Physiology and Pharmacology
Volume:19 Issue: 2, Jun 2015

The purpose of this study was to determine Na-Ca exchanger 2, 3 (NCX2, 3) protein level changes during 2, 5, 10, 15 days after induction of normobaric hyperoxia (HO) preconditioning. Rats were divided in two experimental groups. The first group was exposed to 95% inspired HO for 4 h/day for 6 consecutive days (HO). The second group acted as control, and was exposed to 21% oxygen in the same chamber. Each main group was subdivided to middle cerebral artery occlusion (MCAO-operated) and intact (without any surgery) subgroups. After 2, 5, 10 and 15 days from pretreatment, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 hours reperfusion, neurologic deficit score (NDS) and infarct volume (IV) were measured in MCAO-operated subgroups. The NCX 2, 3 expression levels of core, penumbra and subcortex regions were assessed in sham-operated and intact subgroups. Expression of NCX 2, 3 proteins were increased in penumbra (P=0.000, P=0.002), core (P=0.001, P=0.033) and just NCX3 was increased in subcortex (P=0.033) during preconditioning with HO. Neurologic deficit score and infarct volume were decreased with HO preconditioning. These effects of hyperoxia disappeared gradually during 15 days after pretreatment. Although further studies are needed to clarify the mechanisms of time course of neuroprotection, HO durable effects on NCX2, 3 expression, IV and NDS are consistent with an active role in the genesis of ischemic neuroprotection.

In addition to its antioxidant effect, Vitamin E or α–tocopherol is suggested to enhance remyelination in the animal model of non-inflammatory demyelination. In this study, the possible proliferative effect of vitamin E on human- induced pluripotent stem cell-derived neural progenitors (hiPS-NPs) and the underlying mechanisms were investigated in vitro. NPs were induced from iPS cells via 3 steps within 18 days and then characterized for NPs markers NESTIN, SOX1 and OTX2. MTT assay was used to compare cell populations. LY294002, U0126 and PP2 were used for selective inhibition of enzymes PI3K, MEK and Src-kinase, respectively. Vitamin E increased hiPS-NPs proliferation after 24 and 48 h exposure. The inhibition of both PI3K/Akt and Src-kinase signaling pathways counteracted the effect of vitamin E of NPs. Our data suggest that vitamin E may enhance NPs proliferation via activating PI3K and Src-kinase and may enhance myelin repair following demyelinating Injuries.

17β-Estradiol modulates nociception by binding to the estrogenic receptors and also by allosteric interaction with other membrane-bound receptors like glutamate and GABAA receptors. In addition to its autonomic functions, paragigantocellularis lateralis (LPGi) is involved in the pain modulation, too. The aim of the current study was to investigate the involvement of the membrane-bound GABAA receptors in the pain modulatory effect of intra- LPGi injection of 17β-estradiol of male rats. This study was performed using male Wistar rats in the range of 200-270 g. In order to investigate the antinociceptive effect of intra-LPGi microinjection of 17β-estradiol, cannulation into the LPGi nucleus was performed. 500 nl of drugs were administered 15 minutes prior to formalin injection (50 μl of 4%). Then, formalin-induced paw jerking behaviour was recorded for 60 min. For assessing the role of the GABAA receptors in the estradiol induced pain modulation, 17β-estradiol was administered into the LPGi nucleus 15 min after the injection of 25 ng/μl bicuculline; and paw jerking frequency was recorded for 1 h. The results of the current study showed that intra-LPGi injection of 0.8 μmol of 17β-estradiol attenuated the chronic phase (P<0.001) of paw jerking behaviour. Bicuculine -the GABAA receptor antagonist- significantly reduced the antinociceptive effect of intra-LPGi 17β-estradiol in the chronic phase (P<0.001). It may be concluded that the analgesic effect of intra-LPGi injection of 17β-estradiol on the formalin-induced inflammatory pain might be mediated via GABAA receptors.

Lithium salts are known as effective psychotropic medicine for treatment bipolar disorder and may be used to treat alcoholism, schizoaffective disorders, and cluster headaches. The antioxidant activity and immunomodulatory effects of prospective lithium compounds have been investigated in this work. The antioxidant properties were studied by the voltammetry method. Influence of the lithium compounds on the immune cells of human blood were determined by measuring phagocytic activity of leucocytes and by the rate of blastic transformation of lymphocytes. Relatively better antioxidant and immunotropic properties have been revealed for lithium ascorbate, compare to widely used drug-lithium carbonate. Lithium aspartate revealed antioxidant activity, as well. Studied lithium salts can be considered as prospective psychotropic antioxidant with immunomodulatory effects. The combination of these properties significantly extends the potential medical applications of lithium salts.

Ghrelin is an endogenous peptide that has diverse functions in the body. One of the newly recognized roles of this peptide is its antiapoptotic effect. However, this function has not been investigated in normobaric hypoxia- induced apoptosis in body organs. This study will examine the effect of ghrelin treatment on Bax-Bcl-2 gene expression in the kidney of chronic hypoxic rats. Male Wistar rats in three experimental groups; normal, hypoxic+saline and hypoxic+ghrelin were used in this study. The expression level of Bax and Bcl-2 genes were measured by Real-Time PCR. The Bax/Bcl-2 ratio was also compared in three groups statistically. Chronic hypoxia decreased the Bcl-2 gene expression (p<0.01), and increased the Bax/Bcl-2 ratio (p<0.05). Ghrelin treatment decreased the Bax/Bcl-2 ratio through upregulation of Bcl-2 gene (p<0.05). It seems that ghrelin has an antiapoptotic effect on the kidney of animals that live in a chronic hypoxic state. Which could potentially introduce a therapeutic role for this peptide.

Previous studies have shown that caffeine has beneficial effects on cognitive impairment in sleep deprived male rats. Therefore in the present study, we examined the effects of chronic caffeine administration on learning and memory impairments induced by sleep deprivation (SD) in the intact and ovarectomized (OVX) female rats. Two sets of animals including intact and OVX were randomly recruited into the following subgroups: control, SD, wide platform (Sham platform), caffeine, and caffeine plus SD. Multiple platform method was used for SD induction. Spatial learning and memory were determined using Morris water maze (MWM) task. Throughout behavioral investigation, significant learning impairment was observed in sleep-deprived OVX rats compared to the intact and the other OVX groups (P<0.05). Short term memory impairment was observed in both sleep-deprived OVX and intact groups (P<0.05). 4weeks caffeine administration improved these impairments. Based on these findings we propose that sleep deprivation impaired cognitive function whereas caffeine treatment reversed these impairments.

A large body of evidence points to oxidative stress as prime candidate mediating the behavioral impairments and memory deficits in Alzheimer''s disease (AD). It has been demonstrated that hyperoxia preconditioning activates complex endogenous neuroprotective mechanisms including an increase in capacity of antioxidant defence mechanisms. The aim of this study was to investigate the beneficial effects of normobaric hyperoxia preconditioning in streptozotocin (STZ)- induced memory impairment in rats. Male Wistar rats were first exposed to air with high oxygen concentration (>90%) or atmospheric air for 24 hours and then STZ (3 mg/kg) was bilaterally infused in lateral ventricles of the brain. Two weeks later Morris Water Maze (MWM) test was performed to assess spatial learning and memory consolidation. STZ increased escape latency (P<0.05), distance and number of crossed quadrants (P<0.05) especially on 1st and 2nd days. However, hyperoxia preconditioning significantly attenuated STZ-induced learning and memory deficits during training sessions in the MWM (P<0.05). Preconditioning also increased time spent and swimming distance in the target quadrant in probe test (P<0.05). However, hyperoxia preconditioning had no effect on the swimming speed. Hyperoxia preconditioning significantly attenuated STZ-induced impairments in spatial learning and memory. These results suggest that hyperoxia may have a potential therapeutic effect at the early stage of AD and possibly the prevention of memory deficits.

Silymarine extract is currently prescribed by some physicians for treatment of fatty liver disease. In the present study, the effect of administration of tablet containing silymarine extract on plasma homocysteine (Hcy), folate, vitamin B12 and liver enzymes activity in non-alcoholic steatohepatitis (NASH) was investigated. Seventy-four patients (40 female and 34 male; aged 32-44 years) who were diagnosed with NASH and hyperhomocysteinemic by liver biopsy, measurement of liver enzymes activity and plasma Hcy were recruited for this study. The patients were not consuming alcohol or taking any other medications/medicines. Plasma Hcy, folate, B12, cholesterol, triglyceride, fasting glucose, aspartate aminotransferase (AST) and alaninaminotransferase (ALT) activity of all patients were measured before and after treatment. Tablet containing silymarine extract (140mg∕kg) was administrated thrice /three times a day for 2 months. The results showed a significant reduction in the level of plasma Hcy, cholesterol, triglyceride, fasting glucose (P <0.05) following the administration of tablet containing silymarine extract, however, the increase in plasma folate and B12 levels was not significant. The results did not demonstrate any significant negative correlations between Hcy and B12, and also between Hcy and folate. It can be concluded that consumption of tablet containing silymarine extract in NASH patients significantly reduces level of plasma Hcy, cholesterol, triglyceride, fasting glucose and AST and ALT activity, while level of plasma folate and B12 remained unchanged.