Glutathione Peroxidase Research Articles

Investigation and assessment of oxidant – antioxidant status of some enzymes and vitamins in Iraqi patients with chronic myeloid leukemia

Abstract Aim. To investigate and assess the concentrations of glutathione peroxidase, superoxide dismutase, catalase, vitamin A and vitamin C in Iraqi patients infected by chronic myeloid leukemia (CML). Material and methods. Forty-eight Iraqi patients of ages ranged between (15-75) years took part in the current study. Enzymatic antioxidants (Gpx, SOD and CAT) and antioxidant vitamins (A and C) were estimated spectrophotometrically in blood sera of all patients according to age and sex variables, and then all clinical parameters were compared with healthy individuals (control groups). Results. Evaluation of oxidant-antioxidant status. Glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) enzymes concentrations recorded high significant decreasing (***p <0.0001) in blood serum of CML patients according to age and sex factors. Moreover, vitamins A and C showed a high significant decreasing (***p <0.0001) in their concentrations as measured in blood serum of CML patients with diverse ages and sexes. The GPx, SOD, CAT, Vitamin A and Vitamin C in the current study, are considered excellent biochemical markers for following the acuity of CML disease depending on age and sex variables. Conclusion. The clinical significance of oxidative stress represented by lack of enzymes and vitamins in the current study was proven. Statistically significant differences were recorded and observed between patients and control groups depending on age and sex factors.

Asiatic acid induces lung cancer toxicity by triggering SRC-mediated ferroptosis

Ferroptosis is a recently discovered form of regulated cell death that shows promise as a novel approach for inducing tumor cell death in cancer treatment, with significant research potential. Asiatic acid (AA), a key component of the traditional Chinese medicine Centella asiatica, has been identified as having potential therapeutic benefits for various diseases, particularly cancer. Non-small cell lung cancer (NSCLC) is a challenging and prevalent form of cancer to treat. In our study, we utilized network pharmacology, molecular docking, and experimental methods to investigate the potential of AA in treating NSCLC and to elucidate its role in inhibiting cancer through the ferroptosis pathway. Through network pharmacology analysis, we identified that AA targets the core NSCLC protein SRC through the ferroptosis pathway. Our experiments demonstrated that treatment with AA led to increased iron accumulation, mitochondrial membrane potential, and expression of ferroptosis markers glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-CoA synthetase long chain family member 4 (ACSL4) in NSCLC cells, confirming the induction of ferroptosis. In conclusion, AA has the potential to target SRC and induce NSCLC cell death through the ferroptosis pathway, offering a promising approach for cancer treatment.

LFHP-1c improves cognitive function after TBI in mice by reducing oxidative stress through the PGAM5-NRF2-KEAP1 ternary complex

Traumatic brain injury (TBI) is a leading cause of disability and death. Thus, timely and effective secondary brain injury intervention is crucial, with potential to improve the prognosis of TBI. Oxidative stress contributes to post-traumatic secondary cognitive impairment, and the reduction of post-traumatic oxidative stress effectively enhances cognitive function. Phosphoglycerate-mutating enzyme 5 (PGAM5), a member of the phosphoglycerate transporter enzyme family, is upregulated in TBI and induces mitochondrial autophagy. This further exacerbates damage following TBI. The present study focused on the small molecule drug, LFHP-1c, which is a novel inhibitor of PGAM5. The present study used an in vivo mouse model incorporating a controlled cortical impact-induced TBI, to examine the impact of LFHP-1c on oxidative stress and cognitive function. The present study aimed to determine the impact of LFHP-1c on the PGAM5-Kelch-like ECH-associated protein 1 (KEAP1)- nuclear factor erythroid 2-related factor 2 (NRF2) ternary complex within the TBI context. Results of the present study indicated that LFHP-1c suppresses PGAM5 expression and inhibits the development of the PGAM5-KEAP1-NRF2 ternary complex, thereby promoting the release of NRF2 and KEAP1. This in turn promotes the entry of NRF2 into the nucleus following TBI, leading to increased expression of anti-oxidative stress downstream factors, such as heme oxygenase-1, glutathione peroxidase 1 and superoxide dismutase 1. In addition, LFHP-1c also released KEAP1, leading to mitochondrial Rho GTPase 2 degradation and reducing perinuclear aggregation of mitochondria in the cell, which reduced oxidative stress and ultimately improved cognitive function after TBI.

Effects of Chymotrypsin Therapy on Alpha 1-Anti Trypsin and Glutathione Peroxidase in Facial Skin of Rabbits Injected by Hyaluronic Acid

Effects of Chymotrypsin Therapy on Alpha 1-Anti Trypsin and Glutathione Peroxidase in Facial Skin of Rabbits Injected by Hyaluronic Acid

Beneficial effects of Haematococcus pluvialis on growth and hepatopancreas health status in crayfish (Procambarus clarkii) via remodeling the gut microbial metabolic functions

Plant proteins fulfill roles in low-fishmeal diets for crustaceans, but their overuse could have negative effects. Haematococcus pluvialis has the potential to be used as a functional additive due to its high astaxanthin. As such, this study aimed to investigate the effects of dietary H. pluvialis supplementation on growth, hepatopancreas health, and gut metabolic functions in crayfish. 720 crayfish with average weight around 9.20 g were randomized into six treatments (HP0, HP0.3, HP0.6, HP0.9, HP1.2, and HP1.5) in three replications each, and fed six different dosages of H. pluvialis over sixty days. Crayfish exposed to H. pluvialis at concentrations of 0.3, 0.6, and 0.9 % showed significant increases in final average weight, weight gain rate, and specific growth rate (P < 0.05) compared to the HP0 group, together with the highest contents of muscle and shell astaxanthin in the HP0.9 group. Furthermore, increasing H. pluvialis supplementation exhibited the potential to repair hepatopancreas, as demonstrated by the decrease in hemolymph malondialdehyde (MDA) content and activities of alanine aminotransferase and aspartate aminotransferase, as well as the increase in the total protein content, superoxide dismutase, and glutathione peroxidase (GSH-Px) activities. Moreover, high H. pluvialis diets improved microbial dysbiosis by increasing specific microbes, the alpha diversity index, and shifting prominent phyla such as Proteobacteria and Firmicutes. Specifically, dietary H. pluvialis inclusion significantly decreased Vibrio (Proteobacteria) compared to the HP0 group (P < 0.05), but Tyzzerella (Firmicutes) showed the opposite regulatory pattern. A further statistical check revealed that 20 differential OTUs were shared by all H. pluvialis groups compared to the HP0 group, with OTU1439 and OTU2941 identified as the main growth-liver health contributors. Accordingly, high H. pluvialis diets contributed to more complex and stable microbial networks, and down-regulated alanine, aspartate, and glutamate metabolism, as well as lipopolysaccharide biosynthesis. Taken above, the optimal dietary H. pluvialis inclusion level was recommended to be 0.78–0.86 % according to the growth and astaxanthin contents. High H. pluvialis feeding reversed gut microbial dysfunction and improved hepatopancreas antioxidant capacity.

Quantitatively characterize the response of the hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) under elevated temperature stress

Global warming may affect the health of marine species. However, the collected information on quantitative assessment of response in fish under elevated temperature is poorly defined. The present study aimed to quantitatively evaluate the effects of the hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) under elevated temperature (33 °C and 36 °C, ET1 and ET2) stress for 14 days. As endpoints, we examined changes in body growth, hemato-immunological parameters, liver oxidative stress markers, as well as changes of the stomach digestive enzymes. Compared to the control, the body weight was significantly decreased in ET2 group for 14 d exposure, and a remarkable change of differential leukocyte counts of the fish was observed in ET1 group at 3 d and in ET2 group at 14 d. The respiratory burst activity of the hybrid grouper leukocytes markedly decreased in the treatment groups after 14-d exposure. Overall, the antioxidant enzyme activities and transcriptional levels of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GSH-PX) were markedly inhibited in the liver for 3-d and 14-d exposure. The expression levels of nf-κb mRNA were significantly inhibited while the expression levels of atp2b1 mRNA were significantly induced after 14-d exposure. The activities of pepsin and lipase in the stomach were significantly reduced. In addition, an innovative hazard classification system (ET-HCS) was developed to quantitatively characterize the stress response of the fish following elevated temperature treatments. The stress level of ET2 group for 14-d exposure was ranked as level IV (high stress), and the other treatments were ranked as level II (low stress). Taken together, the findings of this study further extend our understanding of quantitative assessment of response in fish under high-temperature stress, which provides valuable information for improving countermeasures of mariculture industry.

Screening high-efficiency promoter to construct trans-vp28 gene Anabaena sp. PCC7120 against white spot syndrome virus of Litopenaeus vannamei

This study aimed to select high-quality promoters to construct trans-vp28 gene Anabaena sp. PCC7120 and feed Litopenaeus vannamei to assess the effect of L.vannamei against white spot syndrome virus (WSSV). Transgenic algae were created using five plasmids containing PrbcL, Pcpc560, Ptrc, Ptac, and PpsbA. According to the gene expression efficiency and the growth index of transgenic algae, Pcpc560 was determined to be the most efficient promoter. Shrimps were continuously fed trans-vp28 gene Anabaena sp. PCC7120 for one week and then challenged with WSSV. After the challenge, the transgenic algae group (vp28-7120 group) was continuously immunized [continuous immunization for 0 days (vp28-7120-0d); continuous immunization for 2 days (vp28-7120-2d); continuous immunization for 4 days (vp28-7120-4d)]. After seven days, the daily survival rate of each experimental group was continuously tracked. Following the viral challenge, the hepatopancreas samples were assayed for their levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), thioredoxin peroxidase (TPX), acid phosphatase (ACP), and alkaline phosphatase (AKP) at varying time intervals. In comparison to the positive control group (challenge and no vaccination) and the wild-type group (challenge, fed wild-type Anabaena sp. PCC7120), the vp28-7120 group (challenge, fed trans-vp28 gene Anabaena sp. PCC7120) exhibited a remarkable increase in survival rates, reaching 50% (vp28-7120-0d), 76.67% (vp28-7120-2d), and 80% (vp28-7120-4d). Furthermore, the vp28-7120 group consistently displayed significantly higher activities of SOD, CAT, GSH-Px, ACP, and AKP, while exhibiting notably lower TPX activity, when compared to the control group. These results indicate that the Pcpc560 promoter effectively elevated the expression level of the exogenous vp28 gene and spurred the growth of the trans-vp28 gene Anabaena sp. PCC7120. Consequently, trans-vp28 gene Anabaena sp. PCC7120 significantly bolstered the immunity of L.vannamei. Therefore, utilizing the Pcpc560 promoter to develop trans-vp28 gene Anabaena sp. PCC7120 based oral vaccine is highly beneficial for industrial-scale cultivation, advancing its commercialization prospects.

Effect of advanced chelate technology-based trace minerals on growth performance, mineral digestibility, tibia properties, and antioxidant status in two broiler strains

This research aimed to assess the impact of diet supplementation of Advanced Chelate Technology-based Mineral (ACTMS), on the Ross and Arian broilers performance. 520 broilers, of two strains, were allocated to 8 treatments (4 for each strain), 5 replicates, (13 chicks/replicate) and reared for 42 days. The treatments include 0 (CONT), 250 (SBC250), 1000 (SBC1000), and 2000 (SBC2000) of ACTMS. Feed intake, weight gain, and feed conversion ratio were recorded, and the European Production Efficiency Factor (EPEF) was also calculated. Serum antibody was measured in response to sheep red blood cell (SRBC) to evaluate humoral immune response. Blood sample and tibia were used to measure the bone composition of Ca and P. No significant difference was obtained in feed intake (P >0.05), however, weight gain, feed conversion ratio, and EPEF showed significant differences (P˂0.05). The results showed that the interaction effect of Ross× SBC250 had the highest average daily feed intake during 25-42 and 0-42 days of age, but Ross×CONT group provided the lowest average daily feed intake (P˂0.05). Furthermore, the Ross×CONT group had the highest average daily gain during 0-10, 25-42, and 0-42 days of age (P<0.05). The Ross×CONT group also provided the best feed conversion ratio during 0-10 days of rearing period compared to other treatments (P<0.05). Various levels of ACTMS, significantly (P˂0.05) enhanced the antioxidant activity of superoxide dismutase and glutathione peroxidase. No significant differences were obtained in blood parameter (P>0.05), though, SBC2000 exhibited the greatest numerical phosphorus content. There was no significant impact of strain effects on blood metabolites, however, the Ross strain exhibited higher values. The results indicated that the Arian× SBC250 group had the largest tibia diameter which had a significant difference from the Arian×CONT group (P<0.05). In conclusion, ACTMS inclusion in the ration (either replacement or on top) led to the significant improvement of FCR and ADWG (SBC250 as on top) and EPEF (SBC2000 replacement) in the Ross strain and some parameters in Arian strains (mostly numerically).

Diagnostic sensitivity and specificity of indicators of glutathione antioxidant system in spermatozoa of infertile men with different forms of pathospermia

Background. One of the most important antioxidant defence mechanism in spermatozoa is the gluthatione system which includes glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and reduced glutathione (GSH). It is promising to use ROC analysis, which allows to assessing the diagnostic sensitivity and specificity of indicators. Materials and methods. Infertile men were divided into 3 groups: patients with oligozoospermia (n = 30), asthenozoospermia (n = 34), and oligoasthenozoospermia (n = 22). To assess the diagnostic sensitivity and specificity of indicators, the values of the biomarkers were tested using the receiver operating characteristic (ROC) curve, and the area under it (AUC), the standard error (SE) and the 95% confidence interval (CI 95%) were calculated. Results. The ROC analysis showed that GP activity was characterized by excellent diagnostic significance for diagnosing both oligozoospermia and asthenozoospermia (the sensitivity was 100%, and specificity – 100%). The GR activity has moderate diagnostic significance, since the AUC is 0.654 (95% CI from 0.503 to 0.785, P = 0.0645) for oligozoospermic, the AUC is 0.612 (95% CI from 0.454 to 0.7555, P = 0.1979) for asthenozoospermic men. The analysis of the ROC curve revealed a good diagnostic value of GsT activity in sperm samples for the diagnosis of pathospermia (sensitivity of 75% and specificity of 80%). Simultaneously, it was shown that GSH content could not serve as valuable biomarkers for distinguishing patients with pathospermia from healthy controls, with an AUC of 0.615, corresponding to moderate diagnostic significance for oligozoospermia. Conclusion. The results of this study show that the cut-off points for the biomar­kers glutathione peroxidase and glutathione-S-transferase can be used to distinguish between patients with pathospermia and normozoospermia, and the parameters themselves can serve as valuable diagnostic biomarkers to distinguish patients with pathospermia from healthy controls, regardless of the causes of pathospermia. The value of these indicators below the cut-off point indicates the probable presence of pathology. Indicators of GR activity and GSH content have a low diagnostic value, which makes them unsuitable for use as laboratory tests for the diagnosis of male infertility.

Effect of Levobupivacaine Hydrochloride-Loaded Nanospheres on Delayed Cerebral Vasospasm Following Subarachnoid Hemorrhage in Rabbits

This research was aimed to analyze the mechanism of action of levobupivacaine hydrochloride-loaded nanospheres on delayed cerebral vasospasm following subarachnoid hemorrhage (SAH). Levobupivacaine hydrochloride-loaded nanospheres (LevoBPV Hcl/PLGA) were prepared using the solvent evaporation methodology, with the raw material as a control. The blood drug concentrations were detected by HPLC after subcutaneous and subarachnoid administration in experimental rabbits. Forty New Zealand white rabbits were randomly assigned into Sham group, SAH group, LevoBPV Hcl group (10 mg/kg), and LevoBPV Hcl/PLGA group (10 mg/kg), with 10 rabbits in each group. The SAH model was induced using the double blood injection methodology combined with internal carotid artery ligation. Brain tissue samples were collected on day 7 for pathological characterization, determination of neuronal apoptosis, and measurement of basilar artery diameter and area. The levels of oxidative stress factors (superoxide (SOD), malondiadehyde (MDA), glutathione peroxidase (GSH-Px)) and vasoconstrictor factors (nitric oxide (NO), endothelin-1 (ET-1)) in the cerebrospinal fluid (CSF) were detected using assay kits. The results revealed that the drug loading capacity of LevoBPV Hcl/PLGA was 29.13%, encapsulation efficiency was 87.09%, and the average particle size was 81.43 μm. Under the same dosage, both subcutaneous and subarachnoid administration of LevoBPV Hcl/PLGA exhibited two concentration peaks in the blood drug concentration, with lower concentration values versus LevoBPV Hcl group, and a longer average residence time than LevoBPV Hcl group (P &lt; 0.05). Relative to Sham group, SAH group exhibited decreased diameter and area of the basilar artery, reduced neuronal density, increased neuronal apoptosis rate, decreased levels of SOD, GSH-Px, and NO in the CSF, and increased levels of MDA and ET-1 (P &lt; 0.05). Moreover, LevoBPV Hcl group and LevoBPV Hcl/PLGA group showed increased diameter and area of the basilar artery, higher neuronal density, reduced neuronal apoptosis rate, elevated levels of SOD, GSH-Px, and NO in the CSF, and decreased levels of MDA and ET-1 versus SAH group (P &lt; 0.05). The LevoBPV Hcl/PLGA group exhibited increased diameter and area of the basilar artery, higher neuronal density, reduced neuronal apoptosis rate, elevated levels of SOD, GSH-Px, and NO in the CSF, and decreased levels of MDA and ET-1 versus LevoBPV Hcl group (P &lt; 0.05). In short, LevoBPV HCl-loaded nanospheres can prolong the in vivo residence time of subcutaneous and subarachnoid administration, reduce the maximum blood drug concentration, and enhance drug safety. Furthermore, these nanospheres can inhibit neuronal apoptosis following SAH, regulate oxidative stress and vasoconstrictor factor expression, thereby suppressing the occurrence of delayed cerebral vasospasm and alleviating brain tissue damage.

Sexual dimorphism in physiological responses of turbot (Scophthalmus maximus L) under acute hypoxia and reoxygenation

Dissolved oxygen (DO) is a crucial factor throughout fish life cycle. In this study, the hematology, hepatic antioxidant levels, histomorphology of the liver and gill were determined in both female and male turbot under acute hypoxia to evaluated the underlying mechanisms and potential sexual dimorphism difference. Results showed that acute hypoxia stress treatment for 3 h significantly increased plasma cortisol, glucose, hemoglobin (HGB), cholesterol (CHO), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and hepatic malondialdehyde (MDA) contents, red blood cell count (RBC) number, hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) activity in both male and female turbot. Male obtained higher plasma CHO, TG and LDL contents, GSH-Px and SOD activity than female under hypoxia. Meanwhile, hypoxia increased gill respiratory frequency, secondary lamellar length, secondary lamellar width, perimeter, lamellar surface area and gill surface area and decreased interlamellar distance. Acute hypoxia induced clubbing, hyperplasia, hypertrophy of gill filaments and hepatic vacuolization in both male and female turbot. The aforementioned parameters were recovered to normal levels after reoxygenation for 12 h. In conclusion, sex dimorphism difference of turbot hematological (RBC, HGB) and biochemical (glucose, CAT, GSH-Px, MDA) parameters were observed under hypoxia stress, while male demonstrated more hypoxia tolerance than female. These results help understand turbot hypoxia tolerance mechanisms and provide more data for management in captivity.

Protective effect of Ficus capensis lyophilized extract against carboplatin-induced liver injury via inhibition of oxidative stress and inflammation in rats

Patients who are receiving carboplatin therapy for cancer often experience toxic side effects. This study examined the effects of lyophilized aqueous leaf extracts of F. capensis (LALEFC) on oxidative stress and inflammatory markers in albino rats with carboplatin-damaged livers. We randomly assigned 35 rats to five experimental groups. Groups 2–5 underwent liver injury induction using carboplatin, while groups 1 and 2 served as the normal and carboplatin control groups, respectively. Groups 3-5 were the treatment groups. Treatments were performed for 17 days. We analyzed the quantitative phytochemical constituents of LALEFC using standard procedures and analyzed the liver oxidative stress and inflammatory markers using liver homogenate. The phytochemical constituents of LALEFC (mg/100g) occur in the following order: The most abundant compounds were phenols (1577.72 ± 0.008), flavonoids (1253.13 ± 0.007), tannins (878.97 ± 0.007), alkaloids (652.66 ± 0.007), glycosides (314.39 ± 0.011), and terpenoids (261.18 ± 0.154), while steroids (0.573 ± 0.062), saponins (0.370 ± 0.003), and HCN (0.254.00 ± 0.006) were found in trace amount. The study of oxidative stress and inflammatory markers showed that giving carboplatin to rats greatly increased the levels of interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-α), malondialdehyde (MDA), reactive oxygen species (ROS), and caspase-3 activity. It also decreased the levels of reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). D). However, coadministration of LALEFC significantly restored the altered oxidative and inflammatory responses. This finding suggested that carboplatin induced liver injury through redox imbalance, which elevated the expression of inflammatory markers. LALEFC's restoration of altered markers could be relevant in the treatment of carboplatin-induced liver injury.

Deltamethrin increased susceptibility to Aeromonas hydrophila in crucian carp through compromising gill barrier

Pyrethroids serve as a significant method for managing and preventing parasitic diseases in fish. Among these, deltamethrin (DEL) is used extensively in aquatic environments. Our previous work has been confirmed that DEL exposure can induce oxidative stress and immunosuppression on the gill mucosal barrier of crucian carp (Carassius auratus). However, it is not clear whether DEL affects the susceptibility of farmed fish to bacterial infection. In this study, fish was pre-exposed to different DEL concentration (0, 0.3 and 0.6 μg L−1) and then challenged by immersion with Aeromonas hydrophila (1.0 × 10ˆ8 CFU mL−1). After immersion challenge, fish pre-exposed to DEL developed prominent lipopolysaccharides level in gill and serum and had a significantly lower survival rate compared to the control group. In DEL pre-exposure fish after immersion, the gill apoptosis levels were significantly higher and disrupted the tight junction barrier by downregulating the zo1 and claudin12. Furthermore, fish pre-exposed to DEL exhibited increased activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and malonaldehyde (MDA) levels in the early stage after immersion but experiencing decreased activities of glutathione peroxidase (GPx) and lysozyme (LZM) in the later stage after immersion. And this process was regulated by the NRF2 pathway. Additionally, fish pre-exposed to DEL after immersion had significantly lower mRNA levels of immune-related genes tlr4, myd88, tnfα, and il-1β. Overall, these findings indicate that DEL damaged the gill barrier, weakened the immune response, raised LPS levels, and heightened vulnerability to A. hydrophila infection in crucian carp, resulting in mortality. Thus, this work will help social groups and aquaculture workers to understand the potential risk of DEL exposure for bacterial secondary infection in cultured fish.

Effects of dietary propyl gallate and Lactobacillus plantarum addition on growth, intestinal morphology, antioxidant capacity, and immune functions of Pekin ducks

The interaction between probiotic bacteria and polyphenol antioxidants can potentially enhance animal health. The present study examined the effects of propyl gallate and Lactobacillus plantarum supplementation on the growth, intestinal morphology, antioxidant capacity, and immune functions of Pekin ducks. A total of 128 male Pekin ducks (7-day-old) were allocated to 4 treatment groups with 4 replicates of 8 birds each. The ducks were fed the corn-soybean based diet (the control), supplemented with either propyl gallate (100 mg/kg), Lactobacillus plantarum (4×109 CFU/kg), or both, for 5 weeks. Dietary supplementation with propyl gallate and Lactobacillus plantarum had no significant effect on feed intake (P > 0.05), but increased average daily gain (P < 0.05). Lactobacillus plantarum also reduced the feed/gain ratio (P < 0.05). Villus height (VH) in the duodenum and ileum was increased by supplementation, while only propyl gallate supplement increased VH in the jejunum (P < 0.05). Supplementation had no effect on small intestine crypt depth (P > 0.05). Enhanced total superoxide dismutase activity was observed with supplementation (P < 0.05), but no effects were seen on catalase, malondialdehyde, total antioxidant capacity, and glutathione peroxidase values (P > 0.05). Serum immunoglobulin G was increased with Lactobacillus plantarum (P < 0.05), but not with propyl gallate (P > 0.05). No change in IgA and IgM concentrations was observed with supplementation. In conclusion, dietary supplementation with propyl gallate, Lactobacillus plantarum, or both, enhanced the villus height of the small intestines, improving the growth rate of Pekin ducks. The synergistic effects of both propyl gallate and Lactobacillus plantarum on the villus height and serum T-SOD activity surpassed the individual effects of each supplement in Pekin ducks.

Ablating the glutaredoxin-2 (Glrx2) gene protects male mice against non-alcoholic fatty liver disease (NAFLD) by limiting oxidative distress.

In the present study, we investigated the consequences of deleting the glutaredoxin-2 gene (Glrx2-/-) on the development of non-alcoholic fatty liver disease (NAFLD) in male and female C57BL6N mice fed a control (CD) or high-fat diet (HFD). We report that the HFD induced a significant increase in body mass in the wild-type (Wt) and Glrx2-/- male, but not female, mice, which was associated with the hypertrophying of the abdominal fat. Interestingly, while the Wt male mice fed the HFD developed NAFLD, the deletion of the Glrx2 gene mitigated vesicle formation, intrahepatic lipid accumulation, and fibrosis in the males. The protective effect associated with ablating the Glrx2 gene in male mice was due to enhancement of mitochondrial redox buffering capacity. Specifically, liver mitochondria from male Glrx2-/- fed a CD or HFD produced significantly less hydrogen peroxide (mtH2O2), had lower malondialdehyde levels, greater activities for glutathione peroxidase and thioredoxin reductase, and less protein glutathione mixed disulfides (PSSG) when compared to the Wt male mice fed the HFD. These effects correlated with the S-glutathionylation of α-ketoglutarate dehydrogenase (KGDH), a potent mtH2O2 source and key redox sensor in hepatic mitochondria. In comparison to the male mice, both Wt and Glrx2-/- female mice displayed almost complete resistance to HFD-induced body mass increases and the development of NAFLD, which was attributed to the superior redox buffering capacity of the liver mitochondria. Together, our findings show that modulation of mitochondrial S-glutathionylation signaling through Glrx2 augments resistance of male mice towards the development of NAFLD through preservation of mitochondrial redox buffering capacity. Additionally, our findings demonstrate the sex dimorphisms associated with the manifestation of NAFLD is related to the superior redox buffering capacity and modulation of the S-glutathionylome in hepatic mitochondria from female mice.

Melatonin Alleviates High Glucose-induced Oxidative Stress and Mitochondrial Dysfunction in Chondrocytes

Background: Hyperglycemia triggers mitochondrial dysfunction in chondrocytes, potentially contributing to cell damage and the onset of osteoarthritis. Objective: This study is undertaken with the objective of examining the protective properties of melatonin against toxicity induced by high glucose in C28I2 human chondrocytes. Methods: To determine non-cytotoxic concentrations of melatonin, various concentrations (10, 25, 50, 75, 100, 500, and 1000 μM) were assessed over different time periods (24, 48, and 72 hours) for their impact on C28I2 cell viability. Following this, cells underwent a pretreatment with melatonin (10 and 100 μM) for 6 hours. This was followed by subjecting the cells to a high concentration of glucose (75 mM) for 48 hours. Oxidative stress markers, including reactive oxygen species (ROS) and malondialdehyde (MDA), alongside the enzymatic activities of glutathione peroxidase, superoxide dismutase, and catalase were quantitatively assessed. To assess mitochondrial function, we evaluated the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio and measured the mitochondrial membrane potential (MMP). Results: Elevated glucose levels significantly increased ROS and MDA levels, accompanied by reduced MMP, an elevated ADP/ATP ratio, and altered antioxidant enzyme activity. Pretreatment with melatonin effectively reversed the mitochondrial toxicity induced by high glucose (75 mM). Conclusion: These results indicate that melatonin exhibits a protective influence against hyperglycemia- induced toxicity in chondrocyte mitochondria.

Combinatorial accumulation, stress response, detoxification and synaptic transmission effects of cadmium and selenium in clams Ruditapes philippinarum

This study investigated the toxicological effects and mechanisms of cadmium (Cd) (5 and 50 μg/L) and selenium (Se) (3 and 30 μg/L) at environmentally relevant concentrations on the gills and digestive glands of clams Ruditapes philippinarum. Results indicated that Cd and Se could tissue-specifically impact osmoregulation, energy metabolism, and synaptic transmission in the gills and digestive glands of clams. After exposure to 50 μg/L Cd, the digestive glands of clams up-regulated the expression of methionine-gamma-lyase and metallothionein for detoxification. Clam digestive glands exposed to 3 μg/L Se up-regulated the expression of catalase and glutathione peroxidase to alleviate oxidative stress, and down-regulated the expression of selenide-water dikinase to reduce the conversion of inorganic Se. Additionally, the interaction mode between Cd and Se largely depended on their molar ratio, with a ratio of 11.71 (50 μg/L Cd + 3 μg/L Se) demonstrated to be particularly harmful, as manifested by significantly more lesions, oxidative stress, and detoxification demand in clams than those exposed to Cd or Se alone. Collectively, this study revealed the complex interaction patterns and mechanisms of Cd and Se on clams, providing a reference for exploring their single and combined toxicity.

LncRNA HOXA11-AS intercepts the POU2F2-mediated downregulation of SLC3A2 in osteoarthritis to suppress ferroptosis

BackgroundOsteoarthritis (OA) is a prevalent ailment characterized by the gradual degradation of joints, resulting in discomfort and restricted movement. The recently proposed mechanism of ferroptosis is intricately associated with the initiation and progression of OA. Our study found that the long non-coding RNA HOXA11-AS reduces ferroptosis by increasing the expression of SLC3A2 through the transcription factor POU2F2. Materials and methodsHOXA11-AS was identified through lncRNA microarray analysis, and its impact on chondrocytes and extracellular matrix was assessed using real-time quantitative PCR, western blotting, and CCK8 assays. Subsequently, overexpression of HOXA11-AS in the knee joints of mice confirmed its protective efficacy on chondrocyte phenotype in the OA model. The involvement of HOXA11-AS in regulating ferroptosis via SLC3A2 was further validated through RNA sequencing analysis of mouse cartilage and the assessment of malondialdehyde levels and glutathione peroxidase activity. Finally, a combination of RNA sequencing, pull-down assays, mass spectrometry (MS), and chromatin immunoprecipitation (ChIP) techniques was employed to identify POU2F2 as the crucial transcription factor responsible for repressing the expression of SLC3A2, which can be effectively inhibited by HOXA11-AS. ResultsOur study demonstrated that HOXA11-AS effectively enhanced the metabolic homeostasis of chondrocytes, and alleviated the progression of OA in vitro and in vivo experiments. Furthermore, HOXA11-AS was found to enhance SLC3A2 expression, a key regulator of ferroptosis, by interacting with the transcriptional repressor POU2F2. ConclusionsHOXA11-AS promotes SLC3A2 expression and inhibits chondrocyte ferroptosis, by binding to the transcriptional repressor POU2F2, offering a promising and innovative therapeutic approach for OA.

Neuroinflammation and oxidative redox imbalance drive memory dysfunction in adolescent rats prenatally exposed to Datura Stramonium

Although there have been reports indicating that Datura Stramonium (D. stramonium) may induce anticholinergic and neuropsychiatry effects, the compound is still being used for recreational and medicinal purposes while ingestion during pregnancy has been documented. Intriguingly, minimal studies have investigated the potential neurotoxic impact of D. stramonium exposure at various stages of gestation, including its potential implication on neurophysiological well-being later in life. The present study, therefore, examined spontaneous working memory and the expression of specific neurochemicals modulating crucial neural processes in adolescent rats exposed to high and low D. stramonium doses during different stages of gestation. Pregnant rats were orally infused with 150- or 500- mg/kg/day of D. stramonium either during mid- (second week; days 8–14) or late- (third week; days 15–21) gestation, while control rats received PBS at dosing periods. Behavioral characterization of offspring between postnatal days (PD) 40 and 41 in the Y-maze revealed that D. stramonium perturbed spatial working memory in rats, although locomotor activity was generally unaltered. In addition to SOD and nitric oxide downregulation, induction of oxidative stress in the hippocampus and prefrontal cortex (PFC) of young adult rats prenatally exposed to D. stramonium was corroborated by depletion of key antioxidant regulatory elements glutathione peroxidase, glutathione reductase and catalase, which was accompanied by lipid peroxidation shown by increased MDA levels. Whereas increased expression of acetylcholinesterase and LDH was seen in adolescent rats prenatally infused D. stramonium, acetylcholine levels were downregulated in both hippocampal and PFC lysates, suggesting cholinergic and metabolic dysfunctions. Immunohistochemical labelling of GFAP and IBA-1 revealed increased expression of reactive astrocytes and microglia respectively, while the accompanying TNFα upregulation in both the hippocampus (dentate gyrus) and PFC causally linked intrauterine D. stramonium exposure with neuroinflammatory responses postnatally. Overall, our data correlated postnatal spatial working memory dysfunction evoked by D. stramonium exposure during critical stages of embryonic development to oxidative redox impairment, cholinergic disruption and neuroinflammatory perturbations in rats.

Growth performance, fatty acid profile, antioxidant capacity, liver and gut histopathology in Asian seabass (Lates calcarifer) fed various levels of oxidized fish oil and vitamin E

A 60-day research was carried out to investigate interactive effects of dietary oxidized fish oil (OXFO) and vitamin E (Vit E) interaction effects on the growth, body composition and health indices in Asian seabass juveniles (Lates calcarifer, 21.9 ± 0.1 g). Fresh fish oil (FFO) and two levels of OXFO (50 and 100 % dietary inclusion level) along with three levels of Vit E (125, 250 and 500 mg) were used to design a 3 × 3 factorial research trial. Accordingly, nine experimental diets were formulated, including FFO+125 (FFO + 125 mg Vit E), FFO+250 (FFO + 250 mg Vit E), FFO+500 (FFO + 500 mg Vit E), 50 %OXFO+125 (blends (1:1) of FFO + OXFO +125 mg Vit E), 50 %OXFO+250 (blends (1:1) of FFO + OXFO +250 mg Vit E), 50 %OXFO+500 (blends (1:1) of FFO + OXFO +500 mg Vit E), 100 %OXFO+125 (OXFO +125 mg Vit E), 100 %OXFO+250 (OXFO +250 mg Vit E) and 100 %OXFO+500 (OXFO +500 mg Vit E). Four hundred five L. calcarifer juveniles were stocked into twenty-seven 300-L circular tanks (15 fish/tank), in a flow through system. The greatest and least final weights were recorded in fish fed 50 %OXFO+250 and 100 %OXFO+125 diets (129.4 vs. 114.8 g final weight) diets, respectively. Whole body lipid content in fish fed FFO+125 increased compared to the other treatments. Fish oil oxidation significantly reduced Vit E concentration in the liver, meanwhile supplementing diet with 500 mg Vit E enhanced Vit E contents of the liver and muscle (P < 0.05). Eicosapentaenoic acid and long chain polyunsaturated fatty acids (LC-PUFA) contents of fillet increased with increasing dietary OXFO content to 50 %, and supplementing diet with 250 mg Vit E enhanced LC-PUFA content of fillet. Hepatic catalase, superoxide dismutase and glutathione peroxidase activities reduced by supplementing diets with Vit E. Sever pathological alterations occurred in liver and gut of L. calcarifer by dietary inclusion of OXFO or high Vit E concentration (500 mg). In summary, supplementing OXFO containing diets with moderate levels of Vit E (250 mg) could improve growth performance and feed utilization by ameliorating oxidative stress indices, improving antioxidant capacity, and increasing body LC-PUFA content in L. calcarifer.