The effect of Fumaria parviflora on the expression of sexual hormones along with their receptors in testicles of adult rats induced by varicocele.

Varicocele (VCL) is a pathological dilation of the venous pampiniform plexus of the spermatic cord and is also classified as male factor infertility. The current experiment aimed to examine the protective effect of Fumaria parviflora (FP), as a powerful antioxidant, against reproductive damage induced by VCL. In this experimental study, 32 male rats were randomly allocated into four groups, namely sham (simple laparotomy without additional intervention), FP (healthy rats administered 250 mg/kg FP), VCL + FP (underwent VCL and received 250 mg/kg FP), VCL (underwent VCL without receiving any treatment). The results showed that the number of Sertoli and germ cells were markedly reduced in the VCL group in comparison to the FP-treated and sham groups. The VCl + FP group had significantly higher serum levels of testosterone (T), FSH, and LH hormones than the VCL group. The quality and motility of spermatozoa were reduced in the VCL group compared with other groups (p ≤ 0.05). Moreover, our findings demonstrated that the administration of FP considerably enhanced the mRNA levels of CatSper-1 and -2, SF-1, 3ß-HSD, 17ß-HSD3, LHCGR, and FSHR (p ≤ 0.05). Based on the obtained results, treatment with FP is capable of preventing testicular dysfunction and elevating the concentration of hormones and some crucial genes, such as CatSper1 and 2, SF-1, 3ß-HSD, 17ß-HSD3, LHCGR, and FSHR that contribute to the spermatogenesis process.

Toxicity effects evaluation of green synthesized silver nanoparticles on intraperitoneally exposed male Wistar rats.

Objective: During the last decades, the widespread use of silver nanoparticles (AgNPs) has been considered because of their small size and antimicrobial effects. The main concern about these particles is that they can induce oxidative stress. In this study, the dose-dependent effects of green synthesized silver nanoparticles (Green-AgNPs) were evaluated on adult male rats.Methods: Animals were injected intraperitoneally (I.P) with the vehicle (deionized water) and different doses of Green-AgNPs (50, 100, 200, and 400 ppm), daily for 21 days. For the safety assessment, body weight and organ coefficient (liver, kidney, spleen, and brain) were measured. The effects of Green-AgNPs administration on working memory, anxiety behavior, novel object recognition, and spatial memory were analyzed. The lipophilic fluorescent products (LFPs), as an indicator of oxidative stress, were also evaluated in the liver, kidney, spleen, and hippocampus.Results: After 21 days of exposure, significant changes were not observed in body weight and organ coefficients. Green-AgNPs at the doses of 100, 200, and 400 ppm caused memory impairment and anxieties as well as altered liver, kidney, spleen, and hippocampus redox status. All tissues of the exposed animals showed an increased LFPs level compared to those of the rats in the vehicle group.Conclusions: This study indicated that the consumption of Green-AgNPs in higher doses (>50 ppm), not only had negative effects on behavioral indices but also caused memory impairment in rats and was toxic. This might be due to the induction of oxidative stress demonstrated by increased LFPs levels in tissues.

Nicotine Augments the Beneficial Effects of Mesenchymal Stem Cell-based Therapy in Rat Model of Multiple Sclerosis.

Experimental autoimmune encephalomyelitis (EAE) in rats through immunization with guinea pig spinal cord homogenate (GPSCH) produces a chronic disease with a relapsing pattern such as multiple sclerosis (MS) in humans. In previous studies, the immunomodulatory benefits of mesenchymal stem cells (MSCs) and nicotine have already been determined. Thus, this research was conducted to assess the additional benefits of the combination therapy of MSCs and nicotine in a rat model of MS. EAE was induced by GPSCH and complete Freund's adjuvant (CFA) in female Wistar rats. The therapies were initiated at day 12 post-immunization (p.i.), when the rats developed a neurological disability score. The symptoms were recorded daily until day 33, when the rats were sacrificed. Finally, the splenocytes were evaluated by Enzyme-linked immunosorbent assay (ELISA) for cytokine production. The therapeutic treatment in the EAE rats with a combination of MSCs and nicotine exhibited a more desirable outcome, causing the regression of the average mean clinical score and neuropathological features to be more favorable than the treatment with either therapy alone. The combination therapy led to a significant reduction in the cumulative disease disability from day 21. For the EAE rats treated with nicotine and MSCs, this period was started from day 22 and 28 p.i., respectively. Besides the increase in the levels of IL-10, the combined therapy significantly reduced the splenocytes production of pro-inflammatory IL-17 as well as TNF-α more profoundly than either of the medications alone. In conclusion, the combination of MSCs and nicotine can be suggested as a promising strategy for further MS therapeutics improvement.

Molecular effects of curcumin on the experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). Previous studies have shown that myelin degradation during MS and EAE resulted in reduced expression of some of the proteins, e.g., the MBP (myelin basic protein), and increased expression of genes such as iNOS (Inducible nitric oxide synthase) and NOGO-A in the affected patients. In the present study, EAE was induced by immunizing Wistar rats (n=12) with homogenized spinal cord of guinea pig and Freund's complete adjuvant. Curcumin is an active ingredient in turmeric with anti-inflammatory properties, which has been studied in this article. In this study, the effect of curcumin administration on the change of the expression of MBP, NOGO-A, and iNOS genes was evaluated using the RT-PCR (Reverse transcription-polymerase chain reaction) technique. The obtained results indicated it could be concluded that curcumin was able to improve EAE by increasing the amount of MBP gene expression and reducing the intensity of NOGO-A expression.

Vitamin D3 attenuates oxidative stress and cognitive deficits in a model of toxic demyelination.

OBJECTIVES: Multiple sclerosis (MS) is a demyelinating disease. The prevalence of MS is highest where environmental supplies of vitamin D are low. Cognitive deficits have been observed in patients with MS. Oxidative damage may contribute to the formation of MS lesions. Considering the involvement of hippocampus in MS, an attempt is made in this study to investigate the effects of vitamin D3 on behavioral process and the oxidative status in the dorsal hippocampus (CA1 area) following the induction of experimental demyelination in rats. MATERIALS AND METHODS: Animals were divided into six groups. CONTROL GROUP: animals received no surgery and treatment; saline group: animals received normal saline; sham group: animals received 150 µl sesame oil IP; vitamin D3 group: animals received 5 µg/kg vitamin D3 IP; lysophosphatidyl choline (LPC) group (toxic demyelination's model): animals received LPC by stereotaxic intra-hippocampal injection of 2 µl LPC in CA1 area; Vitamin D3- treated group: animals were treated with vitamin D3 at doses of 5 µg/kg IP for 7 and 21 days post lesion. The spatial memory, biochemical parameters including catalase (CAT) activities and lipid peroxidation levels were investigated. RESULTS: Animals in LPC group had more deficits in spatial memory than the control group in radial arm maze. Vitamin D3 significantly improved spatial memory compared to LPC group. Also, results indicated that vitamin D3 caused a decrease in lipid peroxidation levels and an increase in CAT activities. CONCLUSION: Current findings suggest that vitamin D3 may have a protective effect on cognitive deficits and oxidative stress in toxic demyelination's model.

Dibutyryl cyclic AMP inhibits the progression of experimental autoimmune encephalomyelitis and potentiates recruitment of endogenous neural stem cells.

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Cyclic AMP and its analogs enhance regeneration of adult mammalian central nervous system (CNS). Endogenous neural stem cells (NSCs) play a pivotal role in CNS regeneration, producing new neuron and glial cells. Here, we examined the effect of dibutyryl cyclic AMP (dbcAMP) on experimental autoimmune encephalomyelitis (EAE) symptoms, endogenous remyelination, and recruitment of NSCs. EAE was induced by immunizing mice using myelin oligodendrocyte glycoprotein peptide and pertussis toxin. Proliferative cells within CNS were labeled using repetitive systemic injections of 5-bromo-2-deoxyuridine (BrdU) before EAE induction. Myelin staining was performed using Luxol fast blue. The number of nestin(+) and BrdU(+) cells in subventricular zone (SVZ) and olfactory bulb (OB) was evaluated using immunohistochemistry. dbcAMP suppressed EAE progression and decreased the extent of demyelinated plaques in the lumbar spinal cord. EAE induction reduced the number of proliferative cells in SVZ and increased their population in OB. EAE also increased the number of nestin(+) cells in OB. We also found that dbcAMP increased the recruitment of NSCs into the OB and brain parenchyma of EAE mice. Our results suggest dbcAMP as a potential therapy for inducing myelin repair in the context of demyelinating diseases like multiple sclerosis. Its positive effect seems to be mediated, at least partially, by endogenous neural stem cells and their increased recruitment.

Effect of basic fibroblast growth factor on cardiomyocyte differentiation from mouse embryonic stem cells.

OBJECTIVE: To investigate the effect of basic fibroblast growth factor (bFGF) on the differentiation of embryonic stem cells (ESCs) into early cardiomyocytes. METHODS: Embryoid bodies (EBs) were produced from mouse ESC line (Royan B1) in hanging drops and cultured for 5 days as suspension. During the first 2 days of suspension, the EBs of the experimental group were treated with 10 ng/ml of bFGF and subsequently plated onto gelatin-coated tissue culture dishes (day 7). The differentiated cells were evaluated pharmacologically, by immunocytochemistry, and so forth. The study was carried out in the Department of Stem Cells, Royan Institute, Tehran, Iran in 2005. RESULTS: The beating frequency in the bFGF treated EBs was less than that in the control group. In addition, the beating in the EBs of the experimental group, treated with isoprenaline and phenylephrine, was only more than 7+3 days in comparison to the control group. The response of the EBs to carbachol was more in the bFGF group than 7+14 days. In all the stages of development, the beating cells in the EBs of both groups expressed beta-actinin, myosin light chain isoform 2V, cardiac alpha-myosin heavy chain (alpha-MHC), and cardiac beta-myosin heavy chain (beta-MHC). Nonetheless, during 7+3 days, the last 2 genes were more advanced in the bFGF group. The atrial natriuretic factor was also expressed at a late stage in both groups. CONCLUSION: Basic fibroblast growth factor can only promote the early maturation of ESC-derived cardiomyocytes in terms of chronotropic characteristics and expression of cardiac alpha-MHC and beta-MHC.