Apoptosis Induction with Enhancement of BAX/BCL2 Gene Expression Ratio via Combination Therapy in HT29 Colon Cancer Cells

Background and Aim: Combination therapy is one of the new strategies that minimize resistance to chemotherapy and reduces drug toxicity. Here, we investigated the effect of combination therapy with 5-Fluorouracil and Gamma Tocopherol on cell survival and BAX/BCL2 gene expression ratio in HT29 colon cancer cells. Methods: The proliferation of cancer cells was determined via colony formation assay. BAX/BCL2 ratio was evaluated after incubation with concentrations of 5-Fluorouracil and Gamma Tocopherol via real-time-PCR. Results: The average number of colonies in the cells treated with 5-Fluorouracil, Gamma Tocopherol and their combination of them was 63±4, 78±3, and 28±2, respectively which significantly decreased in the combination group. In contrast with the control group, the BAX/BCL2 ratio remarkably increased when the cell underwent combinational treatment (p<0.05). Conclusion: 5-Fluorouracil and Gamma Tocopherol reduced HT 29 cell proliferation. Our results suggest that combination therapy with 5- Fluorouracil and Gamma Tocopherol can be considered as a strategy for induction of apoptosis via increasing the BAX/BCL2 ratio. *Corresponding Author: Nadereh Rashtchizadeh; Email: [email protected] Please cite this article as: Bazzaz R, Yaghmaei P, Dastmalchi S, Rashtchizadeh N. Apoptosis Induction with Enhancement of BAX/BCL2 Gene Expression Ratio via Combination Therapy in HT29 Colon Cancer Cells. Arch Med Lab Sci. 2020;6:1-7 (e21). https://doi.org/10.22037/amls.v6.3348

Effects of curzerene and Smyrnium cordifolium Boiss. extract on addiction withdrawal syndrome in mice

Introduction: The purpose of this study was evaluating the effect of Smyrnium cordifolium extract (SCE) and curzerene (Cur) on withdrawal syndrome in mice compared with clonidine. Methods: High-performance liquid chromatography (HPLC) was used to determine the active ingredients of S. cordifolium. To evaluate the effects of SCE and Cur, 64 mice were divided into 8 equal groups. Groups 1, 2 and 3 were treated Cur (0.03, 0.06, 0.12 mg/kg, respectively). Groups 4, 5 and 6 were treated with SCE (100, 200, 300 mg/kg, respectively). The seventh group received just morphine. Group 8 received morphine and clonidine (0.2 mg/kg). Results: The results of this study showed that Cur was the most important ingredient in the extract of the plant, and the hydroalcoholic extract yield of S. cordifolium was 17.55% (w/w). The dose of 100 mg/kg of extract (SCE100) and 0.03 mg/kg curzerene (Cur1) (P < 0.05), dose of 200 mg/kg of extract (SCE200) and dose of 0.06 mg/kg curzerene (Cur2), (P < 0.01), dose of 300 mg/kg of extract (SCE300) and dose of 0.12 mg/kg of curzerene (Cur3) (P < 0.001) decreased the symptoms compared to clonidine. Doses higher than 300 mg/kg of extract and 0.12 mg/kg of Cur had fatal effects. All doses of SCE and Cur in comparison with the control group at significant level (P < 0.001) reduced the number of jumping, rearing and teeth chattering in morphine-dependent mice. Conclusion: The findings suggest that SCE and Cur are capable of reducing the symptoms of withdrawal syndrome and their effectiveness may be more than clonidine in reducing the addiction withdrawal syndrome, which may have human therapeutic potential

Thymoquinone recovers learning function in a rat model of Alzheimer’s disease

Objective: Alzheimer's disease is a neurodegenerative disorder characterized by accumulation of amyloid beta in the hippocampus. In recent decades, herbal medicine has been widely used to treat many neurodegenerative disorders,as in comparison to conventional drugs, herbal remedies exert minimal side effects. Here, the effects of thymoquinone, as the main active component of Nigella sativa, on passive avoidance memory in rat model of Alzheimer’s disease, were evaluated. Materials and Methods: Hippocampal injection of amyloid beta (Aβ) was used to induce Alzheimer’s disease in male Wistar rats, followed by intra peritoneal administrations of 5 and 10 mg/kg thymoquinone on a daily basis for 4 weeks. Animals were subjected to fear learning behavior in passive avoidance test and histopathological analysis of the hippocampus was done. Shuttle box test was used to evaluate the condition studying memory. Thioflavin-S and Hematoxylin and Eosine staining were done to confirm Aβ plaque formation and to evaluate the effect of thymoquinone on the pyramidal cells in the hippocampal CA1 region. Results: Amyloid beta caused cognitive dysfunction reflected by increasing initial and step-through latency along with plaque formation and degeneration of pyramidal cells in the hippocampus. Thymoquinone administration ameliorated this effect by significant reductions in plaque formation in CA1 region of the hippocampus and increased latency time. It also increased the number of surviving neurons in the hippocampus. Conclusion: It seems that thymoquinone improved learning function in a rat model of Alzheimer’s disease. Thus, thymoquinone could be possibly used as an anti-neurodegenerative agent for protecting hippocampal neurons against neurotoxic effects of Aβ in patients with Alzheimer’s disease

Effect of inulin supplementation in male mice fed with high fat diet on biochemical profile and α-amylase gene expression

Purpose: To evaluate the preventive and therapeutic effects of inulin  supplementation in Naval Medical Research Institute (NMRI) male mice fed with high fat diet.Methods: NMRI male mice (n = 36) were divided into three groups. Control (C1), obese (O1) and experimental mice (E1) were fed during 8 weeks as follows: C1 with normal rodent pellet, O1 with high fat diet, and E1 with high fat diet plus 20 % inulin. C2, O2, and E2 were fed as follows: C2 with normal rodent pellets for 12 weeks; O2 with high fat diet during 8 weeks and switched to normal rodent pellet during next 4 weeks; and E2 with high fat diet over a period of 8 weeks and switched to normal rodent pellet plus 20 % inulin for 4 weeks. Body weight, serum glucose,  triglycerides, total cholesterol, high density lipoprotein (HDL), low density  lipoprotein (LDL), and hepatic α-amylase gene expression were measured.Results: Groups receiving high fat diet showed higher weight (30.71 ± 0.66 g in O2, p &lt; 0.001), nonfasting blood glucose levels (257.69 ± 5.10 mg/dl in O2, p &lt; 0.001), TG (282.15 ± 1.83 mg/dl in O2, (p &lt; 0.001)), and cholesterol levels  (335.72 ± 2.23 mg/dl in O2, (p &lt; 0.001)), compared with control. In C2 group, mean body weight was 25.71 ± 0.54 g, non-fasting blood level 161.54 ± 4.48 mg/dl, TG level 214.29 ± 5.54 mg/dl, and cholesterol level 164.29 ±4.57 mg/dl. Compared to obese group, mice receiving inulin showed lower blood glucose levels (223.10 ± 8.7 mg/dl in E2, p &lt; 0.001), body weight (27.86 ± 0.57 g in E2, p &lt; 0.001), TG (232.14 ± 4.02 mg/dl in E2, p &lt; 0.001) and cholesterol (249.97 ±2.28 in E2, p &lt; 0.001). A slight decrease in hepatic α-amylase gene expression was observed only in E1.Conclusion: Besides its sweetening properties, inulin may also find use as a potential anti-obesity compound.Keywords: High-fat diet, Inulin, Obesity, Blood glucose, Biochemical profil

Comparing the therapeutic effects of 6-gingerol and hydro-alcoholic extract of ginger on polycystic ovary syndrome in Wistar rat

Background and aims: PCOS (polycystic ovary syndrome) is the most common endocrine and metabolic disorder characterized by amenorrhea, hyper androgens, hirsutism, chronic anovulation and infertility. The aim of the present study was determining the effects of ginger extract, and 6-gingerol on hormonal levels and ovarian follicles in induced PCOS rats, and comparing the ameliorating effects of these two substances for treatment of PCOS. Methods: In this experimental research, 42 adult female Wistar rats weighting between 160 g-180 g were divided into six groups of 7 animals. PCOS control that received no injection. PCOS received intraperitoneal injections of 100 mg/kg of ginger extract (for 28 days). Statistical analyses with SPSS, one-way ANOVA, T-test and Duncan test were used to compare groups. Results: In comparison with PCOS control, the treatment of PCOS rats with ginger extract (100 and 200 mg/kg) and 6-gingerol (200 and 400 µg/kg) led to significant decrease in LH levels. There was a decrease in FSH levels, but the significant one was only in the 6-gingerol treated group (400 µg/kg). In PCOS treated groups with ginger extract and 6-gingerol, the serum levels of estradiol decreased significantly compared to control and PCOS control groups (P<0.001). Progesterone levels in PCOS groups injected with ginger extract and 6-gingerol showed a significant increase (P<0.05). In PCOS treated groups with ginger extract and 6-gingerol, testosterone levels decreased significantly (P<0.001, P<0.01, P<0.05). Conclusion: 6-gingerol and ginger extract may be a useful treatment for improving the PCOS through reduction of estrogen, testosterone, LH and FSH, and improvement of ovulation. In fact, because of anti-inflammatory and antioxidant properties of ginger components, especially 6-gingerol, they can cause to improve PCOS

Benzothiazole Thioflavin T improves obesity-related symptoms in mice

Background and Purposes: In order to counteract the obesity epidemics, novel therapeutics are needed. Thioflavin T (ThT) is a benzothiazole used as an amyloid probe and has other properties such as anti-aging and antihyperglycemic effects. The current study aimed at investigating its effect on obesity. Materials and Methods: A mouse model of obesity was generated by feeding male NMRI mice with a high fat diet (HFD) for 8 weeks. After this period, mice diet was switched to normal rodent diet, and ThT was orally administered with a 12 mg/Kg dose. The treatment effect was assessed on biochemical parameters, adipokines (adiponectin and leptin), total antioxidant capacity and TNF-α. Histological investigation was made on samples taken from adipose tissue and liver. Results and Conclusion: After receiving HFD, mice exhibited significantly increased body weight compared with a control group as well as well as abnormality in biochemical parameters. A significantly effective result was obtained on body weight, blood glucose, cholesterol and ALT serum levels which decreased in the treated group. ThT caused also a significant decrease in leptin levels and TNF-α. Furthermore, the compound led to a reduction in the size of adipose tissue cells, as well as the number of lipid droplets in hepatic tissue. In conclusion, it is suggested that ThT possess an interesting potential for being used as an anti-obesity drug, especially when considering its previously reported effects as potential anti-diabetic and anti-ageing compound

The effect of zinc supplemention on glycosylated hemoglobin in type II diabetic patients

زمینه و هدف: دیابت قندی یکی از شایع ترین اختلالات متابولیکی در جهان است که در نتیجه نقص کامل یا نسبی و یا مقاومت به عمل انسولین ایجاد و کنترل نشدن آن موجب بروز عوارض قلبی، عروقی، کلیوی و چشمی می شود. ارتباط روی با سنتز، ترشح وعملکرد انسولین در برخی مطالعات مورد تایید قرار گرفته است. با توجه به اهمیت روی و احتمال کمبود آن در مناطق مختلف ایران، این مطالعه با هدف بررسی تاثیر افزودن روی به رژیم غذایی بیماران دیابتی در میزان کنترل این بیماری انجام شد. روش بررسی: در این مطالعه کارآزمایی بالینی 60 بیمار دیابتی نوع 2 انتخاب و به طور تصادفی به دو گروه 30 نفره تقسیم شدند. به نیمی روزانه 25 میلی گرم و به نیم دیگر روزانه 50 میلی گرم روی به مدت 2 ماه داده شد. قبل و بعد از مداخله در بیماران گلوکز خون ناشتا، گلوکز دو ساعت پس از غذا، هموگلوبین گلیکوزیله و غلظت روی سرم اندازه گیری گردید. اطلاعات جمع آوری شده و نتایج حاصل از آنالیز بیوشیمیایی با استفاده از آزمون های آماری ویلکاکسون و من ویتنی مورد تجزیه و تحلیل قرار گرفت. یافته ها: میانگین غلظت روی سرم و هموگلوبین گلیکوزیله در دوز 25 میلی گرم پس از تجویز میزان روی تغییر معنی داری نشان نداد. ولی در دوز 50 میلی گرم میانگین غلظت روی سرم پس از تجویز روی (ug/dl30±160) نسبت به قبل از تجویز روی (ug/dl30±140) افزایش معنی داری نشان داد (01/0

Citral effect in male NMRI mice nonalcoholic steatosis model: assessing biochemical and histological parameters and PPARα gene expression

Citral is a small molecule present in various citrus species, with reported anti-hyperlipidemic and antiinflammation effects. Here, the effect of intraperitoneal (IP) administration of citral is evaluated in a mouse model of non-alcoholic steatosis. Male NMRI mice were divided into the following groups (n = 12): normal control group (NC) receiving a normal diet; high-fat emulsion group (HF) receiving high fat diet for four weeks; positive control group (C+) receiving HF diet for four weeks and then shifted to normal diet with IP-administered silymarin (80 mg/kg) for four weeks; sham group receiving HF diet for four weeks and then shifted to normal diet for four weeks; and EC1, EC2, and EC3 groups receiving HF diet for four weeks and then shifted to normal diet with IP-administered citral doses of 5, 10, and 20 mg/kg, respectively. HF diet resulted in steatohepatitis with impaired lipid profile, high glucose levels and insulin resistance, impaired liver enzymes, antioxidants, adiponectin and leptin levels, decreased PPARα level, and fibrosis in the liver tissue. Upon treatment with citral, improvement in condition was observed in a dose-dependent manner—both at histological level and in the serum of treated animals. and the PPARα level was also increased