Association between ABCB1-T1236C polymorphism and drug-resistant epilepsy in Iranian female patients

Background: One third of epileptic patients are resistant to several anti-epileptic drugs (AED). P-glycoprotein (P-gp) is an efflux transporter encoded by ATP-binding cassette subfamily B member 1 (ABCB1) gene that excludes drugs from the cells and plays a significant role in AEDs resistance. Over-expression of P-gp could be a result of polymorphisms in ABCB1 gene. We studied the association of T129C and T1236C single-nucleotide polymorphisms (SNP) of ABCB1 gene with drug-resistant epilepsy in Iranian epileptics. Methods: DNA samples were obtained from 200 healthy controls and 332 epileptic patients, of whom 200 were drug responsive and 132 drug resistant. The frequencies of the genotypes of the two SNP were determined by polymerase chain reaction followed by restriction fragment length polymorphism. Results: No significant association was found between T129C and T1236C genotypes and drug-resistant epilepsy neither in adults nor in children. However, the risk of drug resistance was higher in female patients with 1236CC (P = 0.02) or CT (P = 0.008) genotype than in those with TT genotype. The risk of drug resistance was also higher in patients with symptomatic epilepsies with 1236CC (P = 0.02) or CT (P = 0.004) genotype than in those with TT genotype. The risk of drug resistance was lower in patients with idiopathic epilepsies with 129TT genotype (P = 0.001) than in those with CT genotype. Conclusion: Our results indicate that T1236C polymorphism is associated with drug resistance in Iranian female epileptic patients. Replication studies with large sample sizes are needed to confirm our results. Key Words: ATP-binding cassette subfamily B member 1 (ABCB1), Drug-resistant epilepsy, Single nucleotide polymorphism     

普洱茶对非酒精性脂肪肝大鼠肠道脂肪吸收及粘膜屏障的干预研究

研究了普洱茶调控非酒精性脂肪肝大鼠肠道对长链脂肪酸的吸收,并探讨了其可能机制。将36只SD大鼠随机分成正常对照组、脂肪肝模型组和普洱茶干预组,每组12只。实验第8周末处死所有大鼠,测定大鼠体质量、肝指数及血清血脂水平;采用定量PCR测定大鼠肠道黏膜脂质吸收相关蛋白细胞分化抗原36(Cluster of differentiation 36,CD36)、紧密连接相关蛋白如闭锁蛋白(Occludin)、紧密连接蛋白(Zonula occludens 1,ZO-1)和肿瘤坏死因子α(Tumor necrosis factor-α,TNF-α)基因表达水平。研究结果表明,与模型组相比,普洱茶组大鼠体质量和血清LDL-C水平分别下降了16.12%和42.59%;此外,普洱茶组大鼠小肠组织CD36、TNF-α表达水平明显降低,而Occludin、ZO-1表达水平明显升高。研究发现,普洱茶对NAFLD大鼠肠道长链脂肪酸吸收及肠道紧密连接蛋白有一定程度的调控作用,尤其是对NAFLD早期发生发展中游离脂肪酸过度沉积的"第一次打击"有防治价值。     

茶叶中EGCG对非酒精性脂肪肝大鼠的调脂保肝作用研究

非酒精性脂肪肝是以肝实质细胞发生脂肪堆积和脂肪变性为主要特征,并伴随机体脂质代谢紊乱的一种获得性代谢疾病。以高脂饲料喂养大鼠,建立非酒精性脂肪肝大鼠模型;以低、中、高剂量（10、50、100 mg·kg^-1）表没食子儿茶素没食子酸酯（EGCG）分别灌胃模型大鼠,探讨茶叶中EGCG对非酒精性脂肪肝大鼠的调脂保肝作用。结果表明,与模型组相比,EGCG能显著降低血清中甘油三酯（TG）、总胆固醇（TC）和低密度脂蛋白-胆固醇（LDL-C）含量,降低丙氨酸氨基转移酶（ALT）和天冬氨酸转氨酶（AST）活性水平,提高高密度脂蛋白-胆固醇（HDL-C）的含量,改善大鼠肝脏氧化应激状态。此外,肝脏病理切片显示,EGCG能减少肝细胞中脂滴的形成,同时脂质代谢相关基因表达量分析显示,EGCG能调理肝脏的脂质代谢。综合以上实验结果表明,EGCG能显著改善非酒精性脂肪肝大鼠的脂质代谢紊乱和脂肪性肝损伤。     

Frequency of Efficient Circulating Follicular Helper T Cells Correlates with Dyslipidemia and WBC Count in Atherosclerosis

Background:The significance of cTfh cells and their subsets in atherosclerosis is not well understood. We measured the frequency of cTfh subsets in patients with different degrees of stenosis using flow-cytometry. Methods:Participants included high (≥50%; n = 12) and low (<50%; n = 12) stenosis groups, as well as healthy controls (n = 6). Results: The frequency of CCR7^loPD-1^hiefficient-cTfh was significantly higher in patients with high stenosis compared to healthy controls (p = 0.003) and correlated with LDL (p = 0.043), cholesterol (p = 0.043), triglyceride (p = 0.019), neutrophil count (p = 0.032), platelet count (p = 0.024), NLR (p = 0.046), and PLR (p = 0.025) in high stenosis group. The frequency of CCR7^hiPD-1^lo quiescent-cTfh was higher in healthy controls compared to the high-stenosis group (p = 0.001) and positively correlated with HDL (p = 0.046). The frequency of efficient-cTfh cells was correlated with platelet count (p = 0.043), NLR (p = 0.036), and PLR (p P = 0.035) in low-stenosis group, while that of quiescent-cTfh cells was negatively correlated with LDL (p = 0.034), cholesterol (p = 0.047), platelet count (p = 0.032), and PLR (p = 0.041). Conclusion:High percentages of cTfh and efficient-cTfh cells in patients with advanced atherosclerosis and their correlation with dyslipidemia and WBC counts suggests an ongoing cTfh subset deviation, towards efficient phenotype in the milieu of inflammation and altered lipid profile. Efficient cTfh cells have an effector phenotype and could in turn contribute to atherosclerosis progression. Key Words: Atherosclerosis, Blood Platelets, Neutrophils, Dyslipidemias     

Somatosensory evoked potential for detection of subclinical neuropathy in Egyptian children with acute lymphoblastic leukaemia

To evaluate neurological changes developing during paediatric Acute Lymphoblastic Leukaemia (ALL) therapy clinically and through electrophysiological Study of Somatosensory Evoked Potentials (SSEPs) changes in different phases of therapy. Thirty five-ALL patients with age range from 3-14 years were included compared to 30 healthy controls. History, neurological examination, complete blood counts, cytological examination of bone marrow aspirate and cerebrospinal fluid with Measurement of Serum Methotrexate (MTX) were done. The SSEPs were performed and patients subjected to another SSEP with measurement of serum MTX level before and 10 days after intra-thecal injection (IMTX). Clinical neurological findings in patients after induction were depressed deep tendon reflexes (43.3%), hypotonia (28.6%), lost pain sensation (28.6%), muscle weakness (17.1%) and movement disorders (17.1%). Percentage of delayed SSEPs after induction were at levels of brachial plexus (28.6%), spinal cord (68.6%), cortical conduction (31.4%), ERB-N13 Inter Peak Latency (IPL) (74.3%) and N13-N20 IPL (17.1%) in the studied patients. Significant prolonged latency of N13 (p = 0.005), N20 (p = 0.04) and IPL of ERB-N 13 (p = 0.005), N13-N20 (p = 0.01), Inter-Side Difference (ISD) of N13 (p = 0.01), ERB-N13 (p = 0.02) and N13-N20 (p = 0.03) after induction compared to values at diagnosis. Significant positive correlation were found between serum MTX after IMTX with N13-N20 IPL (p = 0.01), N20 ISD (p = 0.03) with significant prolongation in N20 latency, N13-N20 IPL and ISD of N20 compared to values before injection. ALL patients have prolonged latency of SSEPs at cervical cord and cortical levels which increased after IMTX due to axonal injury throughout the cord. SSEPs could be an early diagnostic tool for subclinical neuropathy.     

Prevention of Nonalcoholic Steatohepatitis in Rats by Two Manganese-Salen Complexes

Background: Nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis with inflammation. Investigations have suggested that oxidative stress may play an important role in the progress of NAFLD to NASH. To provide further insights into beneficial effects of antioxidants in NASH prevention, we employed two manganese-superoxide dismutase/catalase mimetics, manganese N,N`-bis(salicyldene) ethylene diamine chloride (EUK-8) and manganese-3-methoxy N,N`-bis(salicyldene)ethylenediamine chloride (EUK-134), as two salen representatives and vitamin C as the standard antioxidant. Methods: Experimental NASH was induced in Male N-Mary rats by feeding a methionine/choline-deficient (MCD) diet to rats for 10 weeks. The rats (n = 5, 30 mg/kg/day) were randomly assigned to receive vitamin C, EUK-8, EUK-134 or vehicle orally. Results: Administration of salens together with the MCD diet reduced the serum aminotransferases, glutathione transferase and alkaline phosphatase, cholesterol, and LDL contents. In addition, the EUK-8 and EUK-134 improved NASH pathological features in liver of MCD-fed rats. Conclusion: EUK-8 and EUK-134 supplementation reduces NASH-induced abnormalities, pointing out that antioxidant strategy could be beneficial for prevention of NASH.Key Words: Fatty liver, Oxidative stress, Antioxidants     

茯砖茶对NAFLD大鼠肠道黏膜屏障及肝损伤的保护作用研究

为探讨茯砖茶对高脂诱导的非酒精性脂肪肝病（Non-alcoholic fatty liver disease,NAFLD）大鼠肠黏膜屏障及肝损伤的保护作用,将SD雄性大鼠随机分为正常组、NAFLD组、茯砖茶低、高剂量组,每组8只。通过分析大鼠的采食量、体重变化、血脂指标、肝脏指标及病理切片来评估NAFLD大鼠模型的构建情况及茯砖茶的干预作用。通过分析空肠与结肠病理及PAS染色切片、绒毛高度/隐窝深度值（V/C值）、血清二胺氧化酶（DAO）和脂多糖（LPS）活力评估肠道完整性和通透性;通过分析空肠上皮间淋巴细胞（JIL）数量和血清肿瘤坏死因子（TNF-α）活力评估肠道相关炎症。结果表明,茯砖茶能减少NAFLD大鼠的采食量和体重,降低血脂水平,减少血清中谷草转氨酶（AST）和谷丙转氨酶（ALT）活力,并抑制肝脏的脂质聚集和炎细胞浸润。茯砖茶还降低了血清炎症因子TNF-α和血清LPS的水平,并使血清DAO活力上升。同时,茯砖茶抑制了NAFLD大鼠空肠和结肠绒毛中发生的炎细胞浸润现象,减少了空肠绒毛脱落、断裂、稀疏和紊乱现象,增加了空肠绒毛V/C值,降低了空肠上皮间淋巴细胞数量,增加了空肠和结肠的杯状细胞数量。这些结果说明,茯砖茶能够有效的改善高脂饮食诱导的肠道黏膜屏障及肝损伤,起到防治NAFLD的作用。     

Update on Non-Alcoholic Fatty Liver Disease-Associated Single Nucleotide Polymorphisms and Their Involvement in Liver Steatosis,Inflammation, and Fibrosis: A Narrative Review

Genetic factors are involved in the development, progression, and severity of NAFLD. Polymorphisms in genes regulating liver functions may increase liver susceptibility to NAFLD. Therefore, we conducted this literature study to present recent findings on NAFLD-associated polymorphisms from published articles in PubMed from 2016 to 2021. From 69 selected research articles, 20 genes and 34 SNPs were reported to be associated with NAFLD. These mutated genes affect NAFLD by promoting liver steatosis (PNPLA3, MBOAT7, TM2SF6, PTPRD, FNDC5, IL-1B, PPARGC1A, UCP2, TCF7L2, SAMM50, IL-6, AGTR1, and NNMT), inflammation (PNPLA3, TNF-α, AGTR1, IL-17A, IL-1B, PTPRD, and GATAD2A), and fibrosis (IL-1B, PNPLA3, MBOAT7, TCF7L2, GATAD2A, IL-6, NNMT, UCP, AGTR1, and TM2SF6). The identification of these genetic factors helps to better understand the pathogenesis pathways of NAFLDKey Words: Fibrosis, Inflammation, Non-alcoholic fatty liver disease, Polymorphism     

The revised international autoimmune hepatitis score in chronic liver diseases including autoimmune hepatitis/overlap syndromes and autoimmune hepatitis with concurrent other liver disorders

Background

We conducted a study in order to determine the usefulness and diagnostic value of International Autoimmune Hepatitis Group (IAHG) score in non-autoimmune hepatitis (AIH) hepatic disorders as well as in AIH/overlap syndromes and in cases with coexistence of AIH and other liver diseases.

Methods

We applied the IAHG score in 423 patients with liver diseases excluding patients with AIH, AIH/overlap syndromes and AIH with concurrent other liver disease namely, patients with chronic hepatitis B (n = 109), chronic hepatitis C (n = 95), chronic hepatitis D (n = 4), alchoholic liver disease (n = 28), non-alcoholic fatty liver disease (n = 55), autoimmune cholestatic liver diseases (n = 77), liver disorders of undefined origin (n = 32) and with miscellaneous hepatic disorders (n = 23). 24 patients with AIH associated with any kind of liver disorder including 10 patients with AIH/overlap syndromes and 14 AIH with concurrent other liver disease were also investigated. 43 patients with AIH consisted the control group.

Results

The specificity of the score was 98.1% while the sensitivity in unmasking AIH in patients with either AIH/overlap syndromes or AIH with concurrent other liver diseases was only 50% and 78.6%. In the binary logistic regression model, the presence of other autoimmune diseases (p < 0.001), the total histological score (p < 0.001) and positivity for autoantibodies (p < 0.05) were identified as independent predictors for the presnce of AIH/ovea syndromes o AI with concurren other liver diseass.

Conclusion

The IAHG scoring system has very good specificity for excluding AIH in patients with chronic liver diseases but not that sensitivity in order to unmask AIH/overlap syndromes or AIH with concurrent other liver diseases. The presence of other autoimmune diseases or autoantibody markers in the absence of hepatitis viral markers should alarm physicians for the possible presence of AIH either as "pure" AIH or in association with other liver disorders (AIH/overlap syndromes or AIH with concurrent other liver diseases). Under these conditions, liver histology seems essential and it must always be included in the work up of hepatic patients.

     

从肠道菌群改变探讨青砖茶对非酒精性脂肪肝的预防作用

通过肠道菌群改变研究青砖茶(GBT)对小鼠非酒精性脂肪肝(NAFLD)的预防作用。C57BL/6小鼠随机分为5组,即正常对照组(NC),模型对照组(MC),阳性药物对照组(PC)以及青砖茶低剂量组(LD)、高剂量组(HD),高脂饲料喂养小鼠建立NAFLD模型,同时预防性给予低、高剂量青砖茶水提取物和阳性药物血脂康,分别测定小鼠的体重、食物利用率、肝重、肝指数、TC、LDL-C/HDL-C及ALT含量,HE染色和油红O染色观察肝组织病理切片,ELISA检测肝组织IL-1β、IL-18含量变化,16 SrDNAV3-V4区高通量测序分析肠道菌群变化,Spearman相关性分析方法分析菌群与NAFLD表型的相关性。与模型组比较,青砖茶组小鼠体重、食物利用率、肝重、肝指数、血清TC、LDL-C/HDL-C、ALT、肝组织TC、IL-1β、IL-18含量均有显著性降低,肝脏病变程度有所改善;肠道菌群分析及相关性分析显示Bacteroides物种丰度降低,且与NAFLD表型呈正相关,Lactobacillus、Alloprevotella、Saccharibacteria_ge...     

Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS/MAPK Pathway in Mice

Background: Hepatic ischemia reperfusion (IR) is an important issue in complex liver resection and liver transplantation. The aim of the present study was to determine the protective effect of astaxanthin (ASX), an antioxidant, on hepatic IR injury via the reactive oxygen species/mitogen-activated protein kinase (ROS/MAPK) pathway. Methods: Mice were randomized into a sham, IR, ASX or IR + ASX group. The mice received ASX at different doses (30 mg/kg or 60 mg/kg) for 14 days. Serum and tissue samples at 2 h, 8 h and 24 h after abdominal surgery were collected to assess alanine aminotransferase (ALT), aspartate aminotransferase (AST), inflammation factors, ROS, and key proteins in the MAPK family. Results: ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury. Conclusion: Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.     

Mitochondrial DNA Copy Number Variations and Serum Pepsinogen Levels for Risk Assessment in Gastric Cancer

Background:Variations in mtDNA-CN of PBLs, as a potential biomarker for GC screening has currently been subject to controversy. Herein, we have assessed its efficiency in GC screening, in parallel and in combination with sPG I/II ratio, as an established indicator of gastric atrophy. Methods:The study population included GC (n = 53) and non-GC (n = 207) dyspeptic patients. The non-GC group was histologically categorized into CG (n = 104) and NM (n = 103) subgroups. The MtDNA-CN of PBLs was measured by quantitative real-time PCR. The sPG I and II levels and anti-H. pylori serum IgG were measured by ELISA. Results:The mtDNA-CN was found significantly higher in GC vs. non-GC (OR = 3.0; 95% CI = 1.4, 6.4) subjects. Conversely, GC patients had significantly lower sPG I/II ratio than the non-GC (OR = 3.2; CI = 1.4, 7.2) subjects. The combination of these two biomarkers yielded a dramatic amplification of the odds of GC risk in double-positive (high mtDNA-CN-low sPGI/II) subjects, in reference to double-negatives (low mtDNA-CN-high sPGI/II), when assessed against non-GC (OR = 27.1; CI = 5.0, 147.3), CG (OR = 13.1; CI = 2.4, 72.6), or NM (OR = 49.5; CI = 7.9, 311.6) groups. Conclusion:The combination of these two biomarkers, namely mtDNA-CN in PBLs and serum PG I/II ratio, drastically enhanced the efficiency of GC risk assessment, which calls for further validations. Key Words: Biomarkers, DNA copy number variation, Mitochondrial DNA, Stomach neoplasms     

Attenuating Effects of Dieckol on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Decreasing the NLRP3 Inflammasome and Pyroptosis

Nonalcoholic fatty liver disease (NAFLD), which promotes serious health problems, is related to the increase in the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and pyroptosis by a high-fat diet (HFD). Whether dieckol (DK), a component of Ecklonia cava extracts (ECE), attenuated NAFLD in an HFD-induced NAFLD animal model was evaluated. The expression of high mobility group box 1/Toll-like receptor 4/nuclear factor-κB, which initiated the NLRP3 inflammasome, was increased in the liver of HFD-fed animals and significantly decreased with ECE or DK administration. The expression of NLRP3/ASC/caspase-1, which are components of the NLRP3 inflammasome, and the number of pyroptotic cells were increased by HFD and decreased with ECE or DK administration. The accumulation of triglycerides and free fatty acids in the liver was increased by HFD and decreased with ECE or DK administration. The histological NAFLD score was increased by HFD and decreased with ECE or DK administration. The expression of lipogenic genes (FASN, SREBP-2, PPARγ, and FABP4) increased and that of lipolytic genes (PPARα, CPT1A, ATGL, and HSL) was decreased by HFD and attenuated with ECE or DK administration. In conclusion, ECE or DK attenuated NAFLD by decreasing the NLRP3 inflammasome and pyroptosis.     

茶多酚改善胰岛素抵抗的初步研究

研究了茶多酚（Tea Polyphenols,TP）降低肝脏中甘油三酯（Triglyceride, TG）含量从而对2型糖尿病性脂肪肝模型大鼠胰岛素抵抗的改善作用。健康SD大鼠分为6组：健康组、模型组、TP组、二甲双胍组、FL组和FL+TP组。所有大鼠在实验结束时测量体重、血清甘油三酯、肝脏中甘油三酯、空腹血糖、血清胰岛素等指标。TP组和二甲双胍组较模型组空腹血糖、血清胰岛素含量和胰岛素敏感指数下降;FL+TP组、TP组较FL组、模型组肝脏中甘油三酯含量下降。茶多酚可显著降低肝脏中的甘油三酯含量,调节脂代谢紊乱并改善胰岛素抵抗。     

Hypolipidemic Effects of Soy Protein and Isoflavones in the Prevention of Non-Alcoholic Fatty Liver Disease- A Review

Plant Foods for Human Nutrition - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and affects about 25% of the population globally. Obesity and diabetes are the...     

Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRG^TM cell line. We found that LMF-HSFx reduces the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose and hemoglobin A1c in NAFLD patients. For lipid metabolism, LMF-HSFx reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression. Interestingly, it reduces liver fibrosis in NAFLD patients, either. The proinflammatory cytokines interleukin (IL)-6 and interferon-γ are reduced in LMF-HSFx group. In HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis. Additionally, LMF-HSFx modulates SIRI-PGC-1 pathway in HepaRG cells under palmitic acid-induced lipotoxicity environment. Here, we describe that LMF-HSFx ameliorated hepatic steatosis, inflammation, fibrosis and insulin resistance in NAFLD patients. LMF-HSFx may modulate leptin-adiponectin axis in adipocytes and hepatocytes, then regulate lipid and glycogen metabolism, decrease insulin resistance and is against NAFLD.     

Association of Lecithin Cholesterol Acyltransferase rs5923 Polymorphism in Iranian Individuals with Extremely Low High-Density Lipoprotein Cholesterol: Tehran Lipid and Glucose Study

Background:

The serum concentration of high-density lipoprotein cholesterol (HDL-C) is one of the important heritable risk factors for cardiovascular disease and is a target for therapeutic intervention. In this study, we aimed to evaluate the effects of lecithin cholesterol acyltransferase (LCAT) gene polymorphism rs5923 on LCAT enzyme activity and serum HDL-C concentration.

Methods:

The study population was selected from consecutive individuals with HDL-C ≤ 5^th percentile (n = 73) and extremely high HDL-C ≥ 95^th percentile (n = 57) who had participated in the Tehran Lipid and Glucose Study. The rs5923 polymorphism was genotyped using direct sequencing. LCAT activity was measured by fluorometric assay kit, and lipid concentrations were measured using the enzymatic colorimetric method.

Results:

The genotype frequencies were significantly different between the high HDL-C group (CC 94.7%, CT 5.3%) and the low HDL-C group (CC 83.6%, CT 16.4%) (P = 0.048). The T-allele frequencies in subjects with low and high HDL-C were 0.082 and 0.026, respectively (P = 0.16). The association of the single-nucleotide polymorphism rs5923 with low HDL-C was not statistically significant after adjustment for age, sex, and BMI (odd ratio = 2.65, 95% confidence interval = 0.32-21.5, P = 0.36, regression logistic analysis). Also, the effects of LCAT enzyme activity did not depend on the HDL-C level (P = 0.24).

Conclusion:

rs5923 polymorphism is not associated with low HDL-C levels in Iranian population. Key Words: Polymorphism, Single nucleotide, Lipoproteins     

Antidiabetic activity evaluation of glimepiride and Nerium oleander extract on insulin, glucose levels and some liver enzymes activities in experimental diabetic rat model

The present study is aimed to assess the therapeutic potential of sulfonylurea drug glimepiride in comparison with Nerium oleander plant extract on insulin, glucose levels and some liver enzymes activities in streptozotocin-induced diabetic rats. Rats were rendered diabetic by intraperitoneal injection of a single dose of 50 mg kg(-1) body weight streptozotocin. Rats with serum glucose levels > 200 mg dL(-1) were subdivided into three sub-groups: the first sub-group were remained without treatment and considered as diabetics. The second and third subgroups were orally administered 0.1 mg kg(-1) body weight/day glimepiride and 250 mg kg(-1) body weight/day Nerium oleander, respectively for 4 weeks. Streptozotocin-induced diabetic rats showed hypoinsulinemia and hyperglycemia compared to controls. Strong negative correlation (r = -0.8) was found between serum insulin and glucose levels in diabetic rats. This correlation was +0.4 and -0.3 in glimepiride and Nerium olender-treated rats, respectively implying that glimepiride and plant extract improved insulin and glucose levels with the former was more efficient. The activities of serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were significantly increased in streptozotocin-induced diabetic rats compared to controls. Treatment of diabetic rats with glimepiride or Nerium oleander extract also improved liver enzymes activities.