Lead exposure induces metabolic reprogramming in rat models

Mani, Monica Shirley; Joshi, Manjunath B.; Shetty, Rashmi; Dsouza, Venzil Lavie; Swathi, M; Kabekkodu, Shama Prasada; Dsouza, Herman Sunil

doi:10.1016/j.toxlet.2020.09.010

Cited by 23 publications

(8 citation statements)

References 74 publications

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“…Middle-chain fatty acids are able to enter mitochondria with and without passing the carnitine transport system 55 . Due to β-oxidation cycle disturbances, discussed above, there is a deficit of carnitine in mitochondria, so a non-carnitine way for middle chain acid was more preferable -a lack of free carnitine was also observed in the other lead intoxication study 49 . This fact explains the reduced concentration of 4-decenoylcarnitine in lead-exposed group in comparison to the control group.…”

Section: Metabolomic Studymentioning

confidence: 83%

“…Acylcarnitines are known biomarkers of mitochondria dysfunction and oxidative stress 46,47 ; they are also described as inflammation inductors 48 . Previous metabolomic studies of lead toxicity are not numerous and mention changes in amino acids, lipid metabolism, and in the concentrations of short-and long-chain acylcarnitines, diacylglycerols, and sphingomielins 9,13,49 . The results of our study agree with these previous studies, as we also observed an increase in the blood concentration of acylcarnitines.…”

Section: Metabolomic Studymentioning

confidence: 99%

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Blood metabolic fingerprinting of rats, subjected to subchronic lead exposure

Chemezov¹,

Sutunkova²,

Minigalieva³

et al. 2021

Public Health Toxicol

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INTRODUCTION Environmental pollution with heavy metals is vital issue in the present time. Lead, as one of the environmental contaminators, deserves attention due to its applicability in human activity and its xenobiotic character. METHODS In this study we used an untargeted metabolomic approach -the metabolomic fingerprinting method. Lead acetate was intraperitoneally injected to rats within the framework of a subchronical experiment and blood samples were analyzed by UHPLC-MS. Metabolite expression was qualitatively compared between treated and control groups. For substances with a significant content difference, tandem CID spectra for structure elucidation were obtained using an exact mass search by generating a list of potential formulas, by a characteristic fragments database search, using in silico mass spectra prediction, and by looking for a specific fragmentation rearrangement. RESULTS Untargeted metabolomic analysis shows 37 metabolites with significant changes in expression in comparing the control and exposure group. Annotation

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Section: Metabolomic Studymentioning

confidence: 83%

Section: Metabolomic Studymentioning

confidence: 99%

Blood metabolic fingerprinting of rats, subjected to subchronic lead exposure

Chemezov¹,

Sutunkova²,

Minigalieva³

et al. 2021

Public Health Toxicol

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“…In a study investigating the effects of Pb exposure on the gut microbiome and blood metabolome in 8-week-old female mice, Gao et al found that Pb exposure altered multiple metabolomic pathways including nitrogen metabolism, oxidative stress, vitamin E, and bile acids (10). A similar dosing study in 8-month-old rats found that Pb exposure reduced levels of butyryl-L-carnitine and ganglioside GD2 (d18:0/20:0) and increased levels of metabolites associated with oxidative stress pathways (11). In an epidemiologic investigation of the urinary metabolome of highly-exposed participants residing near a Pb acid battery recycling plant, blood Pb was associated with several metabolic pathways, including porphyrin, amino acid, and chlorophyll metabolism, heme biosynthesis, and ATP-binding cassette transporters (12).…”

Section: Introductionmentioning

confidence: 99%

Lead exposure and serum metabolite profiles in pregnant women in Mexico City

Niedzwiecki

Eggers

Joshi

et al. 2021

Preprint

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Background: Lead (Pb) exposure is a global health hazard causing a wide range of adverse health outcomes. Yet, the mechanisms of Pb toxicology remain incompletely understood, especially during pregnancy. To uncover biological pathways impacted by Pb exposure, this study investigated serum metabolomic profiles during the third trimester of pregnancy that are associated with blood Pb and bone Pb. Methods: We used data and specimens collected from 99 women enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort based in Mexico City. Maternal Pb exposure was measured in whole blood samples from the third trimester of pregnancy and in the tibia and patella bones at 1 month postpartum. Third-trimester serum samples underwent metabolomic analysis; metabolites were identified based on matching to an in-house analytical standard library. A metabolome-wide association study was performed with all three Pb measurements using multiple linear regression models, adjusted for confounders and batch effects. Class enrichment analyses were also conducted. Results: The median (interquartile range) blood Pb concentration was 2.9 (2.6) μg/dL. Median bone Pb, measured in the patella and tibia, were 2.5 (7.3) μg/g and 3.6 (9.5) μg/g, respectively. Of 248 total metabolites identified in serum, 31 were associated with blood Pb (p<0.05). Class enrichment analysis identified significant overrepresentation of metabolites classified as fatty acids and conjugates, amino acids and peptides, and purines. Tibia and patella Pb were associated with 14 and 11 metabolites, respectively (p<0.05). Comparing results from bone and blood Pb, glycochenodeoxycholic acid and glycocholic acid were negatively associated with blood Pb and tibia Pb, while 5-aminopentanoic acid and 7-methylguanine were negatively associated with blood Pb and patella Pb. One metabolite, 5-aminopentanoic acid, was associated with all three Pb measures. Conclusion: This study identified serum metabolites in pregnant women associated with Pb measured in blood (31 metabolites) and bone (tibia: 14 metabolites, patella: 11 metabolites). These findings provide insights on the metabolic profile around Pb exposure in pregnancy and may provide important links to guide detailed studies of toxicological effects for both mothers and children.

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“…For Pb, some metabolomics studies have been conducted on humans using the serum of smelter workers [ 9 ], urine of a population living near a Pb-containing battery recycling plant [ 10 ], plasma of car commuters [ 11 ], and urine from children and elderly individuals living in an industrial coking area [ 12 ]. Other studies investigated the metabolic alteration in laboratory rat serum [ 13 ] and laboratory mouse feces [ 14 ]. However, there is no previous report examining terrestrial field animals environmentally exposed to Pb.…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Alteration in the Plasma of Wild Rodents Environmentally Exposed to Lead: A Preliminary Study

Nakata

Eguchi

Nakayama

et al. 2022

IJERPH

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Lead poisoning is often considered a traditional disease; however, the specific mechanism of toxicity remains unclear. The study of Pb-induced alterations in cellular metabolic pathways is important to understand the biological response and disorders associated with environmental exposure to lead. Metabolomics studies have recently been paid considerable attention to understand in detail the biological response to lead exposure and the associated toxicity mechanisms. In the present study, wild rodents collected from an area contaminated with lead (N = 18) and a control area (N = 10) were investigated. This was the first ever experimental metabolomic study of wildlife exposed to lead in the field. While the levels of plasma phenylalanine and isoleucine were significantly higher in a lead-contaminated area versus the control area, hydroxybutyric acid was marginally significantly higher in the contaminated area, suggesting the possibility of enhancement of lipid metabolism. In the interregional least-absolute shrinkage and selection operator (lasso) regression model analysis, phenylalanine and isoleucine were identified as possible biomarkers, which is in agreement with the random forest model. In addition, in the random forest model, glutaric acid, glutamine, and hydroxybutyric acid were selected. In agreement with previous studies, enrichment analysis showed alterations in the urea cycle and ATP-binding cassette transporter pathways. Although regional rodent species bias was observed in this study, and the relatively small sample size should be taken into account, the present results are to some extent consistent with those of previous studies on humans and laboratory animals.

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Lead exposure induces metabolic reprogramming in rat models

Cited by 23 publications

References 74 publications

Blood metabolic fingerprinting of rats, subjected to subchronic lead exposure

Blood metabolic fingerprinting of rats, subjected to subchronic lead exposure

Lead exposure and serum metabolite profiles in pregnant women in Mexico City

Metabolomic Alteration in the Plasma of Wild Rodents Environmentally Exposed to Lead: A Preliminary Study

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