Piperine Improves Experimental Autoimmune Encephalomyelitis (EAE) in Lewis Rats Through its Neuroprotective, Anti-inflammatory, and Antioxidant Effects.

Inflammation, demyelination, glial activation, and oxidative damage are the most pathological hallmarks of multiple sclerosis (MS). Piperine, a main bioactive alkaloid of black pepper, possesses antioxidant, anti-inflammatory, and neuroprotective properties whose therapeutic potential has been less studied in the experimental autoimmune encephalomyelitis (EAE) models. In this study, the efficiency of piperine on progression of EAE model and myelin repair mechanisms was investigated. EAE was induced in female Lewis rats and piperine and its vehicle were daily administrated intraperitoneally from day 8 to 29 post immunization. We found that piperine alleviated neurological deficits and EAE disease progression. Luxol fast blue and H&E staining and immunostaining of lumbar spinal cord cross sections confirmed that piperine significantly reduced the extent of demyelination, inflammation, immune cell infiltration, microglia, and astrocyte activation. Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-inflammatory cytokines (TNF-α, IL-1ß) and iNOS and enhanced IL-10, Nrf2, HO-1, and MBP expressions. Piperine supplementation also enhanced the total antioxidant capacity (FRAP) and reduced the level of oxidative stress marker (MDA) in the CNS of EAE rats. Finally, we found that piperine has anti-apoptotic and neuroprotective effect in EAE through reducing caspase-3 (apoptosis marker) and enhancing BDNF and NeuN expressing cells. This study strongly indicates that piperine has a beneficial effect on the EAE progression and could be considered as a potential therapeutic target for MS treatment. Upcoming clinical trials will provide a deeper understanding of piperine's role for the treatment of the MS.

Arbutin attenuates nephrotoxicity induced by gentamicin.

OBJECTIVE: In this study, the impact of arbutin was examined in a gentamicin (GM)-induced nephrotoxicity model. MATERIALS AND METHODS: Forty adult male Wistar rats were randomly assigned to five groups including control group; GM group, and three groups of GM+arbutin (25, 50 and 75 mg/kg). One day after the last injection of GM, creatinine, urea, carbonyl, thiobarbituric acid-reacting substance (TBARs), ferric reducing antioxidant power (FRAP) and 8-hydroxyguanosine levels were assessed in serum samples. Left and right kidneys were used for biochemical assays and histological evaluation, respectively. RESULTS: Our data showed that the FRAP level (p<0.05), urea (p<0.001), creatinine (p<0.001), and 8-hydroxyguanosine (p<0.001) levels of serum samples, were increased in GM-treated rats compared to the controls. The serum levels of TBARS (p<0.001) and carbonyl increased in serum and renal tissue (p<0.001) of GM-treated animals. Conversely, arbutin attenuated serum creatinine, urea and 8-hydroxyguanosine, and TBARS (p<0.001). Administration of arbutin significantly decreased carbonyl levels in serum and renal tissue samples (p<0.001). Furthermore, the levels of FRAP increased in the serum (p<0.01) and renal tissue samples (p<0.001) of arbutin-treated animals. Histological staining showed that arbutin significantly inhibits kidney damages. CONCLUSION: Our data suggest that arbutin attenuates GM-induced nephrotoxicity through its free radicals-scavenging activity.

ABCA1 and metabolic syndrome; a review of the ABCA1 role in HDL-VLDL production, insulin-glucose homeostasis, inflammation and obesity.

ATP-binding cassette transporter A1 (ABCA1) is an integral cell-membrane protein that mediates the rate-limiting step of high density lipoprotein (HDL) biogenesis and suppression of inflammation by triggering a number of signaling pathways via interacting with an apolipoprotein acceptor. The hepatic ABCA1 is involved in regulation of very low density lipoprotein (VLDL) production by affecting the apolipoprotein B trafficking and lipidation of VLDL particles. This protein is involved in protecting the function of pancreatic ß-cells and insulin secretion by cholesterol homeostasis. Adipose tissue lipolysis is associated with ABCA1 activity. This transporter is involved in controlling obesity and insulin sensitivity by regulating triglyceride (TG) lipolysis and influencing on adiponectin, visfatin, leptin, and GLUT4 genes expression. The ABCA1 of skeletal muscle cells play a role in increasing the glucose uptake by enhancing the Akt phosphorylation and transferring GLUT4 to the plasma membrane. Abnormal status of ABCA1-regulated phenotypes is observed in metabolic syndrome. This syndrome is associated with the occurrence of many diseases. This review is a summary of the role of ABCA1 in HDL and VLDL production, homeostasis of insulin and glucose, suppression of inflammation and obesity controlling to provide a better insight into the association of this protein with metabolic syndrome.

The ENPP1 K121Q polymorphism modulates developing of bone disorders in type 2 diabetes: A cross sectional study.

BACKGROUND: Osteoporosis and osteopenia are common diseases in every population. Type 2 diabetes mellitus (T2DM) can lead to the development of various complications, such as bone disorders especially among elderly individuals. Studies suggested that ectonucleotide pyrophosphatase/phosphodiesterase1 (ENPP1) is contributed in insulin resistance and also the inhibition of bone mineralization. In this study, association of K121Q (rs1044498) polymorphism of the ENPP1 gene with T2DM and bone disorders is evaluated. METHODS: Four-hundred-and-ninety females who were classified based on bone mineral density (BMD) at lumbar spine and femur were included in this study. In addition, participants were classified according to their diabetes status. K121Q polymorphism was evaluated by the PCR-PFLF technique. One-way ANOVA was used for comparison of various analyzed factors in diseases subgroups and K121Q genotypes. Association of K121Q polymorphism with diabetes and bone disorders was evaluated by logistic regression. RESULTS: Significant association was observed between K121Q polymorphism with osteoporosis and osteopenia (p=0.041, p=0.029, respectively), but a similar pattern was not observed in T2DM status (p=0.723). Moreover, in diabetic patients, K121Q polymorphism showed a better prediction potential for the development of bone disorders in comparison to non-diabetic subjects (p=0.018; OR=4.63, p=0.540; OR=1.31). There were no significant differences between K121Q genotypes with FBS, Ca, P, vitamin D, PTH and BMD status. CONCLUSIONS: The present study implies that K121Q polymorphism of ENPP1 gene is able to modulate the development of bone disorders in T2DM. Therefore in diabetic patients screening of this polymorphism is suggested for the monitoring of these persons.

Association of ATP-Binding Cassette Transporter A1 (ABCA1)-565 C/T Gene Polymorphism with Hypoalphalipoproteinemia and Serum Lipids, IL-6 and CRP Levels.

BACKGROUND: ATP-binding cassette transporter A1 (ABCA1) is a membrane integral protein which plays a vital role in High Density Lipoprotein (HDL) metabolism and exerts a protective effect against Hypoalphalipoproteinemia (HA) by mediation of rate-limiting step in HDL biogenesis. In addition, this protein possesses anti-inflammatory effects by inhibiting the production of some inflammatory cytokines in macrophages. This study investigated the association of ABCA1-565 C/T gene polymorphism with HA and serum lipids, IL-6 and CRP levels. METHODS: A population which consisted of 101 HA and 95 normal subjects were genotyped for ABCA1-565C/T polymorphism by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The serum concentrations of lipids, IL-6 and high sensitive-CRP (hs-CRP) were measured by the relevant methods. RESULTS: The frequency of T allele was significantly higher in the HA group than the controls (31.7 vs. 19.5%, p=0.002). Thus, carriers of the T allele (CT and TT genotypes) had a higher risk for HA (p=0.016, OR=2.04, 95% CI=1.14-3.63). T allele carriers demonstrated decreased HDL-C and increased triglyceride, IL-6 and CRP levels than those with the CC genotype. CONCLUSION: This study suggests that the-565 C/T polymorphism of ABCA1 gene is associated with an increased risk of HA, decreased HDL-C and increased TG, IL-6 and CRP.

Pre and post radiotherapy serum oxidant/antioxidant status in breast cancer patients: Impact of age, BMI and clinical stage of the disease.

AIM: In this study the effects of radiation therapy (RT) on serum oxidant/antioxidant status in breast cancer patients and the impact of age, BMI and clinical stage of the disease on the aforementioned variables were investigated. BACKGROUND: RT that is used for cancer treatment is dependent on the production of reactive oxygen species. MATERIALS AND METHODS: Eighty patients with breast cancer participated in this study and received RT at a dose of 50 Gy for 5 weeks. Blood samples were obtained in one day before and after the end of RT. Serum status of malondialdehyde (MDA), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were analyzed by spectrophotometry or ELISA and selenium (Se) level were analyzed by atomic absorption spectrometry. Paired t-test was used for comparing pre and post radiotherapy data. RESULTS: Before and after the radiotherapy, a significant increase in MDA level was observed, while a significant decrease in GPx activity, SOD, TAS and Se levels were found (p < 0.05). The level of the CAT enzyme had no significant changes (p = 0.568). The results showed some changes in the status of TAS, SOD and GPx which are associated with age, BMI and clinical stage of the disease. CONCLUSION: It seems that RT would have the potential to cause variations in the status of antioxidant/oxidant system. Although, some changes in variables were observed by sub-classification of the age, BMI and the disease stage, but it seems that these changes are not necessarily dependent to them.

Vitamin D Receptor Poly(A) Microsatellite Polymorphism and 25-Hydroxyvitamin D Serum Levels: Association with Susceptibility to Breast Cancer.

PURPOSE: According to previous studies, vitamin D exhibits protective effects against breast cancer via the vitamin D receptor (VDR). There is growing evidence that breast cancer incidence is associated with various polymorphisms of the VDR gene. This study investigates the association of VDR poly(A) microsatellite variants with 25-hydroxyvitamin D (25(OH)D) serum levels and breast cancer risk. METHODS: Polymorphism analysis was performed on a total of 261 blood samples, which were collected from 134 women with breast cancer and 127 controls. Single strand conformation polymorphism was assessed by polymerase chain reaction in combination with sequencing to detect poly(A) lengths for each sample. The vitamin D levels of samples were determined by electrochemiluminescence. RESULTS: The poly(A) variant L allele frequency was significantly higher in cancer patients than in controls (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.16-2.57; p=0.006). Thus, carriers of the L allele (LS and LL genotypes) have a higher risk for breast cancer (OR, 1.86; 95% CI, 1.13-3.05; p=0.013). A larger increase in the risk for breast cancer was found in individuals with the L carrier genotype and lowered 25(OH)D levels. CONCLUSION: The results primarily suggest that VDR gene polymorphism in the poly(A) microsatellite is associated with 25(OH)D levels and that it can affect the breast cancer risk in the female population from northern Iran.

Dyshomeostasis of Serum Oxidant/Antioxidant Status and Copper, Zinc, and Selenium Levels in Elderly Physically Disabled Persons: an AHAP-Based Study.

The percentage of elderly persons is rapidly growing. Physical disability is one of the main age-related diseases which affect life quality. There are some studies that suggest the oxidative stress and trace elements are involved in physical disability in elderly persons, but the results are inconclusive. Therefore, the aim of this study was to investigate the status of aforementioned parameters in elderly physically disabled patients vs. healthy ones. According to the Katz questionnaire form, 44 subjects with physical disability and 66 age-gender-matched healthy subjects were selected from Amirkola Health and Aging Project (AHAP). The results indicated that patient group had lower serum Zn, Se, and total antioxidant levels than the control group (p < 0.001), whereas serum total oxidant level and Cu to Zn ratio (CZr) were higher in control group than in healthy one (p < 0.001). A positive correlation was found between Zn, Se, total antioxidant, and bone mineral density of femur (BMD.F) with activities of daily living (ADL) score (p < 0.01); meanwhile, a negative correlation between CZr and total oxidant with ADL score was observed (p < 0.01). Serum total oxidant level and CZr index had the highest area under the curve in receiver operating characteristic (ROC) analysis among the included parameters for discrimination of physically disabled patients than the normal ones. Decrease in serum Zn and Se levels, low BMD, and increase in CZr and oxidative stress were observed in physically disabled patients. It seems that CZr is more reliable parameter than the others to discriminate the physically disabled patients than the healthy persons.

Effect of zinc-deficient nutrition on craniofacial bone growth in rats.

BACKGROUND: Zinc (Zn) is an essential nutrient that is required in humans and animals for the growth, development, and maintenance of healthy bones. The aim of this study is to investigate the effects of zinc-deficient nutrition on the dental, mandibular, maxillary, and cranial dimensions of rats. MATERIALS AND METHODS: This experimental study was carried out on 14 male Wistar rats. The rats were randomly divided into two groups. Group I rats were fed with a Zn-deficient (ZD) diet, and Group II rats with a Zn-containing (ZC) diet. All the rats on the experimental diet were killed at the end of the fourth week and their blood samples were taken. The serum Zn levels were measured by an atomic absorption spectrophotometer. Radiographic assessment of the jaw bone density was done at the end of the study. Subsequently, the final measurements were made on the dry skulls, the mandibles, and teeth in both the groups. Statistical evaluation was performed by the student's t-test and repeated measures analysis. The difference between the groups was considered statistically significant if P < 0.05. RESULTS: The ZD group showed a significantly lower value in body weight (P < 0.05), serum level of zinc (P < 0.0001), and radiographic bone density of the mandible (P = 0.02). With regard to the craniofacial parameters, a significant difference was observed only in the length of the clinical crowns of the teeth (L13), which were longer in group II as compared to group I (P = 0.03). CONCLUSION: This study confirmed that changes in zinc intake could not affect the growth of craniofacial structures. Also, it might change the radiographic bone density of the mandible.

Effect of zinc-deficient diet on oral tissues and periodontal indices in rats.

Zinc (Zn) as a nutritional factor affects the health of the oral tissues. This study was done for the evaluation of the effects of zinc deficiency on the oral tissues of rats. The study was carried out on 14 male Wistar rats, cessation of lactation on the 24(th) day after birth. The rats were randomly divided into two groups. Zinc deficient (ZD) diet was used for one group and another group was fed with a zinc-containing (ZC) diet. The alterations of the oral tissues in both groups were evaluated clinically after four weeks. Also the gingival index and periodontal pocket depth were recorded. The measurement of serum zinc level was done by atomic absorption spectrophotometry. The microscopic slides of oral tissue specimen were evaluated quantitatively. The serum zinc level of the ZD rats was lower than the ZC group (p< 0.001). According clinical findings, the gingival index was lower in ZC rat (p=0.001), but there was no significant difference regarding the periodontal pocket depth between two groups (p=0.07). Aphthous ulcer was observed in ZD rats on the floor of the mouth. There was no significant difference regarding the epithelial and keratin thickening between two groups. This study indicated that oral and periodontal health was better in ZC rats than in ZD rats. Aphthous lesions were more prominent in ZD rats. This study confirmed that zinc deficiency may endanger oral and periodo ntal structures.

The age effect on the association between the scavenger receptor class B type I (SR-BI) polymorphism and HDL-C level: Tehran Lipid and Glucose Study.

INTRODUCTION: The scavenger receptor class B type I (SR-BI) is a key component in the reverse cholesterol transportation. The aim of this study was to assess the association between exon1 (G → A) polymorphism of SR-BI gene and lipid profiles among the Tehran Lipid and Glucose Study (TLGS) population. MATERIALS AND METHODS: This cross-sectional study included 774 adults (322 males and 452 females) aged 20-70 years who were randomly selected from among TLGS population. Anthropometrical and biochemical variables for participants were measured. Selected SR-BI gene polymorphism was determined with restriction fragment length polymorphism, via Alu restriction enzyme. RESULTS: Minor allele frequency for SR-BI polymorphism in the selected population was 0.159. Allele frequencies were in conformity with Hardy-Weinberg equilibrium. Association between (G → A) SR-BI polymorphism and high density lipoprotein cholesterol (HDL-C) and HDL3 was significant only after adjustment for age as a potential covariate (p = 0.046, 0.041, respectively); however, the results did not improve after adjustment for sex. DISCUSSION: The result of this study confirms the role of age as a potential confounder which could modify the association between the SR-BI single nucleotide polymorphism and HDL-C level.

Association of two common polymorphisms of apolipoprotein A5 gene with metabolic syndrome indicators in a North Iranian population, a cross-sectional study.

BACKGROUND: Metabolic syndrome is an obesity dependent disorder with a worldwide high prevalence. Regarding the high prevalence of Metabolic syndrome in Iran we analyzed the influence of -1131T>C (rs662799) and c.56C>G (S19W, rs3135506) polymorphisms of the novel apolipoprotein gene, ApoA5, on some Metabolic Syndrome indicators in population from north of Iran. METHODS: 199 volunteers from Babol city-Iran were divided in two groups of low (N = 99, TG ≤ 103 mg/dl) and high (N = 100, TG ≥ 150 mg/dl) serum levels of Triglycerides (TG). We amplified the gene fragments containing -1131T>C and c.56C>G polymorphisms by PCR method and revealed the polymorphisms by RFLP analysis. RESULTS: We found a significant association (p = 0.016, Independent t-test) between high levels of TG and -1131T>C polymorphism but not between this polymorphism and serum HDL-C concentrations. Carriers of the C allele had a 1.97 times higher odds ratio to be in the high-TG group than those of the TT genotype (95%, CI = 1.05-3.68). We observed no association between -1131T>C polymorphism with either Waist-to-Hip Ratio (WHR) or Body-Mass-Index (BMI). In the case of c.56C>G polymorphism, although it showed a significant relationship with WHR (p = 0/040, Independent t-test), but failed to correlate with either levels of TG (p = 0.594) or HDL-C (p = 0.640) in serum. CONCLUSION: Our study confirms that ApoA5 gene polymorphisms, -1131T>C and c.56C>G are associated with the two criteria of Metabolic Syndrome, TG and WHR, respectively.

Effect of Urtica dioica Leaf Alcoholic and Aqueous Extracts on the Number and the Diameter of the Islets in Diabetic Rats.

Urtica dioica has been known as a plant that decreases blood glucose. Despite the importance of this plant in herbal medicine, relatively little research has been down on effects of this plant on islets yet. The objective of the current study was to evaluate the effect of dried Urtica dioica leaf alcoholic and aqueous extracts on the number and the diameter of the islets and histological parameters in streptozocin-induced diabetic rats. Six rats were used in each group. Group I: Normal rats were administered saline daily for 8 weeks. Group II: Diabetic rats were administered streptozotocin, 50 mg/kg of body weight; Group III: Diabetic rats were administered dried Urtica dioica leaf aqueous extracts for 8 weeks; Group IV: Diabetic rats were administered dried Urtica dioica leaf alcoholic extracts for 8 weeks. The animals, groups of diabetic and normal, were sacrificed by ether anaesthesia. Whole pancreas was dissected. The tissue samples were formalin fixed and paraffin embedded for microscopic examination. Histologic examination and grading were carried out on hematoxylin-eosin stained sections. The effects of administration of dried Urtica dioica leaf alcoholic and aqueous extracts to diabetic rats were determined by histopathologic examination. The pancreas from control rats showed normal pancreatic islets histoarchitecture. Our results also, indicate that the pancreas from diabetic rats show injury of pancreas tissue while the pancreas from diabetic rats treated with dried Urtica dioica leaf alcoholic and aqueous extracts show slight to moderate rearrangement of islets. According to our findings, dried Urtica dioica leaf alcoholic and aqueous extracts can cause a suitable repair of pancreatic tissue in streptozocin-induced diabetic experimental model.

Haplotype analysis of Apo AI-CIII-AIV gene cluster and lipids level: Tehran Lipid and Glucose Study.

Iranian populations show an increased tendency for abnormal lipid levels and high risk of Coronary artery disease. Considering the important role played by the ApoAI-CIII-AIV gene cluster in the regulation of the level and metabolism of lipids, this study aimed at elucidating the association between five single nucleotide polymorphisms on the Apo11q cluster gene and lipid levels. A cross-sectional study of 823 subjects (340 males and 483 females) from the Tehran lipid and glucose study (TLGS) was conducted. Levels of TG, Chol, HDL-C, Apo AI, Apo AIV, Apo B, and Apo CIII were measured, and the selected segments of the APOAI-CIII-AIV gene cluster were amplified by PCR and the polymorphisms were revealed by RFLP using restriction enzymes. The allele frequencies for each SNP between males and females were not significantly different. The distribution of Genotypes and alleles was in Hardy-Weinberg equilibrium except for Apo AI (+83C>T). The results showed a significant association between TG, HDL-C, HDL(2), Apo AI, and Apo B levels and the presence of some alleles in the polymorphisms studied. After haplotype analysis not only did the association between these variables and SNPs remain but also levels of Chol and LDL-C were added. This study demonstrates that the level of lipids such as TG, HDL-C, HDL(2), Apo AI, and Apo B, maybe regulated partly by genetic factors and their haplotype within the Apo11q gene cluster.

Effects of Teucrium Polium Aerial Parts extract on oral glucose tolerance tests and pancreas histopathology in Streptozocin-induced diabetic rats.

Teucrium polium can reduce serum glucose. There are few reports in the literature related to this subject and the resolution of this mechanism requires further experiments. The aim of the present study was to evaluate the effects of Teucrium polium aerial parts extracts on oral glucose tolerance tests and pancreas histology in streptozocin-induced diabetic rats. In order to prepare the aqueous concentrate, aerial parts extract was dissolved in distilled water and was boiled for 30 minutes. For the preparation of ethanolic solution, powder was dissolved in ethanol and mixed by a shaker. Diabetic rats were induced with single IP injection of streptozotocin (STZ) at a dose of 50 mg/kg body weight dissolved in normal saline just before use to the 16 hr fast rats. Both groups, diabetic and normal were sacrificed by ether anesthesia. The tissue samples were formalin fixed and paraffin embedded for microscopic examination in accordance with routine laboratory procedures. Blood was collected from the tail vein of the rats. Serum glucose levels were then measured by commercial kits by using a glucose oxidized method. There were no biochemical abnormalities or histological changes in the pancreas of control rats. Post treatment of Teucrium polium aerial parts extract reduced the severity of streptozotocin diabetic pancreases. Our histopathological investigation along with the biochemical evaluations showed a significant effect on histological changes in the pancreas of induced diabetic rats upon Teucrium polium aerial parts extract treatment (P<0.05).