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Ghrelin Improves Antioxidant Defense in Blood and Brain in Normobaric Hypoxia in Adult Male Rats.

ABSTRACT: PURPOSE: Hypoxia is one of the important factors in formation of reactive oxygen species (ROS). Ghrelin is a peptide hormone that reduces oxidative stress. However, antioxidant effect of ghrelin on blood and brain in normobaric hypoxia condition has not yet been investigated. METHODS: thirty-two animals were randomly divided into four (n=8) experimental groups: Control (C), ghrelin (Gh), hypoxia (H), hypoxic animals that received ghrelin (H+Gh). Normobaric systemic hypoxia (11% O2) was induced in rats for 48 hours. Effect of ghrelin (80 μg/kg, i.p) on serum TAC and MDA and brain SOD, CAT, GPx and MDA were assessed. RESULTS: Hypoxia significantly (p<0.001) increased both blood and brain MDA Levels. Ghrelin treatment significantly (p<0.001) decreased blood MDA levels both in control and hypoxia, and brain MDA levels in hypoxia conditions. Brain SOD, CAT and GPx variations were not significant in two days of hypoxia. Ghrelin treatment also could not significantly increase activity of SOD, CAT and GPx in brain. Total antioxidant capacity of serum increased in ghrelin treatment both in control and hypoxic conditions, although it was only significant (p<0.01) in control conditions. CONCLUSION: Our findings showed that administration of ghrelin may be useful in reducing blood and brain oxidative stress in normobaric hypoxia condition.

SUBMITTER: Omrani H

PROVIDER: S-EPMC4517091 | biostudies-other | 2015 Jun

REPOSITORIES: biostudies-other

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Ghrelin Improves Antioxidant Defense in Blood and Brain in Normobaric Hypoxia in Adult Male Rats.

Omrani Hasan H Alipour Mohammad Reza MR Mohaddes Gisou G

Advanced pharmaceutical bulletin 20150601 2

<h4>Purpose</h4>Hypoxia is one of the important factors in formation of reactive oxygen species (ROS). Ghrelin is a peptide hormone that reduces oxidative stress. However, antioxidant effect of ghrelin on blood and brain in normobaric hypoxia condition has not yet been investigated.<h4>Methods</h4>thirty-two animals were randomly divided into four (n=8) experimental groups: Control (C), ghrelin (Gh), hypoxia (H), hypoxic animals that received ghrelin (H+Gh). Normobaric systemic hypoxia (11% O2) ...[more]

PMID: 26236669

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Project description:The intensification of oxidative stress and destabilization of the antioxidative defenses of an organism is a consequence of many environmental factors. We considered aspects conditioning male reproductive potential and the functionality of enzymatic antioxidative mechanisms, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), and their correlations with Li, Be, B, Na, Mg, Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Ag, Cd, Sn, Sb, Ba, Hg, Tl, Pb, and malondialdehyde (MDA), as well as genetic polymorphism IL-4v.C589T (rs2243250) in men with infertility (n = 76). A healthy normozoospermic control (n = 87) was also used. We assessed the impact of negative changes driven by oxidative stress on enzymatic antioxidative mechanisms as well as the role of MDA in the overall process. On this basis, we infer connections between disturbances in enzymatic antioxidative defense and reproductive potential. Based on a molecular analysis of the polymorphism of gene IL-4v.C589T (rs2243250) (chromosome 5) (PCR-RFLP), we considered the relationships among particular genotypes with the possibility of occurrence of male infertility. Concentrations of chemical elements were measured in the blood. The activity of antioxidants and MDA levels were measured in serum. In the infertile group, higher GPx activity was noted (6.56 nmoL·min-1·mL-1, control: 4.31 nmoL·min-1·mL-1; p = 0.004), while GR achieved a greater level in the control (17.74 nmoL·min-1·mL-1, infertile: 15.97 nmoL·min-1·mL-1, p = 0.043), which implies diversified efficiency of the first and second lines of defense. The polymorphism of IL-4v.C589T (rs2243250) was not directly connected with infertility because there were not any differences in the frequency of genotypes between the infertile and control group (p = 0.578). An analysis of genotypes CC and TT (polymorphism IL-4v.C589T (rs2243250)) indicated numerous correlations between antioxidants, chemical elements and MDA. Therefore, chemical economy, antioxidative defense and genetic conditions are connected and jointly shape male reproductive potential. Chemical elements influence antioxidative defense and male fertility; the most important modulators appeared to be Na, Ba, Al and B. The polymorphism of gene IL-4v.C589T (rs2243250) has a limited influence on antioxidative defense and the metabolism of chemical elements.

Project description:Background and purposeDamage of the blood-brain barrier (BBB) increases the incidence of neurovascular complications, especially for cerebral hemorrhage after tPA (tissue-type plasminogen activator) therapy. Currently, there is no effective method to evaluate the extent of BBB damage to guide tPA use. Herein, we investigated whether blood levels of tight junction proteins could serve as biomarker of BBB damages in acute ischemic stroke (AIS) in both rats and patients. We examined whether this biomarker could reflect the extent of BBB permeability during cerebral ischemia/reperfusion and the effects of normobaric hyperoxia (NBO) on BBB damage.MethodsRats were exposed to NBO (100% O2) or normoxia (21% O2) during middle cerebral artery occlusion. BBB permeability was determined. Occludin and claudin-5 in blood and cerebromicrovessels were measured. Patients with AIS were assigned to oxygen therapy or room air for 4 hours, and blood occludin and claudin-5 were measured at different time points after stroke.ResultsCerebral ischemia/reperfusion resulted in the degradation of occludin and claudin-5 in microvessels, leading to increased BBB permeability in rats. In blood samples, occludin increased with 4-hour ischemia and remained elevated during reperfusion, correlating well with its loss from ischemic cerebral microvessels. NBO treatment both prevented occludin degradation in microvessels and reduced occludin levels in blood, leading to improved neurological functions in rats. In patients with AIS receiving intravenous tPA thrombolysis, the blood occludin was already elevated when patients arrived at hospital (within 4.5 hours since symptoms appeared) and remained at a high level for 72 hours. NBO significantly lowered the level of blood occludin and improved neurological functions in patients with AIS.ConclusionsBlood occludin may be a clinically viable biomarker for evaluating BBB damage during ischemia/reperfusion. NBO therapy has the potential to reduce blood occludin, protect BBB, and improve outcome in AIS patients with intravenous tPA thrombolysis.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02974283.

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Ghrelin Improves Antioxidant Defense in Blood and Brain in Normobaric Hypoxia in Adult Male Rats.

Publications

Ghrelin Improves Antioxidant Defense in Blood and Brain in Normobaric Hypoxia in Adult Male Rats.

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