Effects of co-administration of rapamycin and evening primrose/hemp seed oil supplement on immunologic factors and cell membrane fatty acids in experimental autoimmune encephalomyelitis.

BACKGROUND: The immune response is influenced by the administration of omega-3 polyunsaturated fatty acids (PUFA). Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE) are affected by PUFA. The combination of evening primrose/hemp seed oil (EPO/HSO) has essential fatty acids (EFAs) for human optimal health due to the favorable ratio of omega-6/omega-3 and antioxidantal properties. The study was conducted to evaluate the effects of EPO/HSO on improving the membrane fatty acids composition of spleen and blood cells and immunologic factors in compared to rapamycin (RAPA) in the EAE model. METHODS AND MATERIALS: Chronic-EAE was induced by induction of MOG in C57BL/6J mice (female, age: 6-8 weeks, weight 18-21). Mice were assigned to 5 groups (6/group) to evaluate the therapeutic effects of EPO/HSO supplement in comparison with rapamycin: A group; EPO/HSO + RAPA, B group; RAPA, C group; EPO/HSO. Results were compared to two control groups (EAE and naive). The fatty acid profile of the spleen and blood cell membrane was evaluated. Real-time-polymerase chain reaction was used for the evaluate the genes expression levels of interleukin (IL) -4, IL-5, and IL-13 in lymphocytes. Also, IL-4 of serum was evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our findings indicated that EPO/HSO therapy significantly increased the percentage of essential fatty acids in cell membrane of the spleen and blood. The relative expression of IL-4, IL-5, and IL-13 genes in lymphocytes and serum level of IL-4 was significantly increased in the HSO/EPO treated group versus other groups. CONCLUSION: These results point to potential therapeutic effects on the repair of the structure of cell membranes and suppression of inflammation by EPO/HSO in EAE.

The Effects of Evening Primrose/Hemp Seed Oil Compared to Rapamycin on the Gene Expression of Immunological Parameters in Experimental Autoimmune Encephalomyelitis Splenocytes.

Mouse model of multiple sclerosis (MS) is used for the inflammatory demyelinating disease. Rapamycin (RAPA) may contribute to the reduction of inflammatory responses to experimental autoimmune encephalomyelitis (EAE). Due to its adverse side effects, identifying new therapeutic agents is important. We investigated the transcriptional effects of evening primrose/hemp seed oil (EP/HS oil) compared to RAPA on the expression of immunological factors genes in spleen cells of EAE mouse models. We firstly induced EAE mice by injection of myelin oligodendrocyte glycoprotein (MOG). Then, the EAE mice treated and untreated with EP/HS oil were evaluated and compared with naïve mice. The spinal cords were examined histologically. The immunological factors including genes expression of the regulatory-associated protein of mammalian target of rapamycin (RAPTOR), regulatory-associated companion of mammalian target of rapamycin (RICTOR), interferon (IFN)-γ, interleukin (IL)-10, signal transducer and activator of transcription factors (STAT3), forkhead box P3 (FOXP3), and IL-17 of splenocytes were evaluated by real time-polymerase chain reaction (RT-PCR). The data showed that EP/HS oil was able to reduce the severity of EAE and inhibited the development of the disease. EP/HS oil treatment significantly inhibited the expression of RAPTOR, IFN-γ, IL-17, and STAT3 genes and promoted the expression of RICTOR, IL-10, and FOXP3 genes. In conclusion, the EP/HS oil is likely to be involved in transcription of factors in favor of EAE improvement as well as participating in remyelination in the EAE spinal cord and that it suggests to be effective in therapeutic approaches for MS.

Long-term ethanol consumption promotes changes in ß-defensin isoform gene expression and induces structural changes and oxidative DNA damage to the epididymis of rats.

Chronic alcohol ingestion causes sexual dysfunction, impairs sperm motility and fertility, and changes semen quality. Considering the key role of epididymis in sperm development, the aim of the present study was to evaluate the effects of long-term ethanol consumption on epididymis changes, including alterations in ß-defensin isoform gene expression, oxidative stress, and pathological changes, such as cell proliferation and fibrosis in the epididymis of rats. In this study, male Wistar rats were equally divided into control and ethanol (4.5 g/kg BW) groups. After six weeks of treatment, the results revealed the proliferation of epididymis cells, fibrosis in the epididymis tissue, and a significant rise in the level of 8-OHdG and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the ethanol group, compared with the control group. Moreover, the ethanol group showed an increase in the gene expression of epididymal ß-defensin isoforms 15 and 21 and a reduction in the gene expression of ß-defensin isoforms 27 and 30, compared with the controls. These findings indicate that ethanol-induced epididymal damage and sperm abnormalities might be partly associated with changes in ß-defensin isoforms and epididymal structure, mediated by the increased activities of 8-OHdG and NADPH oxidase.

The Effect of Chronic Ethanol Consumption on Sexual Motivation and Behavior of Adult Male Wistar Rats in the Copulatory Phase.

BACKGROUND: The interaction of ethanol consumption and sexual behavior has been evaluated over the past three decades; however, some studies have assessed how ethanol consumption affects the general behavioral aspects of the copulatory cycle patterns in male rats. The aim of this study was to investigate the effect of chronic ethanol consumption on adult male Wistar rats' sexual motivation and behavior alteration in pre-copulatory, copulatory, and executive phases of the copulatory cycle. METHODS: Male Wistar rats were randomly allocated to two groups (control and ethanol treated groups). After 42 days of treatment, male rats were given access to adult female rats for 2 hours and their sexual behavior were recorded in a fully dark room using an infrared camera. FINDINGS: Chronic ethanol consumption caused a significant increase in anogenital sniffing and mounting, intermission, and ejaculation latencies periods, as well as a significant decrease in the sexual activity index (SAI) and copulatory efficiency (CE) compared to the control group. CONCLUSION: It is suggested that chronic ethanol consumption suppresses sexual behavior and reduces male rats' tendency toward sexual interaction with female rats as manifested by the enhanced latency periods in the copulatory phases and reduced SAI of ethanol treated animals.

Chronic ethanol ingestion induces glomerular filtration barrier proteins genes expression alteration and increases matrix metalloproteinases activity in the kidney of rats.

BACKGROUND: Chronic alcohol ingestion-induced kidney structure and function alterations are very well known, but the precise underlying molecular mediators involved in ethanol-induced kidney abnormalities remain elusive. The aim of this study was to investigate the effect of chronic ethanol exposure on matrix metalloproteinase 2, 9 (MMP), glomerular filtration barrier proteins (nephrin and podocin), as well as vascular endothelial growth factor receptor 1, 2 (VEGFRs) isoforms gene expression in the kidney of rats. METHODS: Sixteen male Wistar rats with an initial body weight of 220 ± 10 g were divided into the following two groups: (1) control and (2) ethanol (4.5 g/kg BW). RESULTS: After 6 weeks of treatment, the results revealed a significant increase in isoforms VEGFR1 and VEGFR2 of VEGFR gene expression, significant increases of MMP2 and MMP9 activities, as well as significant decrease of nephrin and podocin gene expressions in the ethanol group, compared with that in the control group. CONCLUSION: These findings indicate that ethanol-induced kidney abnormalities may be in part associated with alteration in expressions of VEGFRs, nephrin, and podocin and in increasing activities of MMP2 and MMP9 as key molecular mediators in the kidney function.