OBJECTIVE: Exploring the changes in cerebellar ferroptosis in hypertensive mice after lead exposure.
METHODS: Twenty-five healthy C57 male mice were selected to construct a hypertensive model by intraperitoneal injection of angiotensin II(Ang II) at a concentration of 0.05 mg/kg for 7 consecutive days. After a systolic blood pressure of 140 mmHg, 20 hypertensive mice were randomly divided into a hypertensive control group and a hypertensive lead exposure group. Twenty C57 mice with normal blood pressure were randomly divided into a blood pressure normal control group and a blood pressure normal lead exposure group. The mice in the normal blood pressure control group and the hypertensive control group drank water freely. Mice in the lead exposure group with normal blood pressure and the lead exposure group with hypertension drank lead acetate water containing 250 mg/L. Ang II was injected intraperitoneally every two days in the hypertensive control group and hypertensive lead exposed group mice. Each group of mice was poisoned for 12 weeks. Using open field experiments and balance beam experiments to detect motor dysfunction in mice. Using a reagent kit to detect the levels of divalent iron(Fe~(2+)), malondialdehyde(MDA), and glutathione(GSH) in the cerebellum of different groups of mice. Western blot was used to determine the protein expression of member 11 of the solute carrier family 7(SLC7A11), glutathione peroxidase 4(GPX4), nuclear receptor coactivator 4(NCOA4), microtubule associated protein 1 light chain 3B(LC3B), and ferritin heavy chain 1(FTH1) in mouse cerebellar tissue.
RESULTS: The result of the open field experiment showed that the activity distance(1013.04 cm) of mice in the hypertensive lead exposure group was significantly lower than that of the hypertensive control group(1351.18 cm) and the lead exposure group with normal blood pressure(1287.35 cm). And the lead exposure group with hypertension also extended the time through the balance beam, which was 29.40 seconds(P<0.05). In addition, the Fe~(2+)content in the cerebellum of mice in the hypertensive lead exposure group was 3.33 μmol/g prot, which was 1.54 times that of the hypertensive control group and 1.14 times that of the lead exposure group with normal blood pressure. The MDA content was 4.71 nmol/mg prot, higher than that of the hypertensive control group and the lead exposure group with normal blood pressure. The GSH content was 5.36 μmol/g prot, lower than that of the hypertensive control group and the lead exposure group with normal blood pressure(P<0.05). Western blot result showed that compared with the hypertensive control group and the lead exposure group with normal blood pressure, the protein expression of SLC7A11 and GPX4 in the hypertensive lead exposure group was significantly reduced(P<0.05). In addition, compared with the control group with normal blood pressure, the expression of NCOA4 and LC3B proteins in the cerebellum of mice in the hypertension control group and lead exposure group with normal blood pressure increased, while the expression of FTH1 protein decreased(P<0.05). The expression of NCOA4 and LC3B proteins in the hypertensive lead exposure group was higher than that in the hypertensive control group and the lead exposure group with normal blood pressure, while the expression of FTH1 protein decreased(P<0.05).
CONCLUSIONS: Lead exposure can exacerbate iron death in the cerebellar tissue of hypertensive mice, and iron autophagy may be involved in its occurrence and development.

Oxaliplatin (OXA) as the platinum-based agent induces the cumulative neuropathy including functional impairment and neuropathic pain. OXA treatment triggered oxidative stress and inflammatory reaction in the spinal cord. Puerarin as a natural product has the neuroprotective effect on neuropathic pain. Hence, the roles and mechanisms of Pue on OXA induced neuropathic pain were studied. In this study, OXA-induced neuropathic pain mouse model was constructed by oxaliplatin injection for 5 consecutive days and two cycles. Pue (10 mg/kg) was administered intraperitoneally for seven consecutive days. The changes of behavior, morphology and levels of related proteins were detected. As a result, OXA-induced mice exhibited as the increased pain hypersensitivity, the impaired motor coordination, the activated NLRP3 inflammasome mediated inflammation and the suppressed nuclear factor erythroid 2-related factor 2 (Nrf2) mediated antioxidative reaction in the spinal cord (P<0.05 vs Control). After Pue administration, the mechanical pain threshold, thermal pain latency, spontaneous pain number and motor latency were improved (P<0.05 vs OXA). In the spinal cord, Pue administration reduced the levels of inflammatory elements, increased the levels of antioxidative elements and decreased the levels of oxidative factors (P<0.05 vs OXA). Furthermore, Pue also bind with Nrf2 and increased the association of Nrf2 to glutathione peroxidase 4 (GPX4). In summary, Pue alleviates oxaliplatin induced neuropathic pain by enhancing Nrf2/GPX4-mediated antioxidant response and suppressing inflammatory reaction in the spinal cord.

Context The overproduction of reactive oxygen species (ROS) during in vitro culture of ovarian tissues impairs follicular development and survival. Aims To evaluate the effects of punicalagin on the development and survival of primordial follicles, stromal cell and collagen fibres, as well as on the levels of mRNA for nuclear factor erythroid 2-related factor 2 (NRF2 ), superoxide dismutase 1 (SOD1 ), catalase (CAT ), glutathione peroxidase 1 (GPX1 ) and perirredoxin 6 (PRDX6 ), and activity of antioxidant enzymes in cultured bovine ovarian tissues. Methods Bovine ovarian cortical tissues were cultured for 6days in α-MEM+ alone or with 1.0, 10.0, or 100.0μM punicalagin at 38.5°C with 5% CO2 . Follicle morphology and growth, stromal cell density, and collagen fibres were evaluated by classical histology, while the expression of mRNA was evaluated by real-time PCR. The activity of enzymes was analysed by the Bradford method. Key results Punicalagin improved follicle survival and development, reduced mRNA expression for SOD1 and CAT , but did not influence stromal cells or collagen fibres. Punicalagin (10.0μM) increased the levels of thiol and activity of SOD1, CAT , and GPX1 enzymes. Conclusions Punicalagin (10.0μM) promotes follicle survival and development and activates SOD1, CAT , and GPX1 enzymes in bovine ovarian tissues. Implications Punicalagin improves follicle development and survival in cultured ovarian tissues.

OBJECTIVE:  This study aimed to investigate the possible positive effects of arbutin in a trinitrobenzene sulfonic acid (TNBS)- induced experimental colitis model, to compare it with mesalazine, which is used in treating inflammatory bowel disease and to observe the effect of its concomitant use.
METHODS:  Forty Wistar albino species male rats were randomized into 5 groups as control, colitis, colitis+arbutin (Arb), colitis+mesalazine (Mes), and colitis+mesalazine+arbutin (M+A). Proinflammatory cytokines [interleukin (IL)-6, IL-1β, tumor necrosis factor alpha (TNF-α)] and oxidant/antioxidant parameters [malondialdehyde (MDA), superoxide dismutase inhibition (SOD) inhibition, myeloperoxidase (MPO), and catalase, glutathione peroxidase (GPx)] were processed from the samples. Histopathological evaluation evaluated goblet cell reduction, cellular infiltration, and mucosal loss.
RESULTS:  When the treatment groups and the TNBS group were compared, statistical significance was achieved in MDA, MPO, SOD inhibition, GPx values, IL-6, IL-1β and TNF-α levels. Histopathological evaluation revealed a statistically significant decrease in the mucosal loss value in the group where mesalazine and arbutin were used together compared to the TNBS group.
CONCLUSIONS:  Our study\'s results elaborated that using arbutin alone or in combination with mesalazine produced positive effects in colitis-induced rats.

The most abundant tripeptide-glutathione (GSH)-and the major GSH-related enzymes-glutathione peroxidases (GPxs) and glutathione S-transferases (GSTs)-are highly significant in the regulation of tumor cell viability, initiation of tumor development, its progression, and drug resistance. The high level of GSH synthesis in different cancer types depends not only on the increasing expression of the key enzymes of the γ-glutamyl cycle but also on the changes in transport velocity of its precursor amino acids. The ability of GPxs to reduce hydroperoxides is used for cellular viability, and each member of the GPx family has a different mechanism of action and site for maintaining redox balance. GSTs not only catalyze the conjugation of GSH to electrophilic substances and the reduction of organic hydroperoxides but also take part in the regulation of cellular signaling pathways. By catalyzing the S-glutathionylation of key target proteins, GSTs are involved in the regulation of major cellular processes, including metabolism (e.g., glycolysis and the PPP), signal transduction, transcription regulation, and the development of resistance to anticancer drugs. In this review, recent findings in GSH synthesis, the roles and functions of GPxs, and GST isoforms in cancer development are discussed, along with the search for GST and GPx inhibitors for cancer treatment.

Plant glutathione peroxidases (GPXs) are important enzymes for removing reactive oxygen species in plant cells and are closely related to the stress resistance of plants. This study identified the GPX gene family members of pepper (Capsicum annuum L.), \"CM333\", at the whole-genome level to clarify their expression patterns and enzyme activity changes under abiotic stress and ABA treatment. The results showed that eight CaGPX genes were unevenly distributed across four chromosomes and one scaffold of the pepper genome, and their protein sequences had Cys residues typical of the plant GPX domains. The analysis of collinearity, phylogenetic tree, gene structure, and conserved motifs indicated that the CaGPX gene sequence is conserved, structurally similar, and more closely related to the sequence structure of Arabidopsis. Meanwhile, many cis elements involved in stress, hormones, development, and light response were found in the promoter region of the CaGPX gene. In addition, CaGPX1/4 and CaGPX6 were basically expressed in all tissues, and their expression levels were significantly upregulated under abiotic stress and ABA treatment. Subcellular localization showed that CaGPX1 and CaGPX4 are localized in chloroplasts. Additionally, the variations in glutathione peroxidase activity (GSH-Px) mostly agreed with the variations in gene expression. In summary, the CaGPXs gene may play an important role in the development of peppers and their response to abiotic stress and hormones.

The exopolymer (ESPp) was obtained from Bacillus licheniformis IDN-EC, composed of a polyglutamic acid and polyglycerol phosphate chain O-substituted with αGal moieties (αGal/αGlcNH2 3:1 molar ratio) and with a 5000 Da molecular weight. The cytotoxicity activity of EPSp was determined by reducing the MTT (3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide) to formazan on HeLa cells. This EPS did not show cytotoxicity against the tested cell line. The ESPp presented great advantages as an antioxidant with free radical scavenging activities (1,1-diphenyl-2-picryl-hydrazyl radical (DPPH),hydroxyl radical (OH), and superoxide anion (O2-)) (65 ± 1.2%, 98.7 ± 1.9%, and 97 ± 1.7%), respectively. Moreover, EPSp increased the enzyme activity for catalase (CAT) and glutathione peroxidase (GSH-Px) in HeLa cells (CAT, 2.6 ± 0.24 U/mL; and GSH-Px, 0.75 ± 0.3 U/L). The presence of ESPp showed a significant protective effect against H2O2 in the cell line studied, showing great viability (91.8 ± 2.8, 89.9 ± 2.9, and 93.5 ± 3.6%). The EPSp presented good emulsifying activity, only for vegetable oils, olive oil (50 ± 2.1%) and sesame (72 ± 3%). Sesame was effective compared to commercials products, Triton X-100 (52.38 ± 1.6%), Tween 20 (14.29 ± 1.1%), and sodium dodecyl sulphate (SDS) (52.63 ± 1.6%). Furthermore, the EPS produced at 0.6 M has potential for environmental applications, such as the removal of hazardous materials by emulsification whilst resulting in positive health effects such as antioxidant activity and non-toxicity. EPSp is presented as a good exopolysaccharide for various applications.

Male infertility represents a significant public health concern. There is a negative impact of inflammatory bowel diseases (IBDs) on the male reproductive system. The aim of this study was to investigate whether oat beta-glucan (OBG) with different molar mass can modulate parameters of antioxidant defense and inflammatory response in the testes of adult Sprague-Dawley rats with TNBS-induced colitis and whether the OBG intervention can modulate the inflammatory response in association with the RAS system. Results: higher testicular superoxide dismutase (SOD), glutathione reductase (GR) activities and glutathione (GSH) concentration, and lower testosterone (T) level and glutathione peroxidase (GPx) activity, were observed in rats with colitis than in healthy control ones. TNBS-induced colitis resulted in decreased the angiotensin 1-7 (ANG 1-7) level in the testes of rats fed with low-molar mass OBG compared to control animals. Conclusions: although colitis induced moderate pro-oxidant changes in the gonads, it seems plausible that dietary intervention with different fractions of oat beta-glucans mass may support the maintenance of reproductive homeostasis via the stimulation of the local antioxidant defense system.

Type 2 diabetes and depression co-occur in a bidirectional manner. Curcumin supplements exhibit antidepressant effects that may mitigate depression by modulating neurotransmitters and reducing inflammatory and oxidative stress pathways. This study aimed to evaluate the efficacy of curcumin in improving depression severity in obese type 2 diabetes patients. The study employed a randomized, double-blind, placebo-controlled trial design with 227 participants. The primary end-point was depression severity assessed using the Patient Health Questionnaire-9. Biomarkers were measured at baseline and at 3-, 6-, 9-, and 12-month intervals. The biomarkers assessed were serotonin levels, pro-inflammatory cytokines (interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha), antioxidant activities (total antioxidant status, glutathione peroxidase, and superoxide dismutase), and malondialdehyde. After 12 months, the curcumin group exhibited significantly improved depression severity (p = 0.000001). The curcumin group had higher levels of serotonin (p < 0.0001) but lower levels of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha (p < 0.001 for all) than the placebo group. Total antioxidant status, glutathione peroxidase activity, and superoxide dismutase activity were elevated in the curcumin group, whereas malondialdehyde levels were greater in the placebo group (p < 0.001 for all). These findings suggest curcumin may have antidepressant effects on obese type 2 diabetes patients.

Testicular torsion is a common disorder in males and results in blockage of testicular circulation with subsequent damage of testicular germ cells. The current work aimed to compare the therapeutic effect of platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) on torsion/detorsion (T/D) injury in rats. Forty mature male Wister rats were arranged into 4 groups; (1) Control, (2) T/D, (3) T/D + PRP, and (4) T/D+ i-PRF. The right testis was twisting 1080° clockwise for 3 h in groups 2, 3 and 4, then 10 μl of PRP or i-PRF was injected intra-testicular 3 h after detorsion in groups 3 and 4, respectively. After 30 days postoperatively, the semen quality and hormonal assay were improved in PRP and i-PRF-treated groups with superiority of i-PRF (P < 0.001). High significance of Catalase, Glutathione Peroxidase (GPx), Superoxide Dismutase, Interleukin-1β (IL-1β), Caspase-3 and Tumor necrosis factor-α (TNF-α) was reported in treated rats with PRP and i-PRF (P < 0.001) with superiority to i-PRF-treated rats (P < 0.001). Testicular histoarchitectures were improved in PRP and i-PRF-treated rats with superiority of i-PRF-treated rats. It was concluded that PRP and i-PRF have regenerative efficacy on testicular damage after induced T/D injury with a superior efficacy of i-PRF.