hours colchicine group. Comparing 18 to 12 hours time groups, the W/D ratio 5.70+/-1.53 vs. 1.86+/-0.32, p=0.007 for control groups and 5.40+/-1.49 vs. 3.93+/-0.66, p=0.049 for colchicine groups were significantly higher for both 12 h groups. Histology favored colchicine treated animals. CONCLUSIONS: Colchicine in tested dose does not decrease edema after lung transplantation and does not improve lung function. 18 vs. 12 hours total ischemic graft storage time causes less lung edema.

Effect of tamoxifen and raloxifene on the conjugation of bile acids with taurine and glycine in ovariectomized rats.

The selective estrogen receptor modulators tamoxifen and raloxifene represent a major therapeutic advance for clinical practice. Unlike estrogens, which are uniformly agonists, tamoxifen and raloxifene exert selective agonistic or antagonistic effects on various estrogen target tissues. The aim of the study was to evaluate the influence of tamoxifen and raloxifene on the conversion of cholesterol to bile acids in estrogen deficiency in rats. The study included 40 female Wistar rats. The animals were divided into four groups: sham operated control, ovariectomized control, ovariectomized rats treated with tamoxifen ovariectomized rats treated with raloxifene. After 42 days of drug administration, bile was collected under anesthesia after administration of radioactive 4-(14)C cholesterol. Bile was assayed for concentration of (14)C bile acids conjugated with taurine and glycine after thin-layer chromatography separation by the use of isotopic technique. In rats treated with tamoxifen and raloxifene, the statistically significant increase in concentration of bile acids conjugated with glycine was observed as compared to ovariectomized animals from control group. Moreover, in rats treated with tamoxifen the concentration of bile acids conjugated with taurine significantly increased. The results of the present study suggest that tamoxifen and raloxifene increase the concentrations of conjugated bile acids in bile.

Effect of 4-hydroxyandrost-4-ene-3,17-dione (formestane) on the bile secretion and metabolism of 4-(14)C-cholesterol to bile acids.

4-Hydroxyandrost-4-ene-3,17-dione (formestane) is a selective aromatase inhibitor. It is indicated for postmenopausal patients with advanced breast cancer. The aim of the present study was to investigate the effect of 4-hydroxyandrost-4-ene-3,17-dione on the bile secretion and metabolism of 4-(14)C-cholesterol to bile acid. The experiments were carried out in the ovariectomized and sham-operated female Wistar rats. Formestane (20 mg/kg, i.m., daily) was administered to animals for 2 weeks. Twenty four hours after the last drug administration, rats were anesthetized with ethyl urethane. 4-(14)C-cholesterol (740 kBq/kg, s.a. 2.28 GBq/mmol) was infused for 1 min by catheter inserted into the jugular vein. Bile samples were assayed for total 14C radioactivity 14C-bile acids were determined in bile (after thin-layer chromatographic separation) by the use of isotopic technique with liquid scintillator. Previous studies showed that systemic adverse effects occurred in about 12% of patients following intramuscular drug administration. Many of them such as hot flushes, vaginal spotting and emotional lability were related to the mechanism of action of formestane i.e. estrogen suppression. Lethargy, rash, nausea, dizziness, indigestion, ataxia, cramps and facial swelling have also been reported. The results of the present study have shown that formestane administered to the female ovariectomized rats decreased the bile secretion and diminished conversion of 4-(14)C-cholesterol to trihydroxy bile acids. The decreased synthesis of trihydroxy bile acids and increased concentrations of cholesterol and litocholic acid in bile may be associated with increased risk of gallstone formation.

Effect of tibolone on turnover of cholesterol to bile acids in ovariectomized rats.

OBJECTIVE: Tibolone is used in breast cancer therapy in women. The most important aspect of this therapy concerns its influence on bone and lipid metabolism. Several studies have reported the effect of tibolone on plasma lipids. Approximately 40% of total cholesterol removal occurs by its conversion to bile acids, a process that takes place in the liver. The aim of the study was to evaluate the influence of tibolone on the conversion of cholesterol to bile acids in estrogen-deficient rats. DESIGN: Thirty female Wistar rats were divided into three groups: sham-operated controls, ovariectomized controls, and ovariectomized rats treated with tibolone. After 42 days of drug administration, bile was collected under anesthesia after administration of radioactive 4-C cholesterol. Bile was assayed for total C radioactivity; C bile acids were determined after thin-layer chromatography separation by using the isotopic technique. RESULTS: The ovariectomy decreased the concentrations of C-radioactive bile, taurocholic acid, and cholic acid. The administration of tibolone significantly increased the excretion of C-radioactive bile and C-radioactive bile acids as compared with ovariectomized controls. Moreover, the therapy with tibolone significantly increased the concentrations of C taurocholic acid, C glycocholic acid, cholic acid, and taurochenodeoxycholic plus taurodeoxycholic acids. CONCLUSION: The results of the present study suggest that tibolone may increase the concentrations of cholesterol and trihydroxy bile acids in bile. These changes may be associated with an increased risk of gallstone generation.

Effect of tamoxifen and raloxifene on cholesterol transformation to bile acids in ovariectomized rats.

Tamoxifen is used as adjuvant therapy for prevention and treatment of metastatic breast cancer, whereas raloxifene is approved for osteoporosis and is being investigated for breast cancer prevention. The most important aspects of these therapies are focused on their influence on bone and lipid metabolism. Several studies have reported the effect of tamoxifen and raloxifene on plasma lipids. Approximately 40% of total cholesterol removal occurs by conversion to bile acids, a process that takes place in the liver. The aim of the present study was to evaluate the influence of tamoxifen and raloxifene on the conversion of cholesterol to bile acids in estrogen-deficient in rats. The study included 40 female Wistar rats, divided into four groups: sham-operated controls, ovariectomized controls, ovariectomized rats treated with tamoxifen and ovariectomized rats treated with raloxifene. After 42 days of drug administration, bile was collected under anesthesia following administration of radioactive [4-(14)C]cholesterol and assayed for total (14)C radioactivity; (14)C-labeled bile acids were determined by the use of isotopic techniques after initial separation by thin-layer chromatography. Ovariectomy caused decreased excretion of bile and bile acids. Administration of tamoxifen and raloxifene significantly reduced the excretion of (14)C-labeled bile and bile acids compared with ovariectomized controls. Tamoxifen therapy significantly reduced the excretion of taurocholic acid and glycochenodeoxycholic plus glycodeoxycholic acids, and excretion of cholic, litocholic and chenodeoxycholic plus deoxycholic acids was increased. Raloxifene significantly reduced the excretion of taurocholic, glycocholic and litocholic acids, taurochenodeoxycholic plus taurodeoxycholic acids, as well as chenodeoxycholic plus deoxycholic acids. The results of the present study suggest that tamoxifen and raloxifene did not reverse the changes in bile composition induced by estrogen deficiency. The decreased concentration of trihydroxy bile acids during therapy with raloxifene might decrease the risk of gallstone formation, although this hypothesis requires further investigation.

Effect of tamoxifen, raloxifen and tibolon on bile components in ovariectomized rats.

The aim of the study was to investigate the effect of ovariectomy on the bile composition in order to estimate the ability of selective estrogen receptor modulators (SERMS) (tibolon, tamoxifen, raloxifen) to modify the ovariectomy-induced disorders. The study was carried out on the ovariectomized female Wistar rats. Tibolon (1 mg kg(-1) 24 h(-1)), tamoxifen (5 mg kg(-1) 24 h(-1)) and raloxifen (10 mg kg(-1) 24 h(-1)) were administered for 42 days. Under anesthesia bile was collected during 6h period. The ovariectomy increased significantly the excretion of biliary acids and calcium in bile and decreased the excretion of cholesterol and chloride. In rats treated with tamoxifen and raloxifen the excretion and concentration of cholesterol in bile were significantly reduced in comparison with ovariectomized rats. In rats treated with tibolon these values were increased. Moreover in rats treated with tamoxifen and raloxifen the concentrations of calcium in bile were significantly reduced. Tibolon had no significant effect on bile calcium concentrations. The therapy with tamoxifen, raloxifen and tibolon decreased the serum cholesterol concentrations, whereas the bile acid concentrations were increased in comparison with ovariectomized control. The drugs studied had no significant effect on calcium and chloride serum concentrations. Our results suggest that the therapy with tamoxifen and raloxifen may have the positive effect on bile composition in ovariectomized rats and probably may prevent the gallstone formation.

The effect of tamoxifen and fluoride on bone mineral density, biomechanical properties and blood lipids in ovariectomized rats.

The most important aspect of therapy with fluoride and tamoxifen concerns its influence on bone tissue and lipid metabolism. The aim of the study was to evaluate the effect of tamoxifen and natrium fluoride (NaF) on bone metabolism, biochemical properties and blood lipids levels in ovariectomized rats. The study was performed in Wistar rats divided into 5 subgroups: ovariectomized controls, rats treated with NaF 20 mg/kg/24 hr, rats treated with NaF 20 mg/kg/24 hr+tamoxifen 2 mg/kg/24 hr, rats treated with NaF 20 mg/kg/24 hr plus tamoxifen 4 mg/kg/24 hr, and sham-operated controls. In ovariectomized rats the increase of total cholesterol, low-density lipoproteins cholesterol (LDL-cholesterol) as well as the decrease of bone mineral content, bone mineral density and biomechanical properties was observed. The therapy with NaF increased the level of total cholesterol, LDL-cholesterol, triglycerides, bone mineral density, bone mineral content. In this group the decrease of bone strength and stiffness was observed. The administration of tamoxifen reduced the changes in plasma lipid levels, but did not improve the biomechanical properties of bone tissue.

Effect of tamoxifen on bone mineral density and blood lipids in ovariectomized rats.

Tamoxifen is widely used in breast cancer therapy and in the treatment of all stages of breast cancer including chemoprevention in women at high risk of the disease. The most important aspect of tamoxifen therapy concerns its influence on bone tissue and lipid metabolism. The aim of the study was to evaluate the effect of tamoxifen on bone metabolism and blood cholesterol levels in ovariectomized rats. The study was performed on Wistar rats treated with tamoxifen at 2 and 4 mg/kg/24 h. Total serum cholesterol and low density cholesterol were significantly increased in ovariectomized rats (3.24 mmol/l and 2.06 mmol/l) in comparison with sham operated control (2.68 mmol/l and 1.44 mmol/l) (p < 0.05). Total serum cholesterol and low density cholesterol in tamoxifen-treated rats were significantly decreased in comparision with the values in both sham-operated and ovariectomized control. Bone mineral content (BMC) and bone mineral density (BMD) of femurs of ovariectomized rats (0.32 g and 0.081 g/cm2) decreased significantly compared to sham-operated controls (0.42 g and 0.098 g/cm2) (p < 0.05). Tamoxifen prevented the bone mass reduction induced by ovariectomy. The treatment with tamoxifen at doses of 2 mg/kg/24 h and 4 mg/kg/24 h significantly increased BMC and BMD in comparison with ovariectomized control. The results suggest a beneficial influence of tamoxifen on bone tissue and lipid metabolism.