ABSTRACT
Background: Cutaneous leishmaniasis is one of the most important parasitic diseases in humans. In this disease, one of the responsible organisms is Leishmania major, which is transmitted by sandfly vector. There are specific differences in biochemical profiles and metabolite pathways in logarithmic and stationary phases of Leishmania parasites. In the present study, [1]H NMR spectroscopy was used to examine the metabolites outliers in the logarithmic and stationary phases of promastigotes in L. major to enlighten more about the transmission mechanism in metacyclogenesis of L. major
Methods: Promastigote was cultured, logarithmic and stationary phases were separated by the peanut agglutinin, and cell metabolites were extracted. [1]H NMR spectroscopy was applied, and outliers were analyzed using principal component analysis
Results: The most altered metabolites in stationary and logarithmic phases were limited to citraconic acid, isopropylmalic acid, L-leucine, ornithine, caprylic acid, capric acid, and acetic acid
Conclusion: [1]H NMR spectroscopy could play an important role in the characterization of metabolites in biochemical pathways during a metacyclogenesis process. These metabolites and their pathways can help in exploiting a transmission mechanism in metacyclogenesis, and outcoming data might be used in the metabolic network reconstruction of L. major modeling
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Background: So far, non-invasive diagnostic approaches such as ultrasound, magnetic resonance imaging, or blood tests do not have sufficient diagnostic power for endometriosis disease. Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis
Objective:The present study focuses on the identification of predictive biomarkers in serum by pattern recognition techniques and uses partial least square discriminant analysis, multi-layer feed forward artificial neural networks [ANNs] and quadratic discriminant analysis [QDA] modeling tools for the early diagnosis of endometriosis in a minimally invasive manner by [1]H- NMR based metabolomics
Materials and Methods:This prospective cohort study was done in Pasteur Institute, Iran in June 2013. Serum samples of 31 infertile women with endometriosis [stage II and III] who confirmed by diagnostic laparoscopy and 15 normal women were collected and analyzed by nuclear magnetic resonance spectroscopy. The model was built by using partial least square discriminant analysis, QDA, and ANNs to determine classifier metabolites for early prediction risk of disease
Results:The levels of 2- methoxyestron, 2-methoxy estradiol, dehydroepiandrostion androstendione, aldosterone, and deoxy corticosterone were enhanced significantly in infertile group. While cholesterol and primary bile acids levels were decreased. QDA model showed significant difference between two study groups. Positive and negative predict value levels obtained about 71% and 78%, respectively. ANNs provided also criteria for detection of endometriosis
Conclusion:The QDA and ANNs modeling can be used as computational tools in noninvasive diagnose of endometriosis. However, the model designed by QDA methods is more efficient compared to ANNs in diagnosis of endometriosis patients
ABSTRACT
Chlorpromazine [CPZ], an antipsychotic drug, is associated with increased risk of sexual dysfunction through increasing prolactin levels. The current study evaluates the effect of CPZ-induced hyperprolactinemia on ovarian follicular growth, gonado-tropins, and alteration of ovarian source hormones. In this experimental study, animals were divided into four groups, control and CPZ [n=8 per group]. In the treated groups, CPZ was administered by gavage at doses of 3, 10 and 30 mg/kg per day for 28 days. On day 29 the animals were killed after which histopathological and histomorphometric analyses of the ovaries were performed. We evaluated the levels of prolactin serum, luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E[2] and progesterone. The ovaries of the test groups showed numerous atretic follicles of various sizes. CPZ caused a significant difference between the test groups and the control group [P<0.05] on the amount of atresia and the size of the normal corpora lutea [CL]. The increased dysfunction of the ovaries from the different groups depended on the amount of CPZ administered. The serum concentrations of prolactin and progesterone significantly increased [P=0.05], while the serum concentrations of estradiol, LH and FSH notably decreased [P=0.05], depending on the CPZ dose. CPZ-induced animals had unsuccessful mating and decreased pregnancy rate. The present findings suggest that CPZ-induced disturbances not only depend on prolactin level but the increased prolactin level is largely dose-dependent
ABSTRACT
Hyperprolactinemia is a common side effect of antipsychotic drugs that requires further investigation. The current study was designed to evaluate dose-dependent effect of chlorpromazine [CPZ] on hormonal changes and uterine horn histological structure in rats. Moreover, the mammary glands were analyzed to show hyperprolactinemia-induced histological changes. Albino Wistar rats [n = 32] were divided into four groups. The first group was set as a control. In the three drug-treated groups [eight rats in each group], CPZ was administered by a gavage at doses of 3, 10, and 30 mg/kg/day for 28 days. One day after the last administration of the drug, the animals were sacrificed. Histopathological and histomorphometrical analyses of the uterine horns and mammary glands were carried out to evaluate dose-dependent effect of CPZ on histological structure. Serum levels of prolactin [PRL], estradiol, progesterone, follicle-stimulating hormone [FSH], and luteinizing hormone [LH] were also evaluated. Remarkable [P < 0.05] elevation was observed in CPZ-administrated animals' uterine horn endometrium, myometrium, and perimetrium thicknesses, and the mammary glands were observed with galactorrhea features. The serum level of progesterone and PRL significantly [P < 0.05] increased, while the serum concentration of LH, FSH, and estradiol was notably [P < 0.05] decreased depending on administrated CPZ dose. No histological and biological changes were occurred in the control animals. The present findings suggest that CPZ-induced disturbances not only depend on PRL level and increased PRL level largely depends on administrated doses of the CPZ
Subject(s)
Animals, Laboratory , Chlorpromazine , Uterus , Rats, WistarABSTRACT
The aim of this study was the effect of Myrtus communis extract on liver enzymes and blood biochemical factors in diabetic adult male rats. This study has been carried out experimentally and completely random. Seventy adult male Wistar rats were divided in 7 groups including: control which received no treatment, sham who received 2 mL of distilled water, the 1st, 2nd and 3rd experimental groups which received 0.75, 1.5 and 3 mg/kg Myrtus communis leaf extract respectively, the 4th experimental group as the diabetic control group who received streptozotocin [60 mg/kg] and the 5th experimental group as the diabetic treatment group who received 3 mg/kg of extract. This experiment lasted 14 days with prescript orally. After this period, all the rats, were weighted, anesthetized and blood samples were taken from the heart centrifuged and sera were evaluated for the concentration of various factors. In addition liver were removed and sliced. According to the obtained results, the plasma concentration of liver enzyme [alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase], cholesterol and glucose presented a significant decrease at [p
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Background: elevated level of plasma homocysteine has been related to various diseases. Patients with hyperhomocysteinemia can develop hepatic steatosis and fibrosis. We hypothesized that oxidative stress induced by homocysteine might play an important role in pathogenesis of liver injury. Also, the cellular response designed to combat oxidative stress is primarily controlled by the transcription factor Nrf2, a principal inducer of anti-oxidant and phase II-related genes
Methods: hepG2 cells were treated with homocysteine in different time periods. Glutathione content was measured by flowcytometry. Using electrophoretic mobility shift assay [EMSA] and Western-blotting, anti-oxidant response element [ARE]-binding activity of Nrf2 for heme ocygenase-1 [HO-1] was demonstrated. Real time RT-PCR and Western-blotting were performed to evaluate whether homocysteine was able to induce mRNA and protein expression of HO-1
Results: the role of Nrf2 in cellular response to homocysteine is substantiated by the following observations in HepG2 cells exposed to homocysteine [i] Western-blotting revealed that Nrf2 is strongly stabilized and became detectable in nuclear extracts. [ii] EMSA demonstrated increased binding of Nrf2 to oligomers containing HO-1 promoter-specific ARE-binding site. [iii] Real time RT-PCR and Western-blotting revealed increased mRNA and protein expression of inducible gene HO-1 after treatment with Homocysteine
Conclusion: data presented in the current study provide direct evidence that the immediate cellular response to oxidative stress provoked by homocysteine is orchestrated mainly by the Nrf2-ARE pathway. Therefore, induction of Nrf2-ARE-dependent expression of HO-1 could be a therapeutic option for hepatic cells damage induced by homocysteine. Iran. Biomed. J. 17 [2]: 93-100, 2013
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Acyclovir [ACV], a synthetic purine nucleoside analogue derived from guanosine, is known to be toxic to gonads and the aim of this study was to evaluate the effect of ACV on the sperm parameters and testosterone production in rat. In this experimental study, forty adult male Wistar rats [220 +/- 20 g] were randomly divided into five groups [n=8 for each group]. One group served as control and one group served as sham control [distilled water was intraperitoneally [i.p.] injected]. ACV was administered intraperitoneally in the drug treatment groups [4, 16 and 48 mg/kg/day] for 15 days. Eighteen days after the last injection, rats were sacrificed by CO2 inhalation. After that, cauda epididymides were removed surgically. At the end, sperm concentrations in the cauda epididymis, sperm motility, morphology, viability, chromatin quality and DNA integrity were analyzed. Serum testosterone concentrations were determined. The results showed that ACV did not affect sperm count, but decreased sperm motility and sperm viability at 16 and 48 mg/kg dose-levels. Sperm abnormalities increased at 48 mg/kg dose-level of ACV. Further, ACV significantly increases DNA damage at 16 and 48 mg/kg dose-levels and chromatin abnormality at all doses. Besides, a significant decrease in serum testosterone concentrations was observed at 16 and 48 mg/ kg doses. The present results highly support the idea that ACV induces testicular toxicity by adverse effects on the sperm parameters and serum level of testosterone in male rats
Subject(s)
Male , Animals, Laboratory , Testicular Diseases/chemically induced , Spermatozoa/drug effects , Acyclovir/analogs & derivatives , Testosterone/blood , Rats, WistarABSTRACT
This study investigated whether trinitroglycerine (TNG) as nitric oxide (NO) releasing agent had anti-leishmanial effects and mediated pathology in BALB/c mice infected with Leishmania major. Cutaneous leishmaniasis (CL), a zoonotic infection caused by leishmania protozoa is still one of the health problems in the world and in Iran. NO is involved in host immune responses against intracellular L. major, and leishmania killing by macrophages is mediated by this substance. Moreover, application of CL treatment with NO-donors has been recently indicated. In our study, TNG was used for its ability to increase NO and to modify CL infection in mice, in order to evaluate NO effects on lesion size and formation, parasite proliferation inside macrophages, amastigote visceralization in target organs, and NO induction in plasma and organ suspensions. Data obtained in this study indicated that TNG increased plasma and liver-NO, reduced lesion sizes, removed amastigotes from lesions, livers, spleens, and lymph nodes, declined proliferation of amastigotes, hepatomegaly, and increased survival rate. However, TNG reduced spleen-NO and had no significant effects on spelenomegaly. The results show that TNG therapy reduced leishmaniasis and pathology in association with raised NO levels. TNG had some antiparasitic activity by reduction of positive smears from lesions, livers, spleens, and lymph nodes, which could emphasize the role of TNG to inhibit visceralization of L. major in target organs.