Pb-induced Oxidative Stress Research Articles

Avicularin Attenuated Lead-Induced Ferroptosis, Neuroinflammation, and Memory Impairment in Mice.

Lead (Pb) is a common environmental neurotoxicant that results in abnormal neurobehavior and impaired memory. Avicularin (AVL), the main dietary flavonoid found in several plants and fruits, exhibits neuroprotective and hepatoprotective properties. In the present study, the effects of AVL on Pb-induced neurotoxicity were evaluated using ICR mice to investigate the molecular mechanisms behind its protective effects. Our study has demonstrated that AVL treatment significantly ameliorated memory impairment induced by lead (Pb). Furthermore, AVL mitigated Pb-triggered neuroinflammation, ferroptosis, and oxidative stress. The inhibition of Pb-induced oxidative stress in the brain by AVL was evidenced by the reduction in malondialdehyde (MDA) levels and the enhancement of glutathione (GSH) and glutathione peroxidase (GPx) activities. Additionally, in the context of lead-induced neurotoxicity, AVL mitigated ferroptosis by increasing the expression of GPX4 and reducing ferrous iron levels (Fe2+). AVL increased the activities of glycogenolysis rate-limiting enzymes HK, PK, and PYG. Additionally, AVL downregulated TNF-α and IL-1β expression while concurrently enhancing the activations of AMPK, Nrf2, HO-1, NQO1, PSD-95, SNAP-25, CaMKII, and CREB in the brains of mice. The findings from this study suggest that AVL mitigates the memory impairment induced by Pb, which is associated with the AMPK/Nrf2 pathway and ferroptosis.

Mitigating Pb-induced oxidative stress in rice plants by cerium oxide and iron oxide nanoparticles

Nanotechnology offers creative and effective solutions for addressing various environmental issues, such as heavy metals (HM). The rapidly increasing HM concentrations in agricultural land have drawn considerable attention. Nanoparticles (NPs) have special physiochemical features that help reduce stress. This study assessed the viability of applying CeO2NPs and FeONPs to rice plants at a concentration of 25 mg/L to effectively remove the detrimental effects of lead (Pb) by using various concentrations (100 and 200 ppm) on plant development and growth. To achieve the desired concentrations, a Pb solution was prepared by dissolving lead nitrate in distilled water and added to the soil. Interestingly, the application of CeO2NPs and FeONPs resulted in a notable increase in plant growth, biomass, gas exchange characteristics, antioxidant enzymatic activity (SOD, POD, APX, and CAT), their gene expressions, as well as other antioxidants (phenols, prolines, amino acids, flavonoids, anthocyanins, and ascorbic acids) while simultaneously reducing oxidative stress (MDA, H2O2, and electrolyte leakage) and Pb uptake in rice. Conversely, Pb elevation in the soil increased oxidative damage and organic acid exudation pattern in the rice. At 200 ppm, a significant rise in Pb content (416.67 % and 380 %) was found in the roots and leaves of rice plants. According to our findings, rice growth can be bio-stimulated by CeO2NPs and FeONPs. Subsequent investigations should focus on the persistent ecological consequences and molecular mechanisms associated with the application of cerium oxide and iron oxide nanoparticles in agriculture to reduce Pb-induced oxidative stress.

Se Alleviated Pb-Caused Neurotoxicity in Chickens: SPS2-GPx1-GSH-IL-2/IL-17-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury.

Lead (Pb), a heavy metal environmental pollutant, poses a threat to the health of humans and birds. Inflammation is one of the most common pathological phenomena in the case of illness and poisoning. However, the underlying mechanisms of inflammation remain unclear. The cerebellum and the thalamus are important parts of the nervous system. To date, there have been no reports of Pb inducing inflammation in animal cerebellums or thalami. Selenium (Se) can relieve Pb poisoning. Therefore, we aimed to explore the mechanism by which Se alleviates Pb toxicity to the cerebellums and thalami of chickens by establishing a chicken Pb or/and Se treatment model. Our results demonstrated that exposure to Pb caused inflammatory damage in cerebellums and thalami, evidenced by the characteristics of inflammation, the decrease in anti-inflammatory factors (interleukin (IL)-2 and interferon-γ (INF-γ)), and the increase in pro-inflammatory factors (IL-4, IL-6, IL-12β, IL-17, and nitric oxide (NO)). Moreover, we found that the IL-2/IL-17-NO pathway took part in Pb-caused inflammatory injury. The above findings were reversed by the supplementation of dietary Se, meaning that Se relieved inflammatory damage caused by Pb via the IL-2/IL-17-NO pathway. In addition, an up-regulated oxidative index malondialdehyde (MDA) and two down-regulated antioxidant indices (glutathione (GSH) and total antioxidant capacity (TAC)) were recorded after the chickens received Pb stimulation, indicating that excess Pb caused an oxidant/antioxidant imbalance and oxidative stress, and the oxidative stress mediated inflammatory damage via the GSH-IL-2 axis. Interestingly, exposure to Pb inhibited four glutathione peroxidase (GPx) family members (GPx1, GPx2, GPx3, and GPx4), three deiodinase (Dio) family members (Dio1, Dio2, and Dio3), and fifteen other selenoproteins (selenophosphate synthetase 2 (SPS2), selenoprotein (Sel)H, SelI, SelK, SelM, SelO, SelP1, SelPb, SelS, SelT, SelU, and selenoprotein (Sep)n1, Sepw1, Sepx1, and Sep15), suggesting that Pb reduced antioxidant capacity and resulted in oxidative stress involving the SPS2-GPx1-GSH pathway. Se supplementation, as expected, reversed the changes mentioned above, indicating that Se supplementation improved antioxidant capacity and mitigated oxidative stress in chickens. For the first time, we discovered that the SPS2-GPx1-GSH-IL-2/IL-17-NO pathway is involved in the complex inflammatory damage mechanism caused by Pb in chickens. In conclusion, this study demonstrated that Se relieved Pb-induced oxidative stress and inflammatory damage via the SPS2-GPx1-GSH-IL-2/IL-17-NO pathway in the chicken nervous system. This study offers novel insights into environmental pollutant-caused animal poisoning and provides a novel theoretical basis for the detoxification effect of Se against oxidative stress and inflammation caused by toxic pollutants.

Lignin intervention protected against Pb-induced oxidative stress and hypercholesterolemia via reducing Pb bioaccumulation and regulating gut microbiota in hamster

The widespread environmental heavy metal, Pb, is renowned for inducing irreversible damage to human health. Lignin, an original fiber, emerges as a promising natural candidate for mitigating lead toxicity owing to its exceptional adsorption capacity and biocompatibility. In this study, we conducted an investigation into the potential therapeutic effects of lignin derived from the bamboo (Dendrocalamus Latiforus) shoot shell (BSS-AAL) in alleviating Pb-induced oxidative stress and hypercholesterolemia in hamsters. Our findings demonstrated the remarkable ability of BSS-AAL to reduce Pb accumulation by 27–40% in plasma and 13–84% in tissues. Furthermore, BSS-AAL exerted reparative effects on the antioxidant system, evidenced by substantial reductions in plasma total cholesterol levels by at least 35% and hepatic cholesterol levels by an impressive 66%. Intervention with BSS-AAL also led to favorable alterations in the richness of key microbial genera, including norank_f__Erysipelotrichaceae, unclassified_f__Atopobiaceae, and norank_f__Eubacteriaceae, which are associated with modulating malonaldehyde accumulation, hepatic cholesterol 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, as well as short chain fatty acids synthesis. These findings substantiated BSS-AAL played a vital role in effectively modulating Pb-induced oxidative stress and hypercholesterolemia by reducing Pb accumulation and favorably influencing gut microbiota.

The Palliative and Antioxidant Effects of Hesperidin against Lead-Acetate-Induced Testicular Injury in Male Wistar Rats.

Lead (Pb)-induced reprotoxicity is a detrimental consequence of Pb exposure, which results in abnormal spermatogenesis, testicular degeneration, and pathogenic sperm changes. The association between impaired male reproductive function and Pb-induced oxidative stress (OS) has been demonstrated, with consequent testicular antioxidant deficiency. The current study investigated the protective role of the natural antioxidant hesperidin (HSD) against lead-acetate (PbAc)-induced testicular toxicity. Male Wistar rats (n = 40) were randomly divided into four experimental groups: Group I (negative control) received 2.0 mL/kg BW 0.9% saline; Group II received 100 mg/kg BW PbAc; Group III received 100 mg/kg BW HSD; and Group IV received HSD two hours before PbAc using the abovementioned doses. The treatments were administered daily for 30 consecutive days. The results showed that HSD treatment significantly restored PbAc-induced decrease in body, epididymal, and testicular weights as well as in semen parameters, reproductive hormones, and testicular markers of OS. Reduced MDA levels and improved testicular histopathological findings were also observed. Collectively, this study sheds light on the preventive role of HSD against PbAc-induced testicular injury, which is mediated via the suppression of OS and the modulation of reproductive hormones as well as the plausibility of HSD being used as a supplementary therapeutic option for recovery.

Molecular Mechanisms of Selenium Mitigating Lead Toxicity in Chickens via Mitochondrial Pathway: Selenoproteins, Oxidative Stress, HSPs, and Apoptosis.

Lead (Pb), a hazardous heavy metal, can damage the health of organisms. However, it is not clear whether Pb can damage chicken cerebellums and thalami. Selenium (Se), an essential nutrient for organisms, has a palliative effect on Pb poisoning in chickens. In our experiment, a model of chickens treated with Pb and Se alone and in combination was established to investigate the molecular mechanism of Se alleviating Pb-caused damage in both chicken cerebellums and thalami. Our morphological results indicated that Pb caused apoptotic lesions, such as mitochondrial and nuclear damage. Further, the anti-apoptotic gene Bcl-2 decreased; on the contrary, four pro-apoptotic genes (p53, Bax, Cyt c, and Caspase-3) increased under Pb treatment, meaning that Pb caused apoptosis via the p53-Cyt c-Caspase-3 pathway. Furthermore, we further demonstrated that Pb elevated four HSPs (HSP27, HSP40, HSP70, and HSP90), as well as HSP70 took part in the molecular mechanism of Pb-caused apoptosis. In addition, we found that Pb exposure led to oxidative stress via up-regulating the oxidant H2O2 and down-regulating four antioxidants (CAT, SOD, GST, and GPx). Moreover, Pb decreased three Se-containing factors (Txnrd1, Txnrd2, and Txnrd3), further confirming that Pb caused oxidative stress. Interestingly, Se supplementation reversed the above changes caused by Pb and alleviated Pb-induced oxidative stress and apoptosis. A time dependency was demonstrated for Bcl-2, Bax, and Cyt c in the cerebellums, as well as CAT, GPx, and p53 in the thalami of Pb-exposed chickens. HSP70 in cerebellums and HSP27 in thalami were more sensitive than those in thalami and cerebellums, respectively, under Pb exposure. Pb-induced apoptosis of thalami was more severe than cerebellums. In conclusion, after Pb treatment, Txnrds mediated oxidative stress, oxidative stress up-regulated HSPs, and finally, HSP70 triggered apoptosis. Se supplementation antagonized Pb-induced oxidative stress and apoptosis via the mitochondrial pathway and selenoproteins in chicken cerebellums and thalami. This study provides new information for the mechanism of environmental pollutant poisoning and the detoxification of Se on abiotic stress.

Unravelling blood-based epigenetic mechanisms: the impact of hsa-miR-146a and histone H3 acetylation in lead-induced inflammation among occupational workers.

Occupational and environmental exposure to lead (Pb) is a persistent health problem majorly in developing countries and has been implied to cause epigenetic alterations. Its effect on histone post-translational modifications is not explored in human population. MicroRNAs are epigenetic modulators reported to be differentially expressed under Pb exposure. The present study was targeted to find plausible association between the role of hsa-miR-146a and global histone (H3) acetylation in Pb-induced inflammation in occupationally exposed workers. A total of 100 occupationally exposed individuals working in different industries were recruited for the study and divided into 2 groups based on the median Pb levels [low Pb group (Pb < 5μg/dL) and High Pb group (Pb > 5μg/dL)]. The Pb levels were measured in whole blood using atomic absorption spectrometry to confirm Pb exposure. Histone H3 acetylation and serum interleukin-6 (IL-6) levels were measured using colorimetric methods and enzyme-linked immunosorbent assay (ELISA), respectively. MicroRNA-146a expression was quantified using TaqMan assay. The median BLL of the study population was 5μg/dL. BLL, IL-6, and Histone (H3) acetylation increased significantly with the duration of exposure. BLL level showed a significant positive correlation with IL-6 and histone H3 acetylation level. We also found that hsa-miR-146a exhibited significantly increased expression in the high Pb group compared to the low Pb group (Fold change: 2.56; P = 0.014). The linear regression model suggested that BLL has significantly predicted histone H3 acetylation, hsa-miR-146a, and IL-6 in the study subjects. The finding that hsa-miR146a was significantly upregulated in individuals with high BLL and had a significant negative correlation with serum IL-6 suggests that Pb-induced oxidative stress likely activates H3 acetylation, which then releases inflammatory cytokines like IL-6.

Pharmacological effect of Argyrolobium roseum (Camb.) Jaub & Spach extracts against lead-induced toxicity in rats.

Argyrolobium roseum (Camb.) Jaub & Spach (Papilionaceae) is a medicinal plant, cultivated in northern areas of Pakistan. The consumption of trace minerals (lead) is very toxic to the vital organs of the body, therefore the overcome of these minerals is very necessary. In this regard, this study aimed to assess the potential pharmacological effect of aqueous and ethanolic extract of Argyrolobium roseum (Camb.) Jaub & Spach against pb-induced oxidative stress, histological changes in Pb-induced rats' liver and kidney, and anti-inflammatory effect. The metal concentrations in liver and kidney homogenates were measured through atomic absorption spectrophotometer. The antioxidant activity was measured through DPPH and FRAP assay. Pb concentrations were significantly higher in liver and kidney homogenates after injection of Pb acetate was given intraperitoneally (45.2 ± 6.8 and 58.8 ± 7.9, respectively; p < .0001). The level of Pb in liver and kidney homogenates was significantly reduced by aqueous and ethanolic extracts of Argyrolobium roseum (Camb.) Jaub & Spach. The Pb + Aq-600 mg/kg-treated rats exhibited a protective effect on hepatocytes cells against Pb-induced liver injury and restored the cells of the kidney. Pb + Aq-600 mg/kg showed higher antioxidant activity as compared to other treated groups. The highest decreased MDA level was found in liver and kidney homogenate of Pb + Aq-600 mg/kg rats (11.2 ± 1.51 nmol/mg; p < .001) and GSH and CAT levels tended to normal after treatment of Pb + Aq-600 mg/kg in rats. The ALAD, ALT, AST, and ALP level were enhanced and tended to be normal after the Aq-400 and Aq-600 mg/kg treatment in Pb-exposed rats. The result showed that 600 mg/kg Aq + Pb exhibited significant (p < .001) anti-inflammatory activity. The findings of this study concluded that treatment of the aqueous extract of Argyrolobium roseum (Camb.) Jaub & Spach reduces the renal and hepatic damage in Pb-induced rats and it also decreases oxidative stress via improving antioxidant components.

Zinc Inhibits Lead-Induced Oxidative Stress and Apoptosis of ST Cells Through ROS/PTEN/PI3K/AKT Axis.

Lead (Pb) is a widely distributed toxic heavy metal element known to have strong male reproductive toxicity, which can result in issues such as abnormal count and morphology of sperm. Zinc (Zn) is an essential trace element for the human body that can antagonize the activity of Pb in some physiological environments, and it also possesses antioxidant and anti-inflammatory effects. However, the specific mechanism of Zn's antagonism against Pb remains largely unclear. In our study, we conducted research using swine testis cells (ST cells) and confirmed that the half maximal inhibitory concentration of Pb on ST cells was 994.4 μM, and the optimal antagonistic concentration of Zn was 10 μM. Based on this information, we treated ST cells with Pb and Zn and detected related indices such as apoptosis, oxidative stress, and the PTEN/PI3K/AKT pathway using flow cytometry, DCFH-DA staining, RT-PCR, and Western blot. Our results demonstrated that Pb exposure can generate excessive reactive oxygen species (ROS), disrupt the antioxidant system, upregulate PTEN expression, and inhibit the PI3K/AKT pathway in ST cells. In contrast, Zn significantly inhibited the overproduction of ROS, improved oxidative stress, and decreased PTEN expression, thus protecting the PI3K/AKT pathway compared to Pb-exposed ST cells. Furthermore, we found that Pb exposure exacerbated the expression of genes related to the apoptosis pathway and reduced the expression of anti-apoptotic genes. Furthermore, this situation was significantly improved when co-cultured with Pb and Zn. In summary, our study demonstrated that Zn alleviated Pb-induced oxidative stress and apoptosis through the ROS/PTEN/PI3K/AKT axis in ST cells.

Sildenafil attenuates oxidative stress and endothelial dysfunction in lead-induced hypertension.

Lead (Pb) reduces NO bioavailability, impairs the antioxidant system, and increases the generation of reactive oxygen species (ROS). Pb-induced oxidative stress may be responsible for the associated endothelial dysfunction. Sildenafil has shown nitric oxide (NO)-independent action, including antioxidant effects. Therefore, we examined the effects of sildenafil on oxidative stress, reductions of NO and endothelial dysfunction in Pb-induced hypertension. Wistar rats were distributed into three groups: Pb, Pb + sildenafil and Sham. Blood pressure and endothelium-dependent vascular function were recorded. We also examined biochemical determinants of lipid peroxidation and antioxidant function. ROS levels, NO metabolites and NO levels in human umbilical vein endothelial cells (HUVECs) were also evaluated. Sildenafil prevents impairment of endothelium-dependent NO-mediated vasodilation and attenuates Pb-induced hypertension, reduces ROS formation, enhances superoxide dismutase (SOD) activity and antioxidant capacity in plasma and increases NO metabolites in plasma and HUVECs culture supernatants, while no changes were found on measurement of NO released from HUVECs incubated with plasma of the Pb and Pb + sildenafil groups compared with the sham group. In conclusion, sildenafil protects against ROS-mediated inactivation of NO, thus preventing endothelial dysfunction and attenuating Pb-induced hypertension, possibly through antioxidant effects.

Identification and preparation of selenium-containing peptides from selenium-enriched Pleurotus eryngii and their protective effect on lead-induced oxidative damage in NCTC1469 hepatocytes.

Lead (Pb) is a highly toxic and persistent substance that easily accumulates in living organisms, eliciting cellular toxicity and oxidative stress. Some selenium-containing proteins and peptides prepared from plant extracts are beneficial for protecting the body's health and resisting external disturbances. In the present study, selenium-containing peptide species were prepared from selenium-enriched Pleurotus eryngii protein hydrolysates and to evaluate the benefits of selenium-containing peptides on Pb-induced oxidative stress in NCTC1469 hepatocytes. Trypsin was selected as primary enzyme to hydrolyze the selenium-enriched protein (SPH). The optimal hydrolysis conditions were: hydrolysis time, 1.5h; initial pH 8.0. The SPH was digested by trypsin and then purified by ultrafiltration, gel filtration chromatography and reversed-phase HPLC to obtain the selenium-containing peptides SPH-I-2. Furthermore, SPH-I-2 was analyzed and a number of total 12 selenium-containing peptides were identified by liquid chromatography-tandem mass spectroscopy. The NCTC1469 cell culture study showed that selenium-containing peptides were capable of reducing reactive oxygen species levels and regulating the Keap1/Nrf2 pathway by upregulating Nrf2, HO-1, GCLC, GCLM and NQO1 genes and downregulating Keap1 genes. Moreover, selenium-containing peptides were also able to suppress Pb-induced elevated levels of nitric oxide (NO), lactate dehydrogenase (LDH), malondialdehyde (MDA), increase antioxidant enzyme activity and alleviate cell apoptosis. The present study indicated that the selenium-containing peptides could protect cells from Pb2+ -induced oxidative stress. © 2023 Society of Chemical Industry.

Impacts of Pb-Induced Oxidative Stress on Morphological, Physiological and Biochemical Properties of Tree Species

Impacts of Pb-Induced Oxidative Stress on Morphological, Physiological and Biochemical Properties of Tree Species

Alleviating Effects of Black Soybean Peptide on Oxidative Stress Injury Induced by Lead in PC12 Cells via Keap1/Nrf2/TXNIP Signaling Pathway.

Many researchers have found that Pb exposure can cause oxidative stress damage to the body’s tissue. Black soybean peptide (BSP) has a variety of physiological functions, especially in terms of oxidative stress. Nevertheless, the mitigation function of BSPs on Pb-induced oxidative stress damage in PC12 cells has not been clearly defined. In this study, cell viability was detected by CCK8. Oxidative stress indicators, such as ROS, GSH/GSSG, MDA, SOD, CAT, GPx, and GR, were tested with biochemical kit. Protein expression of Keap1, Nrf2, and TXNIP was measured by Western blot. Compared with the control group, Pb reduced the cell viability of PC12 cells. However, BSP treatment significantly increased the viability of PC12 cells induced by lead exposure (p < 0.05). Lead can enrich the contents of MDA and ROS, but decrease the amount of CAT, SOD, GR, GPx, and GSH/GSSG in PC12 cells, while BSP can alleviate it (p < 0.05). Lead can enhance the expression of Keap1 and TXNIP proteins, but reduce Nrf2 expression. In contrast, BSPs reversed this phenomenon (p < 0.05). BSPs can alleviate oxidative stress injury induced by lead in PC12 cells through the Keap1/Nrf2/TXNIP signaling pathway.

Modulatory effects of dietary cinnamon (Cinnamomum zeylanicum) against waterborne lead toxicity in Nile tilapia fingerlings: Growth performance, haemato-biochemical, innate immunity, and hepatic antioxidant indices

This study investigated the protective effect of dietary cinnamon (Cinnamomum zeylanicum) powder (CzP) on the growth performance, haemato-biochemical, innate immunity, and hepatic antioxidant indices of tilapia (Oreochromis niloticus) fingerlings against the toxic effect of prolonged lead (Pb) exposure. Fish (22.6–25.3 g) were fed on diets supplied with two CzP levels (0.0 (control) and 10 g/kg diet) up to satiety for 60 days. At each CzP level, fish were exposed to 0.0 and 7.94 mg Pb/L in five replicates. At the end of this trial, Pb residues in the whole-fish body as well as haemato-biochemical, antioxidant, and immune indices were determined. The waterborne Pb adversely affected the growth performance, white blood cells and red blood cells counts, hematocrit, and hemoglobin levels. Blood cortisol, glucose, total cholesterol, serum alanine and aspartate aminotransferases and lactate dehydrogenase values were significantly higher; meanwhile, total lipids, total protein, albumin, and globulin as well as alkaline phosphatase were significantly lower in Pb-exposed fish. Hepatic oxidative stress biomarkers (malondialdehyde, superoxide dismutase, catalase, and total antioxidant activity) and serum immune indices (respiratory burst activity, serum lysozyme activity, and total immunoglobulins) were progressively suppressed by Pb exposure. On the other hand, the dietary supplementation of cinnamon powder alone significantly enhanced the growth, hemato-biochemical, antioxidant, and immune indices of Nile tilapia. Additionally, dietary CzP significantly mitigated Pb-induced effects in regard to the above-mentioned variables. Exposing Nile tilapia to Pb toxicity induced significant Pb accumulations in the whole-fish body; meanwhile the dietary CzP effectively reduced the Pb accumulation in the body of Pb-exposed fish. Thus, the dietary CzP had several encouraging effects on growth, antioxidant, and immune indices of Nile tilapia. Feeding the Pb-exposed fish with CzP effectively reduced the Pb accumulation in the fish body and offered direct protection against Pb-induced oxidative stress. The findings of the present study suggest that dietary cinnamon can be used as an immune-stimulant for mitigating the effects of heavy metals toxicity in Nile tilapia aquaculture.

Antagonistic effects of selenium on lead-induced oxidative stress and apoptosis of Leydig cells in sheep

The objective of this study was to investigate the antagonistic effects of selenium (Se) on lead (Pb)-induced oxidative stress and apoptosis of sheep Leydig cells and its underlying mechanism. Leydig cells collected from 8-month-old sheep were treated with Pb (40 μmol/L) and/or Se (2 μmol/L), respectively. CCK-8 assay was used to detect cell proliferation and apoptosis after cultured for 48 h. The abundances of pro-apoptosis (BAX, CASPASE 3 and CASPASE 8) and NRF2-related (NRF2, HO-1, NQO1 and γ-GCS) genes were detected by real-time PCR and western blot analysis, respectively.The results showed that the highest cell viability was observed in the Se group. Compared with the control group, Pb treatment led to the higher ROS level and greater abundances of BAX, CASPASE 3 and CASPASE 8 mRNA transcripts. Treatment with Pb + Se resulted in an increased (P < 0.05) abundances of NRF2, HO-1, NQO1 and γ-GCS mRNA transcripts and proteins. Compared with the Pb group, the Se + Pb treatment dramatically decreased (P < 0.05) the ROS level and relative abundances of pro-apoptosis genes. The greater (P < 0.05) abundances of pro-apoptosis and NRF2-related mRNA transcripts and proteins were also obtained in the Se + Pb group. The abundances of BAX, CASPASE 3 and CASPASE 8 genes in the SeML385 group were greater (P < 0.05) than in the Se group. Compared with the corresponding groups without ML385, treatment with ML385 decreased (P < 0.05) cell viability and the relative abundances of pro-apoptosis and NRF2-related genes.These results indicate that Pb-induced oxidative stress can inhibit the viability of Leydig cells by modulating pro-apoptosis gene expression. NRF2 pathway could be involved in the antagonistic effect of Se on Pb-induced apoptosis of Leydig cells in sheep. This study is expected to provide some experimental evidences for Se treatment of Pb-induced reproductive disorders.

Neuroprotective effects of Lippia javanica (Burm.F.) Spreng. Herbal tea infusion on Lead-induced oxidative brain damage in Wistar rats

BackgroundThough Lippia javanica (Burm.f.) Spreng antioxidant activity has been demonstrated, its effect in protecting the brain from lead (Pb)-induced oxidative damage is unknown. This study investigated the effect of L. javanica against Pb-induced oxidative stress, inflammation, apoptosis and acetylcholinesterase activity in rat’s brain.MethodsL. javanica herbal tea infusion was prepared, its phytochemical constituent was revealed by liquid chromatography-Mass spectrometer (LC-MS) and was administered simultaneously with Pb. Four groups of male Wistar rats (n = 5/group) were used: control received distilled water; Pb-acetate group received 50 mg Pb/ Kg bodyweight (bw), treatment group received 50 mg Pb/ Kg Pb-acetate + 5 ml/kg bw L. javanica and L. javanica group received 5 ml/Kg bw of L. javanica tea infusion only. After 6 weeks of treatment, oxidative status, acetylcholinesterase activity, inflammation and apoptosis was assessed in brain tissue which was also histologically examined.ResultsMean brain and heart weight was reduced (p < 0.05) while liver and spleen weights were increased (p < 0.05) in Pb exposed animals but were prevented by L. juvanica treatment. Treatment with L. javanica increased (p < 0.05) overall brain antioxidant status (glutathione and superoxide dismutase activities) and reduced lipid peroxidation (p < 0.05) compared to the Pb exposed animals. Pro-inflammatory cytokine tumour necrotic factor-alpha, pro-apoptosis Bax protein and anticholinesterase activity were reduced (p < 0.05) in Pb-L. javanica treated animals compared to the Pb exposed group. Histological examination confirmed neuroprotective effects of L. javanica as evidenced by reduced apoptosis/necrosis and inflammation-induced vacuolization and oedema in the hippocampus. The L. javanica treatment alone had no detrimental effects to the rats. LC-MS analysis revealed L. javanica to be rich in phenolics.ConclusionsThis study demonstrated that L. javanica, rich in phenolics was effective in reducing Pb-induced brain oxidative stress, inflammation, apoptosis, acetylcholinesterase activity and neuronal damage.

Dietary α-lipoic acid can alleviate the bioaccumulation, oxidative stress, cell apoptosis, and inflammation induced by lead (Pb) in Channa argus

This study aims to evaluate the effects of dietary α-lipoic acid (α-LA) on bioaccumulation, oxidative stress, apoptosis, and inflammation in Channa argus after 28 d of lead (Pb) exposure. A total of 300 fish were divided into five groups: the first group was the control group and the other four groups were exposed to waterborne Pb (800 ppb) and fed α-LA diets supplemented with 0, 300, 600, and 900 mg/kg. The results demonstrated that dietary α-LA effectively reduced the Pb accumulation in the liver, kidney, gill, intestine, and muscle of C. argus after exposure to Pb. Meanwhile, dietary α-LA reversed alterations in the biochemical parameters (Alanine aminotransferase (ALT), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), blood urea nitrogen (BUN), cortisol (COR), and creatinine (CRE)) and immunity parameters (myeloperoxidase (MPO), complement 3 (C3), lysozyme (LYS), complement 4 (C4), C-reactive protein (CRP), and immunoglobulin M (IgM)) in the serum of fish caused by Pb. Pb-induced reduction of antioxidant enzyme activities (Catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px)) was inhibited by dietary α-LA. And malondialdehyde (MDA) and protein carbonyl (PC) content exhibited an opposite trend. Meanwhile, dietary supplemented with α-LA was found to relieve Pb-induced oxidative stress by downregulating Keap1 mRNA expression levels and upregulating the expression levels of CAT, nuclear factor erythroid 2-related factor 2 (Nrf2), GSH-Px, and Cu/Zn SOD. Furthermore, α-LA supplementation reversed Pb-induced upregulation of pro-inflammatory genes (interleukin (IL)-6, IL-1β, tumor necrosis factor α (TNF-α), and nuclear factor kappa B (NF-κB)), Pro-apoptotic genes (Bcl-2-associated X (Bax), caspase (Cas)-3, and tumor protein p53 (p53)) and Hsp70, and downregulation of anti-inflammatory genes (IL-10, inhibitor of κBα (IκBα), and transforming growth factor β (TGF-β)) and anti-apoptosis gene (B-cell lymphoma-2 (Bcl-2)). Overall, dietary α-LA supplementation could enhance the innate immunity and antioxidant capacity of fish, attenuating the Pb accumulation, and cell apoptosis after being exposed to Pb. Furthermore, dietary α-LA could relieve Pb-induced inflammatory response and oxidative stress of fish via regulating NF-κB and Nrf2 signaling, respectively.

Lead (Pb)-induced oxidative stress mediates sex-specific autistic-like behaviour in Drosophila melanogaster.

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterised by three main behavioural symptoms: abnormal social interaction, verbal and non-verbal communication impairments, and repetitive and restricted activities or interests. Even though the exact aetiology of ASD remains unknown, studies have shown a link between genetics and environmental pollutants. Heavy metal lead (Pb), the environmental pollutant, is associated with ASD. Pb may also exhibit sex-specific ASD behaviour, as has been demonstrated in the global human populations. Drosophila melanogaster as a model has been used in the present study to understand the involvement of Pb-induced oxidative stress in developing ASD behaviour. The larval feeding technique has been employed to administer different Pb concentrations (0.2-0.8mM) to Oregon-R (ORR), superoxide dismutase (Sod), or catalase (Cat) antioxidants overexpressed or knockdown flies. Adult Drosophila (5-day old) were used for Pb content, biochemical, and behavioural analysis.Pb accumulated in the Drosophila brain induces oxidative stress and exhibited a human autistic-like behaviour such as reduced climbing, increased grooming, increased social spacing, and decreased learning and memory in a sex-specific manner.Pb-induced autistic-like behaviour was intensified in Sod or Cat-knockdown flies, whereas Sod or Cat-overexpressed flies overcome that behavioural alterations. These results unequivocally proved that Pb-induced oxidative stress causes ASD behaviour of humans in Drosophila. Thus, Drosophila is used as a model organism to analyse ASD-like human behaviour and underlines the importance of using antioxidant therapy in alleviating ASD symptoms in children.

Protective Effect of Chlorogenic Acid and Its Analogues on Lead-Induced Developmental Neurotoxicity Through Modulating Oxidative Stress and Autophagy.

Lead (Pb) is among the deleterious heavy metal and has caused global health concerns due to its tendency to cause a detrimental effect on the development of the central nervous system (CNS). Despite being a serious health concern, treatment of Pb poisoning is not yet available, reflecting the pressing need for compounds that can relieve Pb-induced toxicity, especially neurotoxicity. In the quest of exploring protective strategies against Pb-induced developmental neurotoxicity, compounds from natural resources have gained increased attention. Chlorogenic acid (CGA) and its analogues neochlorogenic acid (NCGA) and cryptochlorogenic acid (CCGA) are the important phenolic compounds widely distributed in plants. Herein, utilizing zebrafish as a model organism, we modeled Pb-induced developmental neurotoxicity and investigated the protective effect of CGA, NCGA, and CCGA co-treatment. In zebrafish, Pb exposure (1,000 μg/L) for 5 days causes developmental malformation, loss of dopaminergic (DA) neurons, and brain vasculature, as well as disrupted neuron differentiation in the CNS. Additionally, Pb-treated zebrafish exhibited abnormal locomotion. Notably, co-treatment with CGA (100 µM), NCGA (100 µM), and CCGA (50 µM) alleviated these developmental malformation and neurotoxicity induced by Pb. Further underlying mechanism investigation revealed that these dietary phenolic acid compounds may ameliorate Pb-induced oxidative stress and autophagy in zebrafish, therefore protecting against Pb-induced developmental neurotoxicity. In general, our study indicates that CGA, NCGA, and CCGA could be promising agents for treating neurotoxicity induced by Pb, and CCGA shows the strongest detoxifying activity.

Role of dietary curcumin against waterborne lead toxicity in common carp Cyprinus carpio

Curcumin exhibited numerous key activities including antioxidant, anti-inflammatory, and immunostimulatory effects in fish. This study evaluated the protective effects of curcumin (CUR) against lead (Pb)-induced toxicities in fish. Healthy Cyprinus carpio L. individuals were segregated into control, Pb only, Pb+CUR, and CUR only groups. Pb groups were exposed to 1 mg L −1 of Pb, and CUR groups were fed a basal diet supplemented with 15 g kg−1 of CUR. After eight weeks, growth performance, Pb accumulation in tissues, various haemato-biochemical parameters, immune responses, and cytokine gene expression were measured. Dietary CUR effectively decreased Pb accumulation in tissues and increased the survival of Pb-exposed fish. Co-treatment with Pb and CUR reversed alterations in haemato-biochemical parameters, ameliorated Pb-induced oxidative stress, enhanced immune responses, and restored intestinal enzymatic activities. Dietary CUR reversed changes in intestinal microbiota in Pb-exposed fish. Pb-induced upregulation of NF-κBp65 and HSP70 was inhibited by dietary CUR. CUR supplementation upregulated the mRNA levels of SOD, Nrf2, IL-10, and CYP450 1A and attenuated Pb-induced degradation of I κB-α mRNA levels. Overall, CUR antagonizes Pb-induced negative impacts in fish. Thus, dietary CUR had several beneficial effects on immune responses, decreased Pb accumulation in tissues, and reversed Pb-induced oxidative stress in fish. Therefore, CUR plays a protective role in Pb-induced immune toxicity in fish, and, as such, may be suitable as an aqua feed additive for use in carp aquaculture.