Oxidative stress, metallomics and blood toxicity after subacute low-level lead exposure in Wistar rats: Benchmark dose analyses

Javorac, Dragana; Antonijević, Biljana; Anđelković, Milena; Repić, Aleksandra; Bulat, Petar; Djordjević, Aleksandra Buha; Baralić, Katarina; Đukić-Ćosić, Danijela; Antonić, Tamara; Bulat, Zorica

doi:10.1016/j.envpol.2021.118103

Cited by 23 publications

(19 citation statements)

References 76 publications

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“…However, no concentration–response relationship between the iron level and exposure level was observed. This phenomenon was consistent with the change of iron content in rats after metal exposure . The occurrence of ferroptosis may be related to the disorder of iron homeostasis caused by metals …”

Section: Resultssupporting

confidence: 85%

“…This phenomenon was consistent with the change of iron content in rats after metal exposure. 54 The occurrence of ferroptosis may be related to the disorder of iron homeostasis caused by metals. 52 SLC7A11 and SLC3A2 genes encode cystine/glutamate antiporter, which regulates intracellular glutathione production to prevent ferroptosis.…”

Section: Apoptosis and Ferroptosismentioning

confidence: 99%

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Elucidating the Differences in Metal Toxicity by Quantitative Adverse Outcome Pathways

Yang

Zeng

Gao

et al. 2022

Environ. Sci. Technol.

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Numerous studies have reported that the toxicity differences among metals are widespread; however, little is known about the mechanism of differences in metal toxicity to aquatic organisms due to the lack of quantitative understanding of their adverse outcome pathway. Here, we investigated the effects of Cd and Cu on bioaccumulation, gene expression, physiological responses, and apical effects in zebrafish larvae. RNA sequencing was conducted to provide supplementary mechanistic information for the effects of Cd and Cu exposure. On this basis, we proposed a quantitative adverse outcome pathway (qAOP) suitable for metal risk assessment of aquatic organisms. Our work provides a mechanistic explanation for the differences in metal toxicity where the strong bioaccumulation of Cu enables the newly accumulated Cu to reach the threshold that causes different adverse effects faster than Cd in zebrafish larvae, resulting in a higher toxicity of Cu than that of Cd. Furthermore, we proposed a parameter C IT/BCF (the ratio of internal threshold concentration and bioaccumulation factor) that helps to understand the toxicity differences by combining the information of bioaccumulation and internal threshold of adverse effects. This work demonstrated that qAOP is an effective quantitative tool for understanding the toxicity mechanism and highlight the importance of toxicokinetics and toxicodynamics at different biological levels in determining the metal toxicity.

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Section: Resultssupporting

confidence: 85%

Section: Apoptosis and Ferroptosismentioning

confidence: 99%

Elucidating the Differences in Metal Toxicity by Quantitative Adverse Outcome Pathways

Yang

Zeng

Gao

et al. 2022

Environ. Sci. Technol.

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“…The finding of this study demonstrated that the level of SOD, GSH, GPx, and CAT was decreased in the Pb-intoxicated mice group and was responsible for oxidative stress in mice, as the same has also been reported in some previous studies ( Wang et al, 2013 ; Javorac et al, 2021 ). The levels of SOD, GSH, GPx, and CAT were increased in the Pb + Q-CRN group because of the antioxidant activity of bioflavonoid quercetin as already reported in previous studies ( Crown et al, 2019 ; Akinmoladun et al, 2020 ).…”

Section: Discussionsupporting

confidence: 90%

“…Blood Pb toxicity is also responsible for disturbing the heme biosynthetic In the blood, Pb inhibits δ-aminolevulinic acid dehydratase (ALAD), and thus the concentration of aminolevulinic acid (ALA) is increased in the blood, which leads to oxidative stress in the body (Qader et al, 2021). It was presumed that the high level of ALA was responsible for increasing the level of MDA in Pb-intoxicated mice (Wang et al, 2013;Kasperczyk et al, 2015;Javorac et al, 2021). However, the level of MDA was restored in the Pb + Q-CRN group because of the antioxidant activity of bioflavonoid quercetin, as also confirmed in previous studies (Crown et al, 2019;Akinmoladun et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Lead increases the level of reactive oxygen species (superoxide (O 2- ), hydroperoxide (−O−O−H), and hydrogen peroxide (H 2 O 2 ) and leads to alteration in lipid metabolism, DNA damage, gene expression, membrane integrity, and different physiological processes ( Balali-Mood et al, 2021 ). Lead can also interfere with the synthetic pathway of heme, and thus it is also responsible for anemia ( Rehman et al, 2018 ; Javorac et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Biochemical profiling of metabolomics in heavy metal-intoxicated impaired metabolism and its amelioration using plant-based bioactive compound

Yaqoob

Rehman

Akash

et al. 2022

Front. Mol. Biosci.

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Exposure to Pb is widely spreading and has far-reaching negative effects on living systems. This study aimed to investigate the toxic effects of Pb, through biochemical profiling and the ameliorative effects of quercetin against Pb-toxicity. Twenty-five male Wistar albino mice were divided into the following five groups. The CON-group received normal saline; the Pb-group received PbAc; the Pb + Q-CRN group received lead acetate followed by quercetin; the Q-CRN group received quercetin; and the CRN group received corn oil. After 4 weeks, the mice were euthanized. It was speculated that Pb significantly increased the levels of serine, threonine, and asparagine and decreased the levels of valine, lysine, and glutamic acid in the plasma of Pb-group, thus impairing amino acid metabolism. However, in the Pb + Q-CRN group, the level of these six amino acids was restored significantly due to the ameliorative effect of quercetin. The presence of lipid metabolites (L-carnitine, sphinganine, phytosphingosine, and lysophosphatidylcholine) in mice serum was confirmed by ESI/MS. The GPx, SOD, GSH, and CAT levels were significantly decreased, and the MDA level was significantly increased, thus confirming the oxidative stress and lipid peroxidation in the Pb group. The antioxidant effect of quercetin was elucidated in the Pb + Q-CRN group. Expression of CPT-I, CPT-II, LCAT, CROT, CACT, and MTR genes was significantly upregulated in the liver of Pb goup mice. Hence, the findings of this study proved that Pb exposure induced oxidative stress, upregulated gene expression, and impaired the lipid and amino acid metabolism in mice.

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Possible role of lead in breast cancer — a case-control study

Anđelković

Djordjević

Javorac

et al. 2022

Environ Sci Pollut Res

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Oxidative stress, metallomics and blood toxicity after subacute low-level lead exposure in Wistar rats: Benchmark dose analyses

Cited by 23 publications

References 76 publications

Elucidating the Differences in Metal Toxicity by Quantitative Adverse Outcome Pathways

Elucidating the Differences in Metal Toxicity by Quantitative Adverse Outcome Pathways

Biochemical profiling of metabolomics in heavy metal-intoxicated impaired metabolism and its amelioration using plant-based bioactive compound

Possible role of lead in breast cancer — a case-control study

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