Dataset Information

Hesperidin ameliorates hypobaric hypoxia-induced retinal impairment through activation of Nrf2/HO-1 pathway and inhibition of apoptosis.

ABSTRACT: High-altitude retinopathy is initiated by hypobaric hypoxia and characterized by retinal functional changes, but the precise cellular and molecular mechanisms that mediate this dysfunction remain unclear. The aim of our investigation is to determine the protective efficacy of hesperidin (HSD) on the hypobaric hypoxia-induced damage to the retina. Experiment rats were randomly grouped as the control, hypobaric hypoxia group and HSD intervention group. The hypobaric hypoxia and the HSD intervention groups were maintained in a low-pressure oxygen cabin. We found that hypobaric hypoxia dramatically reduced nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) levels, induced an elevation in immunostaining of TUNEL-positive cells. Hypobaric hypoxia exposure resulted in the increase of Bcl-2, decrease of caspase3 and caspase9 expression as well as Bax level. HSD protected the retina from hypobaric hypoxia-caused impairment by enhancing Nrf2 and HO-1 activation, attenuating apoptotic caspases levels, and reducing Bax and preserving Bcl-2 expression. Additionally, oxidative stress increased poly (ADP-ribose) polymerase 1 (PARP1) and suppressed ciliary neurotrophic factor (CNTF) level, HSD treatment reverted this effect by down-regulation of PARP1 and up-regulation of CNTF expression. Taken together, our findings implicate that HSD exerts a protective role in response to hypobaric hypoxia stress by activating Nrf2/HO-1 pathway and inhibiting apoptosis.

SUBMITTER: Xin X

PROVIDER: S-EPMC7655840 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Hesperidin ameliorates hypobaric hypoxia-induced retinal impairment through activation of Nrf2/HO-1 pathway and inhibition of apoptosis.

Xin Xiaorong X Li Yanrong Y Liu Haiping H

Scientific reports 20201110 1

High-altitude retinopathy is initiated by hypobaric hypoxia and characterized by retinal functional changes, but the precise cellular and molecular mechanisms that mediate this dysfunction remain unclear. The aim of our investigation is to determine the protective efficacy of hesperidin (HSD) on the hypobaric hypoxia-induced damage to the retina. Experiment rats were randomly grouped as the control, hypobaric hypoxia group and HSD intervention group. The hypobaric hypoxia and the HSD interventio ...[more]

PMID: 33173100

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Project description:Both hypoxia and inhibition of 2-oxoglutarate dehydrogenase complex (OGDHC) are known to change cellular amino acid pools, but the quantitative comparison of the metabolic and physiological outcomes has not been done. We hypothesize that OGDHC inhibition models metabolic changes caused by hypoxia, as both perturb the respiratory chain function, limiting either the NADH (OGDHC inhibition) or oxygen (hypoxia) supply. In the current study, we quantify the changes in the amino acid metabolism after OGDHC inhibition in the highly sensitive to hypoxia cerebellum and compare them to the earlier characterized changes after acute hypobaric hypoxia. In addition, the associated physiological effects are characterized and compared. A specific OGDHC inhibitor succinyl phosphonate (SP) is shown to act similar to hypoxia, increasing levels of many amino acids in the cerebellum of non-pregnant rats, without affecting those in the pregnant rats. Compared with hypoxia, stronger effects of SP in non-pregnant rats are observed on the levels of cerebellar amino acids, electrocardiography (ECG), and freezing time. In pregnant rats, hypoxia affects ECG and behavior more than SP, although none of the stressors significantly change the levels of cerebellar amino acids. The biochemical differences underlying the different physiological actions of SP and hypoxia are revealed by correlation analysis of the studied parameters. The negative correlations of cerebellar amino acids with OGDHC and/or tryptophan, shown to arise after the action of SP and hypoxia, discriminate the overall metabolic action of the stressors. More negative correlations are induced in the non-pregnant rats by hypoxia, and in the pregnant rats by SP. Thus, our findings indicate that the OGDHC inhibition mimics the action of acute hypobaric hypoxia on the cerebellar amino acid levels, but a better prediction of the physiological outcomes requires assessment of integral network changes, such as increases in the negative correlations among the amino acids, OGDHC, and/or tryptophan.

Dataset Information

Hesperidin ameliorates hypobaric hypoxia-induced retinal impairment through activation of Nrf2/HO-1 pathway and inhibition of apoptosis.

Publications

Hesperidin ameliorates hypobaric hypoxia-induced retinal impairment through activation of Nrf2/HO-1 pathway and inhibition of apoptosis.

Similar Datasets

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