Protective effects of an interaction between vagus nerve and melatonin on gastric ischemia/reperfusion: the role of oxidative stress

Objectives: Vagal pathways in gastrointestinal tract are the most important pathways that regulate ischemia/reperfusion (I/R). Gastrointestinal tract is one of the important sources of melatonin production. The aim of this study was to investigate probable protective effect of the interaction between vagus nerve and melatonin after I/R. Materials and methods: This study was performed in male rats that were divided into six groups. Cervical vagus nerve was cut bilaterally after induction of I/R and the right one was stimulated by stimulator. Melatonin or vehicle was injected intraperitoneally. The stomach was removed for histopathological and biochemical investigations. Results: A significant decrease in infiltration of gastric neutrophils and malondialdehyde (MDA) level after I/R was induced by melatonin and was disappeared after vagotomy. The stimulation of vagus nerve significantly enhanced these effects of melatonin. However, a stimulation of vagus nerve alone increased neutrophils infiltration and MDA level. Melatonin significantly increased the activities of catalase, glutathione peroxidase (GPx), superoxide dismutases (SOD). Unlike stimulation of vagus nerve, vagotomy decreased these effects of melatonin. Conclusion: According to these results, it is probable that protective effects of melatonin after I/R may be mediated by vagus nerve. Therefore, there is an interaction between melatonin and vagus nerve in their protective effects

Mumijo Protection gainst Acetaminophen-Induced Acute Hepatic Injury: Role of Oxidative Stress

Background: A majority of people widely use acetaminophen as a sedative. Overusing the drug for prolonged periods of time can lead to acute liver damage. Mumijo, as a strong antioxidant and anti-inflammatory drug, could possibly reduce some of the acetaminophen-induced side effects on the liver. Thus, the aim of this study is to evaluate the effect of Mumijo on the liver damage caused by the use of acetaminophen. Methods: 40 male Wistar rats were randomly divided into five groups: sham, acetaminophen, low and high doses of mumijo, and vehicle. All groups except the sham group received a single dose of 500 mg/kg acetaminophen via ip injection. Then the groups that were under treatment received 150 mg/kg (low dose) and 250 mg/kg (high dose) of mumijo, and the vehicle group received distilled water as vehicle. After 24 hours, blood samples were taken for biochemical tests, and a part of the liver was extracted for histopathological examination. Results: acetaminophen increases the activities of functional liver enzymes including alanine amino transferase (ALT), aspartate aminotransferase (AST), and gamma glutamine transferase (GGT). In groups under treatment, values of the mentioned enzymes were significantly reduced in comparison with the acetaminophen and vehicle groups (P <0.05), and on the other hand, malondialdehyde (MDA), nitric oxide (NO), and protein carbonyl (PC) increase caused by acetaminophen were reduced by mumijo. Furthermore, the amount of glutathione (GPX) was increased by mumijo (P <0.05). From a histopathological point of view, necrosis and liver damage caused by acetaminophen was decreased by mumijo. Conclusion: The findings showed that mumijo is salient in preventing liver damage caused by consumption of high doses of acetaminophen probably through reducing oxidant activities and also through increasing anti-inflammatory and antioxidant activities

Is genistein neuroprotective in traumatic brain injury?

The concerns about negative consequences of estrogen therapy have led to introduce other strategies to obtain estrogen's benefits in the brain. The present study tests the hypothesis that a major isoflavone of soy; genistein with estrogen-like activity can be neuroprotective in traumatic brain injury (TBI). The maleWistar ratswere randomly divided to four groups: sham, TBI, vehicle and genistein. The TBI was induced byMarmarou method. The brain edema and the disruption of blood–brain-barrier (BBB)were evaluated 48 h post-TBI.Genistein (15mg/kg) or dimethyl sulfoxide (DMSO)was injected i.p., twice after TBI. The intracranial pressure (ICP), the motor performance, and the beam-walk task (WB) were determined before trauma, on trauma day (D0), and first (D1) and second (D2) days post-TBI. Genistein inhibited a development of brain edema and a BBB permeability in TBI animals. An increase of ICP and a defect in motor and WB performance were showed following TBI, in all times evaluated. An increase of ICP induced by TBI was suppressed by genistein on D1 and D2 times. Genistein improved a motor disorder induced by TBI, on D1 and D2 times. Also an increase of traversal time in WB task was suppressed by genistein in TBI animals, on D1 and D2 times. The results of this study demonstrated that genistein can be neuroprotective in TBI. Genistein inhibited the disruption of BBB, the brain edema and the increase of ICP, and the disturbance of neurobehavioral performance in TBI

The role of estrogen and progesterone, administered alone and in combination, in modulating cytokine concentration following traumatic brain injury

Cytokines play an important role in the pathophysiology of traumatic brain injury (TBI). This study was designed to determine the effects of administering progesterone (P) and estrogen (E), alone and in combination, on brain water content, blood–brain barrier (BBB) disturbance, and brain level of cytokines following diffuse TBI. Ovariectomized rats were divided into 9 groups, treated with vehicle, E1, E2, P1, P2, E1+P1, E1+P2, E2+P1, and E2+P2. Levels of BBB disruption (5 h), cytokines, and water content (24 h) were evaluated after TBI induced by the Marmarou method. Physiological (E1 and P1) and pharmacological (E2 and P2) doses of estrogen and progesterone were administered 30 min after TBI. Water content in the E1+P2-treated group was higher than in the E1-treated group. The inhibitory effect of E2 on water content was reduced by adding progesterone. The inhibitory effect of E1 and E2 on Evans blue content was reduced by treatment with E1+P1 and E2+P2, respectively. The brain level of IL-1b was reduced in E1 and E2, after TBI. In the E2+P2-treated group, this level was higher than in the E2-treated group. The brain level of TGF-b was also elevated by the administration of progesterone and estrogen alone, and reduced when the hormones were administered in combination. In conclusion, a combined administration of progesterone and estrogen inhibited the decreasing effects of administration of progesterone and estrogen alone on water content and BBB disruption that mediated to change the proinflammatory cytokines

What are the progesterone-induced changes of the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury patients?

To permit appropriate targeted therapy, the present clinical studywas aimed to investigate the effects of progesterone on the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury (DAI). Forty-eightmaleDAI patients were divided into two groups (control and progesterone). Progesterone group received progesterone in dose of 1 mg/kg per 12 h for five days. The outcome was investigated using Extended Glasgow Outcome Scale (GOS-E) and functional independencemeasure (FIM). Themarkers of inflammation [interleukin-1β (IL-1β), IL-6, transforming growth factor-β1 (TGF-β1)], injury (brain protein of S-100B), and oxidant activity [malondialdehyde (MDA)] were evaluated in the serum of the patients. Higher GOS-E and FIMscoreswere observed in progesterone group at the six-month follow-up (P b 0.05 and P b 0.01, respectively). Meanwhile, a reduction in the serum levels of IL-1β, MDA and S-100B was noticed in progesterone group 24 h after injury (P b 0.05, P b 0.001 and P b 0.05, respectively), and there was an increase in serum levels of IL-6 and TGF-β1 (P b 0.01 and P b 0.05, respectively). Also, lower levels of MDA and S-100B, and higher levels of TGF-β1were observed in progesterone group six days after injury (P b 0.05). According to these findings, progesterone may improve the outcome in DAI patients probably through modulation in the levels of cytokines, and reduction in the injury and oxidant activity