The effect of sulfoxo-bilactam-21-crown -7 on spermatogenesis in immature Balb/c mice

زمینه و هدف: کراون اترها ملکول های میزبان برای یون های فلزی و غیر فلزی هستند. توانایی کراون اترها در کنترل سیکل و تغییر فعالیت برخی از آنزیم ها گزارش شده است. در این مطالعه اثر یک کراون اتر جدید (سولفوکسو- بی لاکتام- 21- کراون-7) بر روی بافت بیضه و اسپرماتوژنز مورد بررسی قرار گرفته است. روش بررسی: در این مطالعه 24 سر موش نابالغ کوچک آزمایشگاهی (Balb/C) به سه گروه گروه کنترل (هیچ ماده ای دریافت نکردند)، شم )فقط توئین 80 دریافت کردند) و تجربی )سولفوکسو- بی لاکتام- 21- کراون-7 دریافت کردند) تقسیم شدند. Lethal dose 50 (LD50) دارو، به میزان 40 میلی گرم بر کیلوگرم تعیین شد. بر این اساس، دوز 20 میلی گرم بر کیلوگرم از این کراون اتر به روش درون صفاقی هر روز به مدت یک هفته به گروه تجربی تزریق شد. دو هفته پس از آخرین تزریق، حیوانات بیهوش شده و کشته شدند. خون جهت اندازه گیری هورمون از قلب گرفته شد. بافت بیضه، استخراج شد و جهت مطالعات بافت شناسی فیکس گردید. داده ها توسط آنالیز واریانس یکطرفه (ANOVA) و به دنبال آن تست توکی آنالیز شدند. یافته ها: تزریق درون صفاقی سولفوکسو- بی لاکتام- 21- کراون-7 (20 میلی گرم بر کیلوگرم) تغییر معنی داری در تعداد اسپرماتوگنی نوع A و B، اسپرماتوسیت اولیه و سلول های لیدیک در گروه تجربی در مقایسه با گروه کنترل و شم نشان نداد. افزایش هورمون جنسی مردانه، تستوسترون (001/0

Effect of Vitex agnus-castus ethanolic extract on hypothalamic KISS-1 gene expression in a rat model of polycystic ovary syndrome

Objective: Polycystic ovary syndrome (PCOS) is an endocrine system disruption that affects 6-10% of women. Some studies have reported the effect of Vitex agnus-castus (Vitagnus) on the hypothalamic-pituitary-gonad axis (HPG). This study was conducted to investigate Vitagnus effect on the expression of kisspeptin gene in a rat model of PCOS. Materials and Methods: Thirty-two female rats were distributed into: control, Vitagnus-treatment (365 mg/kg for 30 days), PCOS (Letrozole for 28 days) and PCOS animals treated with Vitagnus (30 days of Vitagnus after PCOS induction). At the end of the treatments, serum and ovaries were collected for analysis. Expression level of KISS-1 gene in the hypothalamus was investigated, using Real-Time-PCR. Results: In the PCOS group compared to control, FSH, progesterone and estradiol levels were decreased, whereas testosterone and LH levels were significantly increased. No significant changes were observed in the Vitagnus-treated animals in compare to control.  However, Vitagnus treatment in the PCOS group, resulted in a raise in progesterone, estrogen and FSH levels and a reduction in the levels of testosterone and LH. Quantitative gene expression analysis showed that PCOS induction resulted in over-expression of KISS-1 gene, however, Vitagnus treatment reduced this up-regulated expression to normal level. Conclusion: In conclusion, our results indicated that Vitagnus extract inhibited downregulation of KISS-1 gene in the hypothalamus of PCOS rats. Because of the master role of kisspeptin in adjusting the HPG axis, Vitagnus is likely to show beneficial effects in the treatment of PCOS via regulation of kisspeptin expression. This finding indicates a new aspect of Vitagnus effect and may be considered in its clinical applications

The protective effect of ZnO nanoparticles on liver and impairments induced by Paclitaxel treatment in female Wista rat

Paclitaxel is a chemotherapy drug inhibiting cell growth. In some studies, patients with normal liver function have experienced increase in bilirubin, ALT and AST by using paclitaxel. The aim of this study was to evaluate the ef-fect of intra-peritoneal injection of doses 5 and 10 mg/kg nZnO on the liver of rats treated with paclitaxel. 35 adult fe-male Wistar rats were divided into 7 groups including control, sham (saline injection), experimental groups1 and 2 (nZnO injection), experimental group 3 (paclitaxel injection), experimental groups 4 and 5 (nZnO and paclitaxel inje-ction). Liver function was examined 28 days after the end of injection. Experimental group3 had large and swollen liver morphology. Most hepatocytes had dense nuclei and changed cell shape indicating of cell death. Blood test showed si-gnificant increase in the levels of ALT, AST and bilirubin and decrease in the level of ALP in comparison with the co-ntrol group. In experimental groups 4 and 5, cell shape alterations, increase in cell death and increase in liver markers were remarkably reduced in comparison with the experimental group 3, in a way that there were no significant differ-ences with the control group. No significant differences were observed between the control group and experimental gr-oups 1 and 2. According to the findings, nZnO can reduce the side effects of paclitaxel on liver tissue

Evaluation of The Protective Effect of Hydro-Alcoholic Extract of Raspberry Fruit on Aquaporin1 Expression in Rats Kidney Treated by Methotrexate

Objective Methotrexate (MTX) is an antimetabolite drug commonly prescribed for the various cancers and autoimmune diseases. Despite its considerable therapeutic effects, nephrotoxicity is the most important side-effect of treatment with MTX. Aquaporin1 (AQP1) is a water channel proteins which is present in mammalian kidney. Raspberry fruit with antioxidant properties is able to protect biological systems from the harmful effects of free radicals. The purpose of this study was to investigate the effect of raspberry extract on expression of AQP1 and the MTX-induced nephrotoxicity in rats. Materials and Methods In this experimental study, 60 adult male Wistar rats were divided into nine groups including control, sham, MTX treated group [single dose of 20 mg/kg of body weight (BW) MTX at the third day], raspberry treated groups [intraperitoneal (I.P) injection of 100, 200, 400 mg/kg of BW raspberry extract for ten consecutive days], MTX and raspberry treated groups. At day 11, rats were sacrificed via chloroform inhalation and kidney tissues were fixed in formalin solution for histological and immunohistochemistry analysis. The serological assays for urea, creatinine, uric acid and interleukin-6 (IL-6) levels were also performed. Results MTX elevated serum level of the urea, creatinine, uric acid, IL-6, renal tissue damage and decreased the AQP1 expression level. Raspberry fruit extract improved the kidney function and reduced side effects of MTX in treated rats. Expression of AQP1, in a dose dependent manner was also ameliorated, as compared to control group. Conclusion According to the findings of this study, it can be concluded that biological activity of compounds presented in raspberry fruit extract especially anthocyanins may have chemo-protective effect on kidney function and AQP1 expression in rats treated by MTX

The adverse effects of the methoxsalen and ultraviolent A radiation on spermatogenesis in mice

Background: Different investigation showed that 5-methoxypsoralen and 8- methoxypsoralen reduce birth rates in the rats. Objective: In this study we worked out the effect of methoxsalen together with ultraviolent A (UVA) radiation on mature Balb/C mice spermatogenesis. Materials and Methods: The LD50 standard was determined 160 mg/kg and the UVA dose which causes erythema was calculated 0.046 J/cm2. A sub-lethal dose of 80 mg/kg of methoxsalen solution was injected intrapritoneally to mature mice and after one hour they were exposed to UVA radiation for 20 minutes. Experiments applied included methoxsalen alone, methoxsalen with UVA, UVA alone, sham group (a group received Tween 80), and control group (N=6). In all experimental groups except UVA alone group, injections were carried out, during two consecutive weeks. Serial cross sections (5 µm thickness) were prepared for morphological and histological studies. Tunica albuginea diameter, and number of type A and type B spermatogonia and histological investigation of the testes were measured. Results: Microscopical and statistical analyses showed significant anomalies among the experimental groups compared to control and sham group. These anomalies included decrease the body weight; increase the relative testis weight; and decrease the number of spermapogonia (type A and B), primary spermatocytes, spermatids and sperms in experimental groups I and II compared to control group. Our results showed the number of spermatozoa in experimental group I was 22.6±2.12, in experimental group II was 33.6±2.05 and in control group was 44.3±2.77 (p<0.05). Moreover in some experimental groups (I and II) shrinkage of seminiferous tubules and release of primary spermatocyte and spermatids were observed to the lumen of them. Conclusion: It is concluded from the results of this work that treatment with methoxsalen with UVA can damage and disorganize seminiferous tubules and decrease spermatogenic cells

Differentiation of endometrial stem cells into motor neurons by the use of purmorphamin small molecule

Background: Small molecule Purmorphamin (PMA) is the agonist of smoothened protein in Sonic hedgehog (Shh) signaling pathway. Effect of purmorphamin small molecule on differentiation of mesenchymal cells into bone tissue has been studied previously. Use of Shh causes progression of neural differentiation, and the differentiated cells express specific neural markers. Neurofilament (NF) and acetylcholine esterase (Chat) are specific markers of motor neurons and their expression in differentiated cells indicates their conversion into motor neurons. The aim of this study was to evaluate the ability of PMA to differentiate the human endometrial stem cells (hEnSCs) into motor neurons. Methods: This analytical study was done in Tehran University of Medical Sciences laboratory on September of 2015. In this study hEnSCs were enzymatically extracted from endometrial tissue. After third passages, the flow cytometry was done for mesenchymal stem cells markers. The mesenchymal stem cells were divided into control and differentiated groups. FBS 10%+DMEM/F12 was added to the culture medium of control group and the differentiating group was treated with differentiating medium containing N2, PMA, DMEM/F12, FBS, B27, IBMX, 2ME, FGF2, RA, BDNF. After 21 days immunocytochemistry (ICC) test was done for the expression of NF and Chat proteins and Real-time PCR analysis for expression of neural markers such as NF, Chat, Nestin and GFAP (as glial marker) at mRNA level. Results: The flow cytometry analysis showed that hEnSCs were positive for mesenchymal markers CD90, CD105 and CD146 and negative for endothelial marker CD31, and hematopoietic marker CD34. The immunocytochemistry and Real time-PCR results showed that the cells treated with PMA expressed motor neuron markers of NF and Chat. Conclusion: According to the results of this study, it can be concluded that small molecule PMA has the potency to induce the differentiation of hEnSCs into neural cells, specifically motor neurons by activating Shh signaling pathway

The Adverse Effects of Methoxsalen on The Oogenesis of Balb/C Mice

Objective: Methoxsalen is a natural photoactive compound which is found in many seed plants. A number of epidermal proliferative disorders can be treated by methoxsalen along with long wave ultraviolet A (UVA).Materials and Methods: In an experimental study, we aimed to demonstrate the effect of methoxsalen, UVA and their combination on oogenesis Balb/C mice. There were two experimental groups and a control group. The experimental groups were composed of i. a short term group with treatment duration of 15 days and ii. a long term group with treatment duration of 5 weeks. Both the long term and short term experimental groups were further subdivided into a UVA group, a methoxsalen group and a methoxsalen plus UVA group. After treatment, mature females in prosterus phase of ovarian cycle were scarified with ether, while their ovaries were removed and prepared for histological studies.Results: Both macro and microscopic studies showed significant anomalies (p<0.05) among experimental group ovaries as compared to control group. The obtained results showed a significant decrease in the following factors: number and diameter of corpus lutei, Graafian follicles, diameter of granulosa cell layer and oocytes, number of primordial،and primary and growing follicles, while we observed an increase in number of atretic follicle. Furthermore, our findings confirmed an increase in theca diameter only through UVA treatment. Methoxsalen also reduced circulating estrogen levels in blood serum, significantly. Other cases of teratogenecity, such as follicles with three oocytes and disorganization in corpus luteum cells were observed.Conclusion: The result suggests that UVA, methoxsalen and their combination cause health problems and cell injuries

In vitro transfection of anti-tumor miR-101 induces BIM, a pro-apoptotic protein, expression in acute myeloid leukemia (AML)

Acute myeloid leukemia (AML) frequently relapses after initial treatment, though it is possible that drug resistance occurs. Hence, it seems necessary to develop novel therapies such as gene therapy specifically via miRNA trans- fection. MicroRNA-101 has been considered as a tumor suppressor in different types of cancer. It is demonstrated that exogenous miR-101 transfection is associated with decreased viability in AML in this paper. Besides, the increase of pro-apoptotic protein BIM expression in both mRNA and protein level has been illustrated. The recent findings provide an insight into the novel function of miR-101 in AML by activating BIM as an important mediator in intrinsic apoptosis pathways. Generally, miR-101 has been considered as a therapeutic target in our data and might have a valuable role in AML

Evaluation of Oogenesis Aspects in Neonatal and Adult Mice after Toloaldoxime Treatment

Objective: Oximes are important materials in organic chemistry. Synparamethyl benzaldehyde oxime (toloaldoxime) is structurally similar to other oximes, hence we have studied its effects on the neonatal and adult female Balb/c mice reproductive systems in order to provide a platform for future studies on the production of female contraceptive drugs. Materials and Methods: In experimental study, we studied the effects of toloaldoxime on ovary growth and gonadal hormones of neonatal and adult Balb/c mice. A regression model for prediction was presented. Results: The effects of toloaldoxime on neonatal mice were more than adult mice. The greatest effect was on the number of Graafian follicles (59.6% in adult mice and 31.83% in neonatal mice). The least effect was on ovary weight, and blood serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). Conclusion: According to the data obtained, toloaldoxime can be considered an antipregnancy substance