Effects of GIT-27NO, a NO-donating compound, on hepatic ischemia/reperfusion injury

Mangano, Katia; Lanteri, Raffaele; Basile, Maria Sofia; Bellavia, N.; Latino, Rosalia; Messina, D; Fagone, Paolo; Colletti, Giuseppe; Nania, Riccardo; Caltabiano, Rosario; Marco, Roberto Di; Cataldo, Antonio Di

doi:10.1177/2058738419862736

Cited by 3 publications

(2 citation statements)

References 51 publications

(109 reference statements)

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“…In addition, we also evaluated the transcriptomic analysis of MIF, DDT and their receptors in the brains of a mouse model of alcoholism. This analysis was carried out by DNA microarray analysis that represents a useful in silico toll for the better understanding of pathogenic pathways and the possible prediction of new diagnostic therapeutic approaches in several clinical settings, including immunoinflammatory and autoimmune diseases and fibrotic diseases (45,46,(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59). Our analysis first demonstrated that no differences in the expression of MIF, DDT and their receptors can be found in brains of both rodent models of AUD and patients with this condition.…”

Section: Discussionmentioning

confidence: 83%

Transcriptomic analysis reveals moderate modulation of macrophage migration inhibitory factor superfamily genes in alcohol use disorders

et al. 2020

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Alcohol use disorder (AUD) is a primary, chronic and relapsing disease of brain reward, motivation and memory, which is associated with several comorbidities, including major depression and post-traumatic stress disorder. It has been revealed that Ibudilast (IBUD), a dual inhibitor of phosphodiesterase-4 and-10 and of macrophage migration inhibitory factor (MIF), exerts beneficial effects on AUD in rodent models and human patients. Therefore, IBUD has attracted increasing interest, with research focusing on the elucidation of the pathogenic role of MIF and its homologue, D-dopachrome tautomerase (DDT), in the pathogenesis and maintenance of AUD. By using DNA microarray analysis, the current study performed a transcriptomic expression analysis of MIF, DDT and their co-receptors, including CD74, C-X-C chemokine receptor (CXCR)2, CXCR4 and CXCR7 in patients with AUD. The results revealed that the transcriptomic levels of MIF, DDT and their receptors were superimposable in the prefrontal cortex of rodents and patients with AUD and human patients. Furthermore, peripheral blood cells from heavy drinkers exhibited a moderate increase in MIF and DDT levels, both at the baseline and following exposure to alcohol-associated cues, based on individual situations that included alcohol-related stimuli resulting in subsequent alcohol use (buying alcohol and being at a bar, watching others drink alcohol). Considering the overlapping effects of MIF and DDT, the inverse Fisher's χ 2 test was performed on unadjusted P-values to evaluate the combined effect of MIF and DDT. The results revealed a significant increase in these cytokines in heavy drinkers compared with controls (moderate drinkers). To the best of our knowledge, the present study demonstrated for the first time that MIF and DDT expression was upregulated in the blood of patients with AUD. These results therefore warrant further study to evaluate the role of MIF and DDT in the development and maintenance of AUD, to evaluate their use as biomarkers to predict the psychotherapeutic and pharmacological response of patients with AUD and for use as therapeutic targets.

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Section: Discussionmentioning

confidence: 83%

Transcriptomic analysis reveals moderate modulation of macrophage migration inhibitory factor superfamily genes in alcohol use disorders

et al. 2020

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“…After that, the working solution was diluted with serum‐free DMEM. The cells were pretreated with 10 μM of DMF or 5 μM of ML385, 2 h prior to 1,3‐DCP exposure 46,47 …”

Section: Methodsmentioning

confidence: 99%

1,3‐Dichloro‐2‐propanol induced ferroptosis through Nrf2/ARE signaling pathway in hepatocytes

Guan

Zhang

Meng

et al. 2022

Environmental Toxicology

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1,3-Dichloro-2-propanol (1,3-DCP) is a representative chloropropane environmental contaminant with multiple toxicities. Ferroptosis is a novel iron-dependent form of regulated cell death that is closely associated with the accumulation of lipid peroxides, Fe 2+ and reactive oxygen species (ROS). In this study, we found that 1,3-DCP could induce mouse liver injury via ferroptosis. Administrating of C57BL/6J mice with 12.5, 25, and 50 mg/kg 1,3-DCP for 4 weeks via oral gavage, the data showed that 1,3-DCP exposure led to the pathological changes in mouse livers, remarkably induced accumulation of malondialdehyde (MDA) and Iron, reduction of glutathione (GSH), and changed in the expression of ferroptosis marker proteins glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase-4 (ACSL4). Then, we also proved the results with HepG2 cells in vitro. The data showed that treatment 1,3-DCP significantly triggered the ferroptosis in vitro. Furthermore, we found that the ferroptosisrelated signal pathways were significantly activated in mice livers and HepG2 cells in response to 1,3-DCP exposure. The data showed that 1,3-DCP induced ferroptosis by inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into nuclear and thereby suppressing the expression of its downstream target proteins including GPX4, ferritin heavy chain (FTH), ferroportin (FPN), cystine/glutamate transporter xCT (SLC7A11), and heme oxygenase 1 (HO-1). Taken together, our findings confirmed that 1,3-DCP induced ferroptosis via the Nrf2/ARE signaling pathway in hepatocytes. Our works provide new toxicity mechanisms of 1,3-DCP with ferroptosis on hepatocytes injury.

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Drug delivery nanosystems targeted to hepatic ischemia and reperfusion injury

Ferreira-Silva

Faria-Silva

Baptista

et al. 2021

Drug Deliv. and Transl. Res.

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Effects of GIT-27NO, a NO-donating compound, on hepatic ischemia/reperfusion injury

Cited by 3 publications

References 51 publications

Transcriptomic analysis reveals moderate modulation of macrophage migration inhibitory factor superfamily genes in alcohol use disorders

Transcriptomic analysis reveals moderate modulation of macrophage migration inhibitory factor superfamily genes in alcohol use disorders

1,3‐Dichloro‐2‐propanol induced ferroptosis through Nrf2/ARE signaling pathway in hepatocytes

Drug delivery nanosystems targeted to hepatic ischemia and reperfusion injury

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