Evaluation of the protective effect of curcumin on encephalopathy caused by intrahepatic and extrahepatic damage in male rats.

OBJECTIVES: Along with increased intracranial pressure (ICP) and brain damage, brain edema is the most common cause of death in patients with hepatic encephalopathy. Curcumin can pass the blood-brain barrier and possesses anti-inflammatory and anti-oxidant properties. This study focuses on the curcumin protective effect on intrahepatic and extrahepatic damage in the brain. MATERIALS AND METHODS: One hundred and forty-four male Albino N-Mary rats were randomly divided into 2 main groups: intrahepatic injury group and extrahepatic cholestasis group. In intra-hepatic injury group intrahepatic damage was induced by intraperitoneal (IP) injection of acetaminophen (500 mg/kg) [19] and included four subgroups: 1. Sham, 2. Acetaminophen (APAP), 3. Normal saline (Veh) which was used as curcumin solvent, and 4. Curcumin (CMN). In extrahepatic cholestasis group intrahepatic damage was caused by common bile duct litigation (BDL) and included four subgroups: 1. Sham, 2. BDL, 3. Vehicle (Veh), and 4. Curcumin (CMN). In both groups, 72 hr after induction of cholestasis, brain water content, blood-brain barrier permeability, serum ammonia, and histopathological indicators were examined and ICP was measured every 24 hr for three days. RESULTS: The results showed that curcumin reduced brain edema, ICP, serum ammonia, and blood-brain barrier permeability after extrahepatic and intrahepatic damage. The maximum effect of curcumin on ICP was observed 72 hr after the injection. CONCLUSION: According to our findings, it seems that curcumin is an effective therapeutic intervention for treating encephalopathy caused by extrahepatic and intrahepatic damage.

Protective effect of Mumiju against acetic acid-induced ulcerative colitis in rats.

OBJECTIVE: In this study, we elucidated the ameliorative effect of aqueous extract of leaves of Mumiju against acetic acid-induced experimental colitis in male rats. MATERIALS AND METHODS: The animals were randomly divided into four groups (n=7) including I: control group, II: vehicle group (injected with 2 ml acetic acid (4%) intra rectally), III and IV: treatment groups which received Mumiju (250 mg/kg) orally or intraperitoneally for 4 consecutive days after ulcer induction. Ulcer index, severity of inflammation, colonic levels of superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA), and histological changes were recorded after the treatment regimen of 4 days. RESULTS: The ulcer index, severity of inflammation and colonic MDA levels were increased following intrarectal instillation of acetic acid. Also, acetic acid significantly decreased the SOD and GSH levels. Treatment with Mumiju for 4 days exhibited significantly lowered oxidative stress, while elevated of SOD and GSH levels. Regenerative-healing patterns also was seen by histopathological findings after treatment with Mumiju. CONCLUSION: The present investigation demonstrates that Mumiju could be regarded as a herb with potent therapeutic value in the amelioration of experimental colitis in laboratory animals by modulation of oxidant- antioxidant system.

Role of melatonin receptors in the effect of estrogen on brain edema, intracranial pressure and expression of aquaporin 4 after traumatic brain injury.

OBJECTIVES: Traumatic brain injury (TBI) is one of the most common causes of death and disability in modern societies. The role of steroids and melatonin is recognized as a neuroprotective factor in traumatic injuries. This study examined the role of melatonin receptors in the neuroprotective effects of estrogen. MATERIALS AND METHODS: Seventy female ovariectomized Wistar rats were divided into five groups and two subgroups. All animals underwent brain trauma. The groups were as follow: 1) trauma, 2) melatonin receptor antagonist vehicle + estrogen, 3) MT1 melatonin receptor antagonist + estrogen, 4) MT2 melatonin receptor antagonist+ estrogen, 5) MT3 melatonin receptor antagonist+ estrogen. Brain edema (24 hr), intracranial pressure (ICP) (-1, 0, 1, 4 and 24 hr) and blood-brain barrier (BBB) permeability (5 hr) and aquaporin (AQP4) expression (24 hr) were evaluated after TBI. RESULTS: MT1, MT2 and MT3 melatonin receptors had anti-edema effects while MT1 and MT2 have a role in protecting BBB by estrogen. Furthermore, the activity of MT3 and MT2 melatonin receptors weakened the effect of estrogen on ICP. However, melatonin receptors had no role in the effect of estrogen on AQP4 protein. CONCLUSION: Based on the above results, it seems that melatonin receptors appear to influence the effect of estrogen in TBI without altering AQP4 expression. The role of the receptors is different in this interaction.

Does the administration of melatonin during post-traumatic brain injury affect cytokine levels?

Increased levels of inflammatory cytokines after traumatic brain injury (TBI) can lead to brain edema and neuronal death. In this study, the effect of melatonin on pro-inflammatory (IL-1ß, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokines following TBI was investigated considering anti-inflammatory effect of melatonin. Male Wistar rats were divided into five groups: Sham, TBI, TBI + VEH (vehicle), TBI + 5 mg dose of melatonin (MEL5), TBI + 20 mg dose of melatonin (MEL20). Diffuse TBI was induced by Marmarou method. Melatonin was administered 1, 24, 48 and 72 h after TBI through i.p. Brain water content and brain levels of pro-inflammatory (IL-1ß, IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines were measured 72 h after TBI. The IL-1ß levels decreased in the TBI + MEL5 and TBI + MEL20 groups in comparison to TBI + VEH group (p < 0.001). The levels of IL-6 and TNF-α also decreased in melatonin-treated groups compared to control group (p < 0.001). The amount of IL-10 decreased after TBI. But melatonin administration increased the IL-10 levels in comparison with TBI + VEH group (p < 0.001). The results showed that melatonin administration affected the brain levels of pro-inflammatory and anti-inflammatory cytokines involving in brain edema led to neuronal protection after TBI.

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.