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Background: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation., Methods and Results: Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis., Conclusions: Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Peroxiredoxin I (Prx I) plays a role in regulating macrophage proinflammatory cytokine production and gene expression and participates in immune regulation. However, the possible protective role of Prx I in endotoxin‑induced lethal shock is poorly understood. In the present study, western blot analysis, ELISA and haematoxylin and eosin staining were performed to examine the protein expression of cytoines and analyses the levels of cytokines in the serum and tissue to evaluate the tissue damage. The present study revealed that lipopolysaccharide (LPS)‑induced lethality in Prx I‑/‑ mice was is accelerated via the observed decreased serum IL‑10 levels. Results also demonstrated rapid immune cell infiltration and oxidative stress in the Prx I‑/‑mice liver after LPS injections. These phenomena increased liver apoptosis through increasing cleaved caspase‑3 protein expression in Prx I‑/‑ mice after LPS injections, resulting in high lethality after LPS challenges. These findings provide a new insight for understanding the function of Prx I against endotoxin‑induced injury.

Objective: To investigate the intervention effect of aqueous fractions from Boschniakia rossica (BRAF) on hepatic oxidative stress in mice with liver injury induced by carbon tetrachloride (CCl4)., Method: The experimental mice were randomly assigned into the normal control group, the model group, the silymarin (positive control) group, as well as high and low dose BRAF groups. Mice were treated intragastrically with silymarin or BRAF once every day for 7 days. At the end of the experiment, CCl4 was injected intraperitoneally into the mice to establish the acute liver injury model. The pathological changes was detected with hematoxylin and eosin (HE) staining, and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), superoxide dismutase (SOD) , catalase (CAT), glutathione peroxidase (GPx), Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, and the contents of reduced glutathione (GSH) and malondialdehyde (MDA) were detected by the colorimetric method., Result: BRAF significantly reduced ALT, AST and ALP activities in serum, alleviated hepatic injury induced by CCl4, increased SOD, CAT, GPx and GSH levels in liver, and SOD, Na + -K + -ATPase and Ca2+ -Mg2 + -ATPase activities in liver mitochondria, and decreased the MDA content in liver and liver mitochondria., Conclusion: BRAF reduces hepatic oxidative stress in mice with acute liver injury induced by CCl4, thereby showing the protective effect on mice with acute liver injury induced by CCl4.

Objective: To evaluate whether the antioxidant vitamin E can prevent the harmful effects of reactive oxidative stress (ROS) that occur during compensatory testicular hypertrophy (CTH)., Materials and Methods: Thirty Sprague-Dawley rats were divided into six equal groups: neonatal hemicastrated vitamin E (NH_Vit E/NH) and sham surgical controls (NC), and pubertal hemicastrated vitamin E (PH_Vit E/PH) and sham surgical controls (PC). Vitamin E was administered orally to the NH_Vit E and PH_Vit E groups three times a week from week 3-12 prior to sacrifice. Antioxidant enzymes were measured in testis samples from each animal., Results: Differences in superoxide dismutase activity were observed between the NH (21.04 ± 0.48) and NH_Vit E (22.62 ± 0.64) groups (P = 0.008); the PH (20.59 ± 0.11) and PC (20.91 ± 0.20) groups (P = 0.032); and the PH (20.59 ± 0.11) and PH_Vit E (22.32 ± 1.01) groups (P = 0.008). Thiobarbituric acid-reactive substance in the PH and PH_Vit E groups was 0.097 ± 0.022 and 0.036 ± 0.004 (P = 0.008), respectively; and in the NH and NH_Vit E groups it was 0.135 ± 0.02 and 0.039 ± 0.003 (P = 0.008), respectively., Conclusions: These results suggest that CTH is not associated with reducing oxidative injury, nor does it prevent ROS-induced cell damage. However, administration of vitamin E does reduce oxidative injury and prevent ROS-induced cell damage in a hemicastrated rat model., (Copyright © 2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

2,3,7,8-Tedtrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic endocrine disruptors and has been reported to induce oxidative stress in the reproductive organs. However, the mechanism by which TCDD induces oxidative stress is unclear. The aim of this study is to examine the role of the general cytokine, TGF-beta1, in TCDD-induced oxidative stress in the male reproductive system. To examine the effect of TCDD on antioxidant enzyme activity, we administered TCDD orally to C57BL/6 mice at 1 microgkg/day for 4 days. Using Smad2-siRNA, we examined the involvement of Smad and non-Smad pathways in TCDD-induced oxidative stress. We also measured the mRNA levels of typical antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and analyzed the activation of TGF-beta1, and the downstream signals, Smad2, Smad4, transcription factors (c-Jun, ATF3), and three major MAPKs (JNK, ERK, p38). After TCDD treatment, the mRNA levels of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) were significantly decreased. In addition, TGF-beta1 activity increased and the receptor-activated protein, Smad2, was activated while Smad4 was not. The levels of major transcription factors, c-Jun and ATF3, and the regulator of these transcription factors, MAPK, were also increased by TCDD administration. The mRNA levels of the 3 antioxidant enzymes in the Smad2-siRNA and TCDD co-treated group were higher than that of the TCDD-only treated group but still decreased when compared to control. C-Jun and ATF3 levels were also increased in Smad2-siRNA and TCDD co-treated testes compared to control. However, the levels of c-Jun and ATF3 were lower than those in the group treated with TCDD only. Of the three MAPKs which showed increase in expression after TCDD treatment, p38 was the only one that showed a decrease with Smad2 inhibition, while both ERK and JNK expression were unaffected. In conclusion, we found that the activated TGF-beta1-Smad pathway is involved in TCDD-induced oxidative stress. Furthermore, the effects of TCDD on the testes are caused by the coordinated action of both Smad and non-Smad pathways.

Background: Neurodegenerative diseases are increasingly recognized for their association with oxidative stress, which leads to progressive dysfunction and loss of neurons, manifesting in cognitive and motor impairments. This study aimed to elucidate the neuroprotective role of peroxiredoxin II (Prx II) in counteracting oxidative stress-induced mitochondrial damage, a key pathological feature of neurodegeneration. Methods: We investigated the impact of Prx II deficiency on endoplasmic reticulum stress and mitochondrial dysfunction using HT22 cell models with knocked down and overexpressed Prx II. We observed alcohol-treated HT22 cells using transmission electron microscopy and monitored changes in the length of mitochondria-associated endoplasmic reticulum membranes and their contact with endoplasmic reticulum mitochondria contact sites (EMCSs). Additionally, RNA sequencing and bioinformatic analysis were conducted to identify the role of Prx II in regulating mitochondrial transport and the formation of EMCSs. Results: Our results indicated that Prx II preserves mitochondrial integrity by facilitating the formation of EMCSs, which are essential for maintaining mitochondrial Ca2+ homeostasis and preventing mitochondria-dependent apoptosis. Further, we identified a novel regulatory axis involving Prx II, the transcription factor ATF3, and miR-181b-5p, which collectively modulate the expression of Armcx3, a protein implicated in mitochondrial transport. Our findings underscore the significance of Prx II in protecting neuronal cells from alcohol-induced oxidative damage and suggest that modulating the Prx II-ATF3-miR-181b-5p pathway may offer a promising therapeutic strategy against neurodegenerative diseases. Conclusions: This study not only expands our understanding of the cytoprotective mechanisms of Prx II but also offers necessary data for developing targeted interventions to bolster mitochondrial resilience in neurodegenerative conditions. [ABSTRACT FROM AUTHOR]