Physiology and Pharmacology
Volume:21 Issue: 2, Jun 2017

Necroptosis, as a novel concept, has been recently introduced in scientific literature. Much of our knowledge about necroptosis comes from ligation of tumor necrosis factor-α to its receptor, TNF receptor 1. Receptor-interacting protein kinase 1, receptor-interacting protein kinase 3 and its substrate, the pseudokinase mixed lineage kinase domain-like protein, have been comprehensively studied as influential components of this process. Emerging pioneering evidence suggests that many molecules, organelles and mechanisms are involved in necroptosis pathway. The aim of this review is presentation of molecular mechanisms of necroptosis in three phases including initiation, regulation and execution of necroptosis. Moreover, this review will summarize unprecedented insights into the contribution of various organelles and cell compartments such as mitochondria, endoplasmic reticulum, nucleus, lysosomes and Golgi apparatus in necroptosis pathway.

Overproduction of gingival pro-inflammatory cytokines have been implicated to play a noticeable role in the pathogenesis of periodontitis, which is characterized by host-mediated destruction of soft and hard periodontal tissues. Moringa oleifera (MO) is a highly valued medicinal plant which has a wide impressive range of traditional medical applications and is an alternative medicine for synthetic drugs which are accompanied with many downsides. The aim of this study was to investigate the effect of administration of the MO extract on gingival levels of TNF-α and IL1-β in the rat periodontal model.
Inflammatory periodontitis was induced using 0-3 ligatures around the neck of right mandibular first molar in male rats. MO leaf extract was solved in dimethyl sulfoxide and injected into the gum tissue directly (500mg/kg) as a pre/post-treatment. Positive control group gave indomethacin (5mg/kg) on a daily basis. Gingival levels of TNF-α and IL1-β were measured using ELISA.
The results of this study revealed that levels of IL1-β and TNF-α increased in the gingival tissue in a model of periodontitis compared to control group (P≤0.001). Also, the results indicated that administration of MO extract could reduce production of TNF-α and IL1-β in the gum tissue of rat periodontal model (P≤0.001). There was no significant difference between MO extract and indomethacin anti-inflammatory effects.
It can be concluded that pre/post-treatment with MO extract due to its direct effect on inhibition of pro-inflammatory cytokines can alleviate inflammatory symptoms in a rat periodontal model.

Recent studies have shown that intermittent normobaric hyperoxia (HO) protects the rat brain from ischemia reperfusion injury. However, the exact mechanism of this kind of protection in vivo is not known. In this study, the effect of HO on expression of TNFR1 and TNFR2 in a stroke model was investigated.
In this experimental study, rats were divided into 4 groups: normoxia – sham, hyperoxia – sham, normoxia – stroke and hyperoxia –stroke for each factor (TNFR1 or TNFR2). Hyperoxia groups were exposed to 95% inspired oxygen for 4 h/day and 6 consecutive days. Oxygen concentration in the control groups was 21% (normoxia, room air). After 24h, the rats were subjected to 60 min of right middle cerebral artery occlusion (MCAO). After 24h reperfusion, neurological deficit scores (NDS) and TNFR1, 2 brain levels using Western Blot were assessed.
Preconditioning with HO decreased NDS. Also, followed by stroke and reperfusion, TNFR1 levels significantly increased; while there was no significant difference in hyperoxia groups compared with normoxia groups in the cortex, HO significantly reduced TNFR1 expression in subcortex. On the other hand, groups of stroke compared to sham groups significantly expressed lower levels of TNFR2 in the cortex and subcortex. There was no significant difference in hyperoxia groups compared with normoxia groups in these areas.
Although additional studies will be required to further elucidate precise mechanisms of ischemic tolerance, it seems that HO is associated with the expression of TNFR1 in subcortex, consistent with an active role in the genesis of ischemic protection.

The aim of present study was to investigate the effects of royal jelly (RJ) on the number of Nissl-stained neurons in caudate putamen unit (CPU) and substantia nigra pars compacta (SNC) and the thickness of gray (TGm) and white matter (TWm) of cerebral and cerebellar cortex in male rats with Parkinson’s disease (PD).
Seventy five Sprague-Dawley adults’ male rats were used. Rats were randomly divided into 5 groups: 1- control intact rats; 2- sham; rats received 0.02% ascorbic acid diluted in saline by CPU injection 3- PD induction without treatment; 4 and 5- PD induction 100 or 200 mg/kg/day RJ for 21 days started 4 weeks after lesion induction. PD induction was carried out by unilateral injection of 6-hydroxydopamine in CPU. The apomorphine were done one week before lesion as well as, second, fourth and seventh weeks after lesion. Nissl-stained neurons of SNC and CPU were counted. The thickness of gray and white matter was measured by histomorphometry.
data showed that RJ has corrected net contralateral turns of PD. RJ at both doses significantly (P Results indicate that RJ can improve PD symptoms; this effect was associated with histomorphometrical disorders.

Previous studies revealed that oxidative stress is elevated in multiple sclerosis (MS). It can harm to biological macromolecules such as DNA. However, the molecular mechanism in protection of genetic information from DNA damages is not clear in MS disease. In this study the expression level of some important genes of OGG1 and MYH involved in base excision repair pathway and, MTH1 and ITPA as main cleaning genes of nucleotide pool from rough nucleotides are examined in MS patients in compared to healthy group.
Peripheral blood mononuclear cells were isolated from relapsing-remitting-MS patients and healthy subjects. After RNA extraction and cDNA synthesis, the expression levels of target genes were examined by RT-qPCR technique.
The level of the MTH1 and MYH genes expression were decreased, but the level of OGG1 mRNA was higher in patients in comparison to the control group. Obtained result did not shown any correlation between expression of examined genes and clinical features of patients such as MS severity and disease duration.
These preliminary results provide more supportive evidences for involvement of oxidative damage and variation in expression of DNA repair genes in MS. Significant increase of OGG1 suggest that the development and progression of pathogenesis in Iranian MS can be related to chronic and direct oxidative damage of genomic DNA not nucleotide pools.

Studies have indicated that diabetes mellitus impairs hippocampus. Diabetes increases the risk of depression and treatment with antidepressants may affect learning and memory. The aim of this study was to evaluate the effects of amitriptyline and fluoxetine on synaptic plasticity and TNF-α level in the hippocampus of streptozotocin-induced diabetic rats.
Experimental groups were control, diabetes, diabetes-amitriptyline and diabetes-fluoxetine (n=8 for each experimental group). Three weeks after the induction of diabetes, the rats received treatment with amitriptyline (5 mg/kg) or fluoxetine (5 mg/kg) for 21 days. Long-term potentiation (LTP) in perforant path-dentate gyrus synapses was assessed (by 400 Hz tetanization) for investigating the effect of treatments on synaptic plasticity. Field excitatory post-synaptic potential indices were measured. Finally, TNF-α levels were measured in hippocampus by enzyme-linked immunosorbant assay.
Six weeks after the diabetes induction, LTP wasn’t different between the control and the diabetes groups and also no significant differences were observed between the diabetes and the diabetes-treated groups; however, amitriptyline and fluoxetine impaired LTP in diabetic rats and there was a significant difference between the control and the diabetes-treated groups. Comparing to the controls, TNF-α level was increased significantly (P Results suggest that amitriptyline and fluoxetine intensify the destructive effects of diabetes on hippocampus and that TNF-α may act as a mediator for these changes; however, other factors may also be involved. Hence, treatment of diabetic patients with antidepressants must be done with extra care.

The 17β-estradiol acts as a neurosteroid in the brain and modulates nociception by binding to the estrogen receptors and also by allosteric interaction with other membrane-bound receptors like glutamate receptors. Paragigantocellularis lateralis nucleus (LPGi) is one of the important brain regions implicated in the pain modulation. So, this study was designed to evaluate the possible involvement of the membrane-bound AMPA receptors of LPGi nucleus in the pain modulatory effect of intra-LPGi 17β-estradiol in the male rats.
In order to study the pain modulatory effect of intra-LPGi microinjection of 17β-estradiol, cannulation into the LPGi nucleus was performed. Then, 500 nl of saline, 17β-estradiol and CNQX- the AMPA receptor antagonist- were unilaterally administered into the right LPGi by injection cannula and Hamilton syringe. In addition, for assessing the role of the AMPA receptors in the pain modulation by 17β-estradiol, 17β-estradiol was injected 15 min after the intra-LPGi administration of CNQX. Then, 50 μl of 4% formalin was subcutaneously injected into the plantar surface of contralateral hind paw and the number of paw jerking behavior was observed for 60 min.
The results showed that intra-LPGi injection of 0.8 μmol of 17β-estradiol attenuated the chronic phase (P Considering the results of this study, it can be concluded that the analgesic effect of intra-LPGi injection of 17β-estradiol might be mediated via AMPA receptors.

Diabetes mellitus, as a chronic metabolic disease, is associated with a wide range of kidney and liver disorders. The goal of this study was to indicate the effects of selenium nanoparticles on the function of kidney and liver enzymes in stereptozocin induced diabetic rats.
In this study, 35 male wistar rats were divided into five groups (n=7): control, diabetic control and three experimental groups receiving selenium nanoparticle solutions at doses of 0.1, 0.2 and 0.4 mg/kg/BW respectively. To induce diabetes in rats, a single dose of streptozocin (60 mg/kg/BW) was injected intraperitoneally. After the experimental period, blood samples were collected from all groups and the blood factors associated with the liver enzymes and kidney factors were measured and analyzed.
The results indicated that the levels of fasting blood sugar in all groups treated with selenium nanoparticles had a significant reduction compared to the diabetic group (P≤0.05). Aspartate amino transferase had a significant reduction at the maximum dose compared to the diabetic group (P≤ 0.05). Also a significant decrease in the level of albumin was seen in the group treated with selenium nanoparticle (P≤ 0.05). Selenium nanoparticle treatment made a significant decreases in the levels of urea and ceratinine at the maximum dose (P≤ 0.05).
The consumption of selenium nanoparticles in proper dosages may have beneficial effects on diabetic complications by lowering blood sugar as well as reducing the increased levels of the liver enzymes and kidney factors, albumin and cratinine resulting in the better function of kidney and liver.

Diabetes is a multifactorial syndrome with high prevalence which may induce serious disorders in the body organs like the liver and kidney. This study aimed to compare the effects of the alcoholic extract of the aerial parts of Swertia longifolia Boiss on blood glucose, lipid profiles and liver and kidney function tests in streptozotocin-induced diabetes.
Thirty five male rats were put into five groups: control, diabetic control and three diabetic experimental groups which were gavaged with alcoholic extract of Swertia longifolia Boiss at doses of 100 and 200 mg/kg BW and glibenclamide at a dose of 10 mg/kg BW, respectively. Diabetes was induced by intraperitoneal injection of streptozotocin. At the end of day 21 blood samples were collected from all groups and the blood factors were measured and analyzed.
The levels of creatinine, urea, liver enzymes, cholesterol and low density lipoprotein increased in the diabetic control group compared to the control, while the mentioned factors in the groups receiving Swertia longifolia Boiss alcoholic extract decreased significantly (P The consumption of the alcoholic extract of the aerial parts of Swertia longifolia Boiss by lowering lipid profiles, liver enzymes, creatinine and urea as well as increasing insulin levels had beneficial effects on the hepatic and renal functions and could alleviate the symptoms of increased glucose and hyperlipidemia in diabetic rats.