Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

Fordahl, Steve C.; Cooney, Paula T.; Qiu, Yunping; Xie, Guoxiang; Wang, Jia; Erikson, Keith M.

doi:10.1016/j.ntt.2011.10.003

Cited by 41 publications

(40 citation statements)

References 55 publications

(67 reference statements)

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“…28 GI contents (100 mg) were mixed with 500 µL of ice-cold water. The mixture was vortexed for 4 min and then centrifuged at 13,200 rpm at 4 °C for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Chronic Ethanol Consumption Alters Mammalian Gastrointestinal Content Metabolites

et al. 2013

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Chronic ethanol consumption is not only associated with the alteration of metabolic profiles in biofluids, but also the composition of the gut microbiome. Our understanding of the importance of the intestinal microbiota as well as the disturbances elicited by ethanol intervention is limited by the fact that previous analyses have primarily focused on biofluids and liver tissue metabolome; the metabolic profiles of the gastrointestinal (GI) contents are rarely investigated. In this study, we applied a metabonomics approach using a high performance liquid chromatography time of flight mass spectrometry (HPLC-TOFMS) and gas chromatography mass spectrometry (GC-MS) to characterize the metabolic alterations of the contents within the GI tract (stomach, duodenum, jejunum, ileum, cecum, colon, and rectum) in male Sprague Dawley rats following 8 weeks ethanol exposure. We obtained a snapshot of the distinct changes of the intestinal content metabolite composition in rats with ethanol exposure, which indicated a profound impact of ethanol consumption on the intestinal metabolome. Many metabolic pathways that are critical for host physiology were affected, including markedly altered bile acids, increased fatty acids and steroids, decreased carnitines and metabolites involved in lipid metabolism, a significant decrease of all amino acids and branched chain amino acids, and significantly decreased short chain fatty acids except for acetic acid which rapidly elevated as a product of ethanol metabolism. These results provide an improved understanding of the systemic alteration of intestinal metabolites in mammals and the interplay between the host and its complex resident microbiota, and may aid in the design of new therapeutic strategies that target these interactions.

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“…28 GI contents (100 mg) were mixed with 500 µL of ice-cold water. The mixture was vortexed for 4 min and then centrifuged at 13,200 rpm at 4 °C for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Chronic Ethanol Consumption Alters Mammalian Gastrointestinal Content Metabolites

et al. 2013

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“…Two aliquots of 150 μl of supernatant were combined into the tube containing first step extraction for GC and LC-TOFMS analysis, separately. Metabolite annotation was performed by comparing the mass spectrum and retention time to an in-house library and NIST library (GC-TOMFS) or HMDB (LC-TOFMS) [25,26]. …”

Section: Methodsmentioning

confidence: 99%

Obesity increases tumor aggressiveness in a genetically engineered mouse model of serous ovarian cancer

Makowski

Zhou

Zhong

et al. 2014

Gynecologic Oncology

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Objectives Obesity is associated with increased risk and worse outcomes for ovarian cancer. Thus, we examined the effects of obesity on ovarian cancer progression in a genetically engineered mouse model of serous ovarian cancer. Methods We utilized a unique serous ovarian cancer mouse model that specifically deletes the tumor suppressor genes, Brca1 and p53, and inactivates the retinoblastoma (Rb) proteins in adult ovarian surface epithelial cells, via injection of an adenoviral vector expressing Cre (AdCre) into the ovarian bursa cavity of adult female mice (KpB mouse model). KpB mice were subjected to a 60% calories-derived from fat in a high fat diet (HFD) versus 10% calories from fat in a low fat diet (LFD) to mimic diet-induced obesity. Tumors were isolated at 6 months after AdCre injection and evaluated histologically. Untargeted metabolomic and gene expression profiling was performed to assess differences in the ovarian tumors from obese versus non-obese KpB mice. Results At sacrifice, mice on the HFD (obese) were twice the weight of mice on the LFD (non-obese) (51 g versus 31 g, p = 0.0003). Ovarian tumors were significantly larger in the obese versus non-obese mice (3.7 cm2 versus 1.2 cm2, p = 0.0065). Gene expression and metabolomic profiling indicated statistically significant differences between the ovarian tumors from the obese versus non-obese mice, including metabolically relevant pathways.

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“…The ES+ and ES- raw data generated from HPLC-TOFMS was analyzed by MassHunter Qualitative Analysis Program (vB.05.01, Agilent, Santa Clara, CA) [21], [23]. The resulting data from the HPLC-TOFMS platforms were subjected to multivariate statistical analyses to establish characteristic metabolomic profiles associated with different groups.…”

Section: Methodsmentioning

confidence: 99%

High Fat Diet Feeding Exaggerates Perfluorooctanoic Acid-Induced Liver Injury in Mice via Modulating Multiple Metabolic Pathways

et al. 2013

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High fat diet (HFD) is closely linked to a variety of health issues including fatty liver. Exposure to perfluorooctanoic acid (PFOA), a synthetic perfluorinated carboxylic acid, also causes liver injury. The present study investigated the possible interactions between high fat diet and PFOA in induction of liver injury. Mice were pair-fed a high-fat diet (HFD) or low fat control with or without PFOA administration at 5 mg/kg/day for 3 weeks. Exposure to PFOA alone caused elevated plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels and increased liver weight along with reduced body weight and adipose tissue mass. HFD alone did not cause liver damage, but exaggerated PFOA-induced hepatotoxicity as indicated by higher plasma ALT and AST levels, and more severe pathological changes including hepatocyte hypertrophy, lipid droplet accumulation and necrosis as well as inflammatory cell infiltration. These additive effects of HFD on PFOA-induced hepatotoxicity correlated with metabolic disturbance in liver and blood as well as up-regulation of hepatic proinflammatory cytokine genes. Metabolomic analysis demonstrated that both serum and hepatic metabolite profiles of PFOA, HFD, or HFD-PFOA group were clearly differentiated from that of controls. PFOA affected more hepatic metabolites than HFD, but HFD showed positive interaction with PFOA on fatty acid metabolites including long chain fatty acids and acylcarnitines. Taken together, dietary high fat potentiates PFOA-induced hepatic lipid accumulation, inflammation and necrotic cell death by disturbing hepatic metabolism and inducing inflammation. This study demonstrated, for the first time, that HFD increases the risk of PFOA in induction of hepatotoxicity.

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Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

Cited by 41 publications

References 55 publications

Chronic Ethanol Consumption Alters Mammalian Gastrointestinal Content Metabolites

Chronic Ethanol Consumption Alters Mammalian Gastrointestinal Content Metabolites

Obesity increases tumor aggressiveness in a genetically engineered mouse model of serous ovarian cancer

High Fat Diet Feeding Exaggerates Perfluorooctanoic Acid-Induced Liver Injury in Mice via Modulating Multiple Metabolic Pathways

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