GPx Activity Research Articles

Chlorogenic Acid Plays an Important Role in Improving the Growth and Antioxidant Status and Weakening the Inflammatory Response of Largemouth Bass (Micropterus salmoides).

This experiment evaluated the function of chlorogenic acid (CGA) in the growth, health status, and inflammation of largemouth bass (Micropterus salmoides). Over eight weeks, CGA supplementation was designed at five levels: 0, 60, 120, 180, and 240 mg/kg. The 180 and 240 mg/kg CGA-supplemented groups showed significant improvements in the FBW, SGR, and WGR compared to the control group (0 mg/kg) (p < 0.05). All the CGA-supplemented groups exhibited a significant reduction in the FCR (p < 0.05), with the 180 mg/kg CGA group showing the lowest FCR. Nonetheless, there were no appreciable differences in the plasma concentrations of TP, ALT, or AST among the treatments (p > 0.05). Compared to the control group, the 180 mg/kg CGA group exhibited significantly lower TC and TG levels (p < 0.05). The ALP levels showed no significant differences from the control group (p > 0.05). In terms of antioxidant parameters, CGA supplementation considerably reduced the MDA content (p < 0.05) and increased the GSH levels, while decreasing the CAT, SOD, and GPx activity levels Meanwhile, CGA supplementation resulted in reduced mRNA levels of SOD, CAT, Nrf2, Keap1, and NF-κB compared to the control group. In contrast, the mRNA levels of GPx, IL-8, TLR2, and RelA were elevated in the liver. Our findings indicated that CGA supplementation improved the growth performance and antioxidant status and weakened the inflammatory response of largemouth bass. These findings suggest that CGA could be a valuable dietary supplement for enhancing the health and growth of this species.

Potential benefits of advanced chelate-based trace minerals in improving bone mineralization, antioxidant status, immunity, and gene expression modulation in heat-stressed broilers.

Organic sources of trace minerals (TM) in broiler diets are more bioavailable and stable than inorganic sources, making them particularly beneficial during challenging periods such as heat stress (HS) conditions. A 42-d study investigated the effects of using advanced chelate technology-based TM (ACTM) or adding varying amounts of ACTM to broiler diets during HS conditions. The study involved 672 male broiler chickens in 7 treatment groups, including a thermoneutral control (TNC) group and six HS treatments. There were 8 replicate pens per treatment and 12 birds per replicate. The six HS treatments included birds exposed to a cyclic HS environment (34°C) for 8 h and were as follows: HSC, which consisted of the same basal diet with the recommended ITM levels; ACTM50 and ACTM100, which replaced the basal diet with 50% and 100% ACTM instead of ITM; ITM+ACTM12.5 and ITM+ACTM25, which involved adding extra ACTM to the ITM basal diet at 12.5% and 25%, respectively; and ITM125, which used 125% of the recommended levels of ITM in the basal diet. Compared with the HSC treatment, the TNC, ACTM100, and ITM+ACTM25 treatments resulted in increased (P < 0.05) body weight; tibia weight; tibia ash, phosphorus, iron, and manganese contents; secondary antibody titers; and serum TAC and SOD values but decreased (P < 0.05) serum MDA concentrations and the expression levels of the hepatic genes IL-1β, IL-6, and INF-γ. The TNC and ACTM100 groups also showed greater (P < 0.05) feed efficiency, tibia length, tibia zinc content, and hepatic SOD1 expression but exhibited reduced (P < 0.05) hepatic NF-kB expression. Significant increases (P < 0.05) in primary anti-NDV titers, serum GPx1 activity, and Nrf2 and GPx1 gene expression levels were also detected in the ACTM100, ITM+ACTM12.5, and ITM+ACTM25 groups. In conclusion, the findings suggest that replacing ITM with ACTM or adding ACTM to ITM diets, especially at a 25% higher dose, can effectively protect broilers from heat stress by promoting growth, reducing inflammation, and increasing the expression of antioxidant proteins.

Reno-protective potential of poncirin against polyethylene microplastics instigated kidney damage in rats via regulating Nrf-2/Keap-1 pathway

Polyethylene microplastics (PEMPs) are noxious environmental pollutants that are documented to cause organ damage including the kidneys. Poncirin (PON) is a naturally occurring flavonoid which demonstrates a wide range of pharmacological properties. This experiment was conducted to evaluate the palliative potential of PON against PEMPs by examining a range of biochemical and physiological parameters. Twenty-four male albino rats were randomly apportioned into four distinct groups including the control, PEMPs (1.5 mgkg−1), PEMPs (1.5 mgkg−1) + PON (20 mgkg−1) & only PON (20 mgkg−1). Our results displayed that PEMPs intoxication escalated the levels of urea, KIM-1, creatinine & NGAL while demising the creatinine clearance level. Besides reduction in the activities of GPx, GST, HO-1, CAT, GSR & upsurge in the levels of MDA and ROS were detected in PEMPs group. Conversely, the levels of inflammatory markers including COX-2, IL-1β, NF-kB and TNF-α were augmented following the PEMPs intoxication. Besides, the results of current research demonstrated that levels of Bax & caspase-3 were more than normal whereas the Bcl-2 expression was lowered from its standard value due to PEMPs provision. However, PON treatment significantly restored the PEMPs-induced biochemical impairments. Therefore, PON could be used as a therapeutic compound to ameliorate PEMPs-induced kidney impairments in rats, possibly due to its tremendous pharmacotherapeutic potential.

Synthesis, characterization and MAFLD prevention potential of Ganoderma lucidum spore polysaccharide-stabilized selenium nanoparticles

The unstability of selenium nanoparticles (SeNPs) results in decreased activity which limits its therapeutic potential. In this study, we utilized Ganoderma lucidum spore polysaccharide (GLP, Mw = 983.96 kDa) as a novel stabilizer to synthesize GLP-SeNPs. GLP-SeNPs (Se/GLP = 1/3) with an average diameter of 149 nm were successfully prepared and it was stable for at least 30 days at 4 °C. It exhibited an orange-red color, zero valence state, amorphous structure, selenium uniform distribution, a zeta potential of −29.73 mV, selenium content of 16.04 %. GLP-SeNPs pretreatment decreased lipid accumulation, reduced ROS content and enhanced SOD and CAT activity in HepG2 cells. Fe2+ and MDA contents were decreased, while GPX4 and GSH activities were increased. All these ameliorated effects could be abolished by NRF2 antagonist ML385. The expression of anti-oxidant genes and iron exporter was up-regulated, while that of pro-oxidant and lipid biosynthesis gene was down-regulated. The GPX4 activity could be reduced by ML385 addition. In conclusion, GLP-SeNPs was successfully constructed at the ratio of 1/3 (Se/GLP). It prevents MAFLD by targeting ferroptosis, including lowering iron overload, inhibiting lipid accumulation and attenuating oxidative stress. The improvement was conducted via activating SLC40A1-mediated iron pathway, ACSL4-mediated lipid metabolism and NRF2-mediated GSH-GPX4 pathway. Therefore, GLP-SeNPs can be used as potential selenium nutritional supplements or adjuvants for MAFLD prevention.

The Growth Inhibitory Effect of Resveratrol and Gallic Acid on Prostate Cancer Cell Lines through the Alteration of Oxidative Stress Balance: The Interplay between Nrf2, HO-1, and BACH1 Genes.

The association between oxidative stress and prostate cancer (PC) has been demonstrated both epidemiologically and experimentally. Balance in reactive oxygen species (ROS) levels depends on multiple factors, such as the expression of Nrf2, HO-1, and BACH1 genes. Natural polyphenols, such as resveratrol (RSV) and gallic acid (GA), affect cellular oxidative profiles. The present study investigated the possible effects of GA and RSV on the oxidative profiles of PC3 and DU145 cells, as well as Nrf2, HO-1, and BACH1 gene expression to achieve an understanding of the mechanisms involved. PC3 and DU145 cells were treated with ascending concentrations of RSV and GA for 72 h. Then cell growth and mRNA expression of Nrf2, HO-1, and BACH1 genes were analyzed by real-time PCR. Various spectrophotometric analyses were performed to measure oxidative stress markers. RSV and GA significantly decreased the growth of PC3 and DU145 cells compared to the control group in a concentration-dependent manner. RSV and GA also decreased ROS production in PC3 cells, but in DU145 cells, only the latter polyphenol significantly decreased ROS content. In addition, RSV and GA had ameliorating effects on SOD, GR, GPX, and CAT activities and GSH levels in both cell lines. Also, RSV and GA induced HO- 1 and Nrf2 gene expression in both cell lines. BACH1 gene expression was induced by RSV only at lower concentrations, in contrast to GA in both cell lines. Our data suggest that RSV and GA can prevent the growth of prostate cancer cells by disrupting oxidative stress-related pathways, such as changes in Nrf2, HO-1, and BACH1 gene expression.

Pyometra alters uterine aquaporins related with lipopolysaccharide concentrations and antioxidant enzyme activities in bitches

Pyometra is a common life-threatening inflammatory disease with a complex etiopathogenesis that develops during the diestrus stage and can be observed in elderly intact bitches. The present study evaluated five aquaporin (AQP1, AQP2, AQP3, AQP5, and AQP9) transcript abundances and immunolocalization in the uterine tissue, and investigated their relationship with uterine tissue and blood lipopolysaccharide (LPS) concentration, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activity, and nitric oxide (NO) production in dogs suffering from pyometra. The study sampled 36 client-owned intact bitches from different breeds, of which 24 cases were diagnosed with pyometra. Twelve of these bitches in the diestrus stage that presented for elective ovariohysterectomy were used as the control group. Blood samples were collected into tubes without anticoagulant for serum progesterone, LPS concentration, and antioxidant activities at the time of diagnosis. Bacteriological and tissue samples from the uteri were collected after the ovariohysterectomy. The tissue samples were used to determine antioxidant activity, and hormone and toxin concentrations. Transcript abundance of uterine AQPs were determined by qPCR, and their presence and localization were determined by by immunohistochemistry. For all pyometra samples, the bacteria isolated from the uterine swabs were Escherichia coli. Compared to the control group, AQP1, AQP2, and AQP5 were downregulated more than 2-fold, whereas AQP9 was upregulated nearly 3-fold and AQP3 was upregulated more than 4-fold in the pyometra affected uteri (P<0.05). Uterine AQP1 was moderately negatively correlated with serum LPS concentration (r=-0.568, P<0.01) and tissue NO production (r=-0.407, P<0.05). AQP5 was positively correlated with serum SOD activity (r=0.485, P<0.05) and negatively correlated with serum LPS concentration (r=-0.512, P<0.05). AQP9 was negatively correlated with tissue SOD and serum GPx activity. This is the first study to identify AQP9 transcript abundance and immunolocalization in canine uterine tissue. Uterine AQP1, AQP2, AQP3, AQP5, and AQP9 transcript abundances were altered in spontaneously developed canine pyometra while AQP transcript abundance was negatively related to serum toxin concentration, NO production, and antioxidant enzyme activity. Further studies should be conducted to determine the role of altered abundances of AQPs transcripts in pyometra pathogenesis.

Synergistic Benefits of Dietary Silymarin and Selenium on Growth, Immune Functions, Antioxidants, and Gut/Liver Health of Thinlip Mullet (Liza ramada) Juveniles

Abstract This study investigates the synergistic impact of silymarin (SI) levels combined with inorganic selenium (sodium selenite: Se) on growth, feed utilization, biochemical parameters, antioxidants, innate immunity, intestinal and liver histology, and gene expression of thinlip mullet (Liza ramada) juveniles. The experimental design involved thinlip mullets initially weighing 3.5±0.13 g, distributed in a completely randomized design with 30 fish per hapa (0.5 × 0.5 × 1 m), and conducted in triplicate over 60 days. Seven experimental diets were employed, including a control (without SI and Se supplementation), a negative control (with only Se supplementation), and four treatments with varying levels of silymarin (250, 450, 650, 850 mg/kg) alongside selenium (0.5 mg/kg diet). The growth performance results highlighted significant enhancements in final body weight, weight gain, and specific growth rate, particularly in the SI 850 mg/kg + Se treatment. Survival rates, feed intake, and feed conversion ratios showed positive trends across the SI-Se supplemented groups. Biochemical profiles of serum exhibited that the control diet induced elevated concentrations of glucose, cholesterol, alanine aminotransferase, aspartate aminotransferase, and urea, while Se or SI supplementation significantly mitigated these levels, with the lowest concentrations observed in the SI-Se supplemented groups. Moreover, SI supplementation increased serum protein content. Antioxidant enzyme activities, represented by superoxide dismutase (SOD), catalase (CAT), and catalase (GPx), demonstrated notable improvements in the SI-Se fortified groups, with significantly elevated GPx activity compared to the Se-supplemented and control groups. Immune system responses, including lysozyme, bactericidal, nitro-blue tetrazolium (NBT%), and serum alternative complement pathway (ACH50) activities, were highest in the SI-Se augmented groups. SI and Se in L. ramada reduce liver pro-inflammatory gene expression (IL-1 β, hepcidin) vs. control group. Histological examinations of the intestine and liver depicted structural enhancements, especially at moderate and high levels of SI with Se supplementation. The results indicate improved intestinal villi morphology and hepatic architecture, supporting the positive influence of dietary treatments on the health of thinlip mullet juveniles. In conclusion, the combined supplementation of SI at 850 mg/kg diet and Se at 0.5 mg/kg diet positively influenced the growth, biochemical profiles, antioxidant status, immune responses, gene expression, and histological integrity of thinlip mullet juveniles, providing valuable insights for optimizing aquafeed formulations.

Effect of Synthetic Wastewater on Antioxidant Defence System in Dreissena polymorpha

The effects of the synthetic wastewater on antioxidant defence system in Dreissena polymorpha evaluated. For this purpose, SOD, CAT, GPX activities and TBARS and GSH levels in tissues were determined by using commercial kits. The activities of SOD and CAT were in sythtetic group were determined lower than the control group in D. polymorpha during 24 and 96 h (p

Interleukin 1β And Interleukin-6 and Some Oxidants in Patients With Stable Angina

ROS play an essential physiological roles in the cellular homoeostasis and cell signaling under normal circumstances. The overexpression of ROS was involved in the pathological events of several diseases, including cardiovascular, because they cause damage to many cell structures.This study aims to evaluate the levels of inflammatory biomarkers, [interleukin-6 (IL-6) and interleukin-1beta (IL-1β)] in stable angina patients and their relationship with oxidative stress. The current study is a case-control one performed on 88 patients with stable angina and 44 people as a control group attending the Nasiriyah Heart Center from August 2023 to March 2024. All cases were diagnosed by cardiologists and confirmed by laboratory investigations. Blood samples (10 ml) were collected from patients. Serum was isolated after centrifugation and stored at -20°C. Serum CK-MB, MYO and Trop I were determined by electro-chemiluminescence immunoassay. While, the ELISA was employed to assess the levels of human IL-6, human IL-1 β, SOD, (GSH-Px/ GPX), total cholesterol, triglycerides, LDL, VLDL and HDL, using the kits from Solarbio, China. The patients with stable angina didn’t show significant variation in the serum level of troponin I and CK-MB in comparison with control, while serum myoglobin level was significantly increased in patients with stable angina compared to control. Although the level of total cholesterol was insignificantly increased, but the levels of triglyceride (TG), VLDL-C and LDL-C were significantly increased, while the serum level of HDL-C was significantly declined in comparison with control. The serum levels IL-6 and IL-1β, in addition to activities of SOD and GPx were increased significantly in patients of angina compared to control. We could conclude that IL-1β, IL-6, SOD and GPx are increased in stable angina. Inflammatory events and oxidative stress could play an important roles in initiation of atherosclerosis and subsequent angina.

Thymoquinone Abrogates Acrylamide-Induced Cerebellar Toxicity via Modulation of Nuclear Factor Erythroid 2-Related Factor 2/Nuclear Factor Kappa B Signaling, Oxidative Neuroinflammation, and Neuroapoptosis in Rats.

Acrylamide (ACR) is an obligate human neurotoxicant ubiquitously produced and found in foods processed at high temperature. There is an increasing public health concern regarding its probable carcinogenic potential. Its prevailing toxicity mechanism is oxidative inflammation and apoptosis. Herein, we explored whether thymoquinone (TQ), a bioactive quinone in Nigella sativa seed, could mitigate ACR-induced cerebellar toxicity in rats. Our study design featured four rat groups: control, TQ (5 mg/kg bw), ACR (50 mg/kg bw), and TQ + ACR (5 mg/kg + 50 mg/kg). After 14 days of respective treatments, cerebellar homogenate was used to estimate acetylcholinesterase activity (AchE) activity, antioxidant enzymes (catalase [CAT], superoxide dismutase [SOD], and glutathione peroxidase [GPx]), malondialdehyde (MDA), inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-4, and IL-10), nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), caspase-3, and caspase-9. The level of DNA damage by fragmentation and histopathological lesions was also determined in the cerebellum. The rat exposure to ACR caused significant decreases in the cerebellar activities of AchE, CAT, SOD, and GPx, IL-4, IL-10, and expression of Nrf2, whereas the levels of MDA, IL-6, TNF-α, caspase-3, and caspase-9 were prominently increased compared with the control. ACR induced significant DNA fragments and cerebellar lesions when compared with the control. Contrarily, TQ treatment inhibited the depression of CAT, SOD, and GPx activities and reversed the MDA level and expression of Nrf2/NF-κB, cytokines, and caspases. These effects were confirmed by reduced DNA damage and cerebellar histopathological lesions in comparison with the ACR. TQ afforded neuroprotection via its antioxidant, anti-inflammatory, and antiapoptotic mechanisms in rats.

Neuroprotective effect of Lannea egregia Alkaloid-rich leaf extracts in streptozotocin-induced diabetic rats

BackgroundStudies suggest that medicinal plant extracts can help reduce the neuron degeneration associated with diabetes. In this study, the neuroprotective effect of the alkaloid-rich extract from the leaves of Lannea egregia was assessed in rats with diabetes induced by streptozotocin (STZ). MethodsLannea egregia alkaloid-rich analysis was carried out via a known procedure. The rats were randomly assigned into five treatment groups (n = 8): normal control, diabetic-induced rats (45 mg/kg STZ), and diabetic rats treated with low doses of Lannea egregia leaf alkaloid-rich extract (50 mg/kg b.w, LEL) and high (100 mg/kg b.w, LEH) (300 mg/kg and 150 mg/kg), and metformin (200 mg/kg). On 22nd day of the experiment, animals were sacrificed, and their blood and brains were collected for neuro-biomarker analysis. ResultsDiabetic-induced rats that received metformin, LEL and LEH exhibited considerably reduced levels of dopamine, serotonin, norepinephrine, NO, MDA, and AChE, BChE activities when compared to untreated diabetic animals. Additionally, rats with diabetes that received treatment with metformin, LEL and LEH displayed a noticeable increase in ENTPDase, Na/K ATPase, GST, CAT, GPx, and SOD activities when compared to the untreated diabetic rats. Histological examination revealed improved brain architecture in the treated groups in contrast to those in diabetic-induced rats. ConclusionThe alkaloid-rich extracts of Lannea egregia might be effective in normalizing brain damage caused by complications of diabetes mellitus.

Tadalafil pretreatment attenuates doxorubicin-induced hepatorenal toxicity by modulating oxidative stress and inflammation in Wistar rats

Doxorubicin (DOX) is a widely used anticancer agent, but its clinical application is limited by significant off-target hepatorenal toxicity. Tadalafil (TAD), a selective phosphodiesterase-5 inhibitor used mainly for erectile dysfunction and pulmonary arterial hypertension, has shown potential in reducing oxidative stress. This study investigated TAD's chemoprotective effects and underlying mechanisms in DOX-induced hepatorenal toxicity in rats over 12 days. Eight groups of six rats each were orally pretreated with sterile water, silymarin (SIL), or TAD one hour before receiving intraperitoneal injections of 2.5 mg/kg DOX. On the 13th day, the rats were humanely sacrificed under inhaled halothane anesthesia, and serum was collected for hepatic and renal function tests, while liver and kidney tissues were analyzed for antioxidant enzyme activity, pro-inflammatory cytokines assay, and histopathological evaluation. DOX successfully induced hepatorenal toxicity, evidenced by significant increases (p<0.001, p<0.0001) in serum K+, urea, and creatinine levels, along with decreases in HCO3-, TCa2+, and Cl-. Tissue analysis showed reduced SOD, CAT, GST, and GPx activities, with elevated MDA and GSH levels. TAD pretreatment significantly ameliorated these biochemical alterations (p<0.05, p<0.001, p<0.0001), suggesting its potential as an effective chemoprophylactic adjuvant in the development of DOX-induced hepatorenal toxicity.

Biochemical responses of crayfish exposed to imidacloprid: assessment of oxidative stress, osmoregulatory response and neurotoxicity

ABSTRACT Among the nicotinoid insecticides, imidacloprid (IMI) may affect non-target invertebrates like aquatic crustaceans by entering the aquatic environment through rainfall. Nevertheless, there are not sufficient studies on the toxicity mechanism of IMI in crayfish. Here, we investigated the effects of IMI on oxidative stress, osmoregulatory, and neurotoxicity biomarkers. The 96-hour lethal concentration value (96 h-LC50) of IMI was determined to be 0.932 mg AI L−1. Four concentrations of IMI (0.932, 0.466, 0.233 and 0.117 mg AI L−1) were applied to crayfish for 96 h. Na+/K+-ATPase, Mg2+-ATPase, Ca2+-ATPase, and total ATPase activities had almost significantly concentration-related inhibition in both gill and muscle tissues (p < 0.05). Compare with control in hepatopancreas, the activities of GST, SOD and GPx were increased, while the activities of AChE, CES and GR were decreased (p < 0.05). As non-enzymatic parameters, a statistically significant (p < 0.05) increase in MDA levels and a decrease in GSH levels were observed in the hepatopancreas compared to the control group, which was not related to the concentration. In conclusion, it can be said that the study's biomarkers are highly helpful and that commercially consumed crayfish are a significant non-target organism in the assessment of IMI toxicity.

210 Maternal dietary organic selenium improves selenium status in neonatal lambs compared with single maternal or neonatal injection of inorganic selenium

Abstract The objective of this study was to compare the efficiency of three industry standard practices for improving the selenium (Se) status in neonatal lambs. Pregnant Polypay ewes (n = 27) at around 40 d pre-partum were enrolled in the study. The ewes were fed with grass silage and grain and, at 40 d from expected lambing, randomly allocated to one of three groups: 1) a single injection of 25 g sodium selenate as BO-SE/kg body weight (BW) at 4 wk before expected parturition (Inj-E) and not injection in the lambs; 2) no injection of BO-SE in the ewe but injection of 4.38 mg sodium selenite as BO-SE at 3 d of life of the lambs (Inj-L); and 3) no injection of BO-SE to the ewes or lambs but the ewes were fed 3.6 mg Se/day as Se-yeast (Yst-E) through the duration of the study (40 d prepartum + 30 d postpartum). Lambs were nursed by their own dams for 30 d without access to other feed (i.e., only milk). Blood was collected from the lambs at d 3 and 10 of life to measure 14 minerals, including Se, using ICP-MS. Glutathione peroxidase activity (GPx) was measured using a commercial kit. Data were analyzed using a GLIMMIX of SAS with an ARH covariance with treatment and time as the main effect, with lambs nested in ewe as a random effect. The number of lambs/ewes was used as a covariate. The injection of BO-SE in the ewes did not affect concentrations of Se in the lambs at birth, as there were no differences in whole blood Se between lambs in Inj-E and lambs in Inj-L at 3 d of life (i.e., before Inj-L received the BO-SE). The injection of BO-SE did not affect the level of Se in the whole blood of lambs 7 d after the injection compared with baseline (i.e., 3 d of life). Consequently, there was no difference in whole blood Se between lambs in Inj-E and Inj-L groups (177 vs. 167 ng/mL, respectively). However, injection of Se in pre-parturient dams did improve GPx activity in offspring (P = 0.04). Lambs in Yst-E had significantly greater concentrations of Se in whole blood compared with the other two groups at both 3 and 10 d of life (281 ng/mL; P &amp;lt; 0.001). Our data demonstrate that the typical industry standard approach of injecting inorganic Se in prepartum ewes or neonatal lambs is ineffective while feeding Se-yeast to dams was effective in improving Se status in lambs.

Punica granatum L. peel extract protects diabetic nephropathy by activating the Nrf-2/HO-1 pathway.

Diabetes raises cardiovascular morbidity and mortality worldwide and causes retinopathy, neuropathy, and nephropathy. Punica granatum L. (Pomegranate) is a fruit that has been used for its medicinal properties in various cultures. This article aims to investigate the antioxidant, anti-inflammatory, anti-apoptotic activity of Punica granatum L. peel ethanol extract (PGE) and its efficacy on NF-κB and Nrf-2/HO-1 signaling pathways in kidney tissue of rats with streptozotocin-induced diabetes. Single dose STZ 60mg/kg/i.p. rats were given to induce diabetes and blood glucose measurements were taken 7 days later. PGE 10mg/kg/p.o. administered to the treatment groups for 20 days. Blood, kidney, and pancreas samples taken from anesthetized rats were analyzed biochemically and histopathologically. It was observed that STZ increased the levels of urea, uric acid and creatine in the blood, while PGE significantly decreased these parameters. The diabetic group had higher MDA and lower renal tissue GSH level, CAT, GPx, and SOD activity than the control group. STZ also enhanced inflammation, apoptosis, Bax, Caspase-3, and NF-κB expression, and decreased Bcl-2, HO-1, and Nrf-2 expression. Experimental results showed that PGE has the potential to alleviate the harmful effects on the kidney and pancreas by altering the mentioned parameters in diabetic rats.

A multibiomarker approach to assess the effects of a BPA analogue-contaminated diet in the crab Carcinus aestuarii

Bisphenol A analogues are largely used plasticisers that are going to replace bisphenol A in many sectors. Due to this replacement, their discharge and presence in the marine coastal areas are increasing, with unknown consequences for organisms and the trophic chain. This study assessed the effects of three different bisphenols (BPAF, BPF and BPS) - alone or as a mixture - provided via food (exposed clams) to the crab Carcinus aestuarii. First, clams were exposed for two weeks to 300 ng/L of each of the three bisphenols and their mixture (100 ng/L of each) to allow the bioaccumulation of the contaminants in bivalves. Then, crabs were fed for two weeks with BPA analogue-exposed clams, while unexposed clams were used to feed control crabs. After 7 and 14 days, haemolymph, gills and hepatopancreas were collected from crabs to measure a battery of biomarkers indicative of cytotoxicity, oxidative stress and damage, neurotoxicity, physiological performance (respiration and excretion rate) and electron transport system activity. Lastly, bioaccumulation of BPA analogues was assessed by UHPLC-HRMS in crabs. Our findings revealed that BPA analogue-exposed clams were able to alter total haemocyte count, haemocyte size and their proliferation. The activity of immune enzymes, such as phosphatases and phenoloxidase was altered. Moreover, we observed an impairment of antioxidant and detoxifying enzymes like SOD, CAT, GST and GPX activities. Alterations of metabolism-involved enzymes and physiological parameters and increased oxidative damage to macromolecules like proteins, lipids, and DNA were also observed in crabs. Among BPA analogues, only bioaccumulation of BPAF, which has the highest Logkow value among the tested bisphenols, was evidenced in crabs. Overall, the obtained results indicated that crabs, under the tested experimental conditions at least, underwent alterations in cellular, biochemical and physiological responses following a diet of bisphenol-exposed clams, suggesting a potential ecotoxicological risk in the marine food chain.

Antiapoptotic and antinociceptive effects of Achillea millefolium L. aqueous extract in rats with experimental painful diabetic neuropathy

Background and purpose: Neuropathy is one of the common complications of diabetes mellitus. This study aimed to determine the analgesic and antiapoptotic effects of the aqueous extract of Achillea millefolium L. (Ach) in rats with experimental painful diabetic neuropathy by behavioral and molecular procedures. Experimental approach: Thirty male Wistar rats were divided into 5 groups including control, diabetes + saline, and diabetes + Ach extract (doses of 150, 300, and 600 mg/kg/day for 3 weeks, orally). A tail-flick test was performed to assess the pain threshold in different groups. Western blotting test was used to evaluate the apoptotic (Bax, Bcl2, cleaved caspase-3, and cytochrome-c) and inflammatory (TNF-α and NF-kB) protein factors in the lumbar portion of the spinal cord tissue. Also, commercial assay kits were used to evaluate oxidative stress factors (MDA, GPx, and SOD enzyme activity) in the lumbar portion of the spinal cord tissue. Findings/Results: Results showed that administering Ach extract at the doses of 300 and 600 mg/kg/day significantly increased the nociception threshold in treated diabetic animals compared to untreated diabetic animals. Moreover, the treatment of diabetic animals with Ach extract (300 and 600 mg/kg/day) significantly reduced the oxidative stress, inflammation, and apoptosis biochemical indicators in the lumbar spinal cord tissue compared to the untreated diabetic group. Conclusion and implications: The findings showed that Ach extract has neuroprotective and anti-nociceptive effects in rats with diabetic neuropathy. The effects can be due to the inhibition of oxidative stress, inflammation, and apoptosis in the spinal cord tissue.

Bis-chalcones obtained via one-pot synthesis as the anti-neurodegenerative agents and their effect on the HT-22 cell line

In the area of research on neurodegenerative diseases, the current challenge is to search for appropriate research methods that would detect these diseases at the earliest possible stage, but also new active structures that would reduce the rate of the disease progression and minimize the intensity of their symptoms experienced by the patient. The chalcones are considered in the context of candidates for new drugs dedicated to the fight against neurodegenerative diseases. The synthesis of bis-chalcone derivatives (3a-3d), as aim molecules was performed. Their structures were established by applying 1H NMR, 13C NMR, MS, FT-IR and UV–Vis spectra. All bis-chalcones were synthesized from terephthalaldehyde and appropriate aromatic ketone as substrates in the Claisen-Schmidt condensation method and evaluated in the biological tests and in silico analysis. Compounds exerted antioxidant activity using the HORAC method (3a-3d) and decreased the activities of GPx, COX-2 (3b-3d), GR (3a-3c) and CAT (3a,3b). The high anti-neurodegenerative potential of all four bis-chalcones was observed by inhibition of acetyl- (AChE) and butyrylcholinesterase (BChE) and a positive effect on the mouse hippocampal neuronal HT-22 cell line (LDH release and PGC-1α, PPARγ and GAPDH protein expression). TD-DFT method (computing a number of descriptors associated with HOMO–LUMO electron transition: electronegativity, chemical hardness and potential, first ionization potential, electron affinity) was employed to study the spectroscopic properties. This method showed that the first excited state of compounds was consistent with their maximum absorption in the computed UV–Vis spectra, which showed good agreement with the experimental spectrum using PBE1PBE functional. Using in silico approach, interactions of bis-chalcones with selected targets (aryl hydrocarbon receptor (AhR) PAS-A Domain, ligand binding domain of human PPAR-γ, soman-aged human BChE-butyrylthiocholine complex, Torpedo californica AChE:N-piperidinopropyl-galanthamine complex and the COX-2-celecoxib complex) were characterized. Results obtained in in silico models were consistent with in vitro experiments.

Sensitivity of triple negative breast cancer cells to ATM-dependent ferroptosis induced by sodium selenite

Targeting ferroptosis, a type of cell death elicited by Fe2+ and lipid reactive oxygen species (L-ROS), provides a novel strategy for cancer therapy. Selenium has the potential to treat cancers by acting as a pro-oxidative agent, thus leading to cancer cell death. Here, we found that the triple negative breast cancer (TNBC) MDA-MB-231 cells were more sensitive to ferroptosis induced by sodium selenite (Na2SeO3) than that of non-TNBC MCF-7 cells. Na2SeO3 significantly elevated the level of L-ROS, MDA and Fe2+, decreased the content of GSH and the enzyme activity of GPx, disrupted the expression of ferroptosis related proteins such as GPx4 and FTH1, as well as compromised mitochondrial morphology in MDA-MB-231 cells. Moreover, ATM was activated by Na2SeO3 in MDA-MB-231 cells. Notably, Na2SeO3-induced ferroptosis was inhibited by ATM kinase inhibitor KU55933 or siATM, suggesting that Na2SeO3-induced ferroptosis was mediated by ATM protein in MDA-MB-231 cells. Our findings suggest a therapeutic strategy by ferroptosis against TNBC and deepened our understanding of ATM function.

Effect of Levetiracetam on Oxidant-Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats.

Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant-antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant-antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups' oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state.