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Background: Numerous metabolic illnesses have obesity as a risk factor. The composition of the gut microbiota and endogenous metabolism are important factors in the onset and progression of obesity. Recent research indicates that cordycepin (CRD), derived from fungi, exhibits anti-inflammatory and antioxidant properties, showing potential in combating obesity. However, further investigation is required to delineate its precise impacts on endogenous metabolism and gut microbiota. Methods: In this work, male C57BL/6J mice were used as models of obesity caused by a high-fat diet (HFD) and given CRD. Mice's colon, liver, and adipose tissues were stained with H&E. Serum metabolome analysis and 16S rRNA sequencing elucidated the effects of CRD on HFD-induced obese mice and identified potential mediators for its anti-obesity effects. Results: CRD intervention alleviated HFD-induced intestinal inflammation, improved blood glucose levels, and reduced fat accumulation. Furthermore, CRD supplementation demonstrated the ability to modulate endogenous metabolic disorders by regulating the levels of key metabolites, including DL-2-aminooctanoic acid, inositol, and 6-deoxyfagomine. CRD influenced the abundance of important microbiota such as Parasutterella, Alloprevotella, Prevotellaceae_NK3B31_group, Alistipes, unclassified_Clostridia_vadinBB60_group, and unclassified_Muribaculaceae, ultimately leading to the modulation of endogenous metabolism and the amelioration of gut microbiota disorders. Conclusions: According to our research, CRD therapies show promise in regulating fat accumulation and stabilizing blood glucose levels. Furthermore, through the modulation of gut microbiota composition and key metabolites, CRD interventions have the dual capacity to prevent and ameliorate obesity. [ABSTRACT FROM AUTHOR]

Following ingestion of fruits, vegetables and derived products, (poly)phenols that are not absorbed in the upper gastrointestinal tract pass to the colon, where they undergo microbiota-mediated ring fission resulting in the production of a diversity of low molecular weight phenolic catabolites, which appear in the circulatory system and are excreted in urine along with their phase II metabolites. There is increasing interest in these catabolites because of their potential bioactivity and their use as biomarkers of (poly)phenol intake. Investigating the fate of dietary (poly)phenolics in the colon has become confounded as a result of the recent realisation that many of the phenolics appearing in biofluids can also be derived from the aromatic amino acids, l-phenylalanine and l-tyrosine, and to a lesser extent catecholamines, in reactions that can be catalysed by both colonic microbiota and endogenous mammalian enzymes. The available evidence, albeit currently rather limited, indicates that substantial amounts of phenolic catabolites originate from phenylalanine and tyrosine, while somewhat smaller quantities are produced from dietary (poly)phenols. This review outlines information on this topic and assesses procedures that can be used to help distinguish between phenolics originating from dietary (poly)phenols, the two aromatic amino acids and catecholamines.

Background: Numerous metabolic illnesses have obesity as a risk factor. The composition of the gut microbiota and endogenous metabolism are important factors in the onset and progression of obesity. Recent research indicates that cordycepin (CRD), derived from fungi, exhibits anti-inflammatory and antioxidant properties, showing potential in combating obesity. However, further investigation is required to delineate its precise impacts on endogenous metabolism and gut microbiota. Methods: In this work, male C57BL/6J mice were used as models of obesity caused by a high-fat diet (HFD) and given CRD. Mice’s colon, liver, and adipose tissues were stained with H&E. Serum metabolome analysis and 16S rRNA sequencing elucidated the effects of CRD on HFD-induced obese mice and identified potential mediators for its anti-obesity effects. Results: CRD intervention alleviated HFD-induced intestinal inflammation, improved blood glucose levels, and reduced fat accumulation. Furthermore, CRD supplementation demonstrated the ability to modulate endogenous metabolic disorders by regulating the levels of key metabolites, including DL-2-aminooctanoic acid, inositol, and 6-deoxyfagomine. CRD influenced the abundance of important microbiota such as Parasutterella, Alloprevotella, Prevotellaceae_NK3B31_group, Alistipes, unclassified_Clostridia_vadinBB60_group, and unclassified_Muribaculaceae, ultimately leading to the modulation of endogenous metabolism and the amelioration of gut microbiota disorders. Conclusions: According to our research, CRD therapies show promise in regulating fat accumulation and stabilizing blood glucose levels. Furthermore, through the modulation of gut microbiota composition and key metabolites, CRD interventions have the dual capacity to prevent and ameliorate obesity.

The SLC22 family of OATs, OCTs, and OCTNs is emerging as a central hub of endogenous physiology. Despite often being referred to as "drug" transporters, they facilitate the movement of metabolites and key signaling molecules. An in-depth reanalysis supports a reassignment of these proteins into eight functional subgroups, with four new subgroups arising from the previously defined OAT subclade: OATS1 (SLC22A6, SLC22A8, and SLC22A20), OATS2 (SLC22A7), OATS3 (SLC22A11, SLC22A12, and Slc22a22), and OATS4 (SLC22A9, SLC22A10, SLC22A24, and SLC22A25). We propose merging the OCTN (SLC22A4, SLC22A5, and Slc22a21) and OCT-related (SLC22A15 and SLC22A16) subclades into the OCTN/OCTN-related subgroup. Using data from GWAS, in vivo models, and in vitro assays, we developed an SLC22 transporter-metabolite network and similar subgroup networks, which suggest how multiple SLC22 transporters with mono-, oligo-, and multi-specific substrate specificity interact to regulate metabolites. Subgroup associations include: OATS1 with signaling molecules, uremic toxins, and odorants, OATS2 with cyclic nucleotides, OATS3 with uric acid, OATS4 with conjugated sex hormones, particularly etiocholanolone glucuronide, OCT with neurotransmitters, and OCTN/OCTN-related with ergothioneine and carnitine derivatives. Our data suggest that the SLC22 family can work among itself, as well as with other ADME genes, to optimize levels of numerous metabolites and signaling molecules, involved in organ crosstalk and inter-organismal communication, as proposed by the remote sensing and signaling theory.

Based on metabolomics, to study the mechanism of Radix Wikstroemia indica (RWI) “Sweat soaking method” processing detoxification. The raw drug group and processed products was given raw RWI and processed RWI respectively by gavage. The control group was given the same amount of 1% sodium carboxy methyl cellulose distilled water by gavage. After 7 days of continuous gavage, blood samples were collected. The blood samples of rats in each group were analyzed by ¹H-NMR technology to explore the changes of endogenous metabolism and the possible metabolic pathways to rats before and after processing. Compared with the control group, the raw RWI could significantly reduce 16 metabolites and increase 10 metabolites. The processed RWI can increase the levels of most metabolites that decrease to the raw RWI, such as 13 metabolites such as alanine, L-glutamine, L-valine, L-serine, betaine and glutamic acid; At the same time, the metabolites that increased in the level of crude products were down-regulated, such as asparagine, lactic acid, 2- hydroxyisobutyric acid, sucrose, glucose and D-glucose. Compared with raw products, RWI treated with “Sweat soaking method” can reversely regulate or reduce amino acid, choline metabolism, energy and carbohydrate metabolism, thereby reducing hepatotoxicity and nephrotoxicity. [ABSTRACT FROM AUTHOR]

The anti-hyperuricemic activity of o-methoxycinnamic acid (OMA) was investigated in the Caenorhabditis elegans (C. elegans) model, and its mode of action and biomarkers were studied using metabolomics techniques. First, a hyperuricemic C. elegans model was established to study the anti-hyperuricemic activity of OMA by altering uric acid levels in the nematodes. Subsequently, UPLC-Q-TOF/MS was used to investigate the effect of OMA on C. elegans endogenous metabolites, and differential metabolite analysis was used to identify OMA action pathways and biomarkers. The results showed that uric acid level increased by 12.0% (P

High carbon dioxide concentrations can effectively control most storage pests. To estimate the toxicity effect of high concentrations of CO2, four different concentrations of CO2 (25% CO2, 50% CO2, 75% CO2, and 95% CO2) were used to treat Tribolium castaneum, and the biochemical (carbohydrate content and gene expression level) and physiological (mortality, pupation, eclosion rate, and weight) features of insects submitted to different treatments with CO2 were evaluated. The T. castaneum mortality rate was 50% in approximately 2 days when exposed to a treatment with 95% CO2. When the CO2 concentration exceeded 75%, the pupation rate and eclosion rate of T. castaneum seriously declined. Higher than 25% CO2 concentrations resulted in a lower weight and shrunken body size of T. castaneum. It was further found that different CO2 concentration treatments all influenced the levels of the three carbohydrate contents in T. castaneum. In addition, according to the detection of trehalose metabolism pathway-related genes, T. castaneum mainly responds to stress factors via high expression of TPS, TRE1-2, and TRE1-3. Our results enrich the evaluation of the toxicity effect of CO2 treatment on grain storage pests, providing a basis for further improving the method of regulating grain storage to control insect pests. [ABSTRACT FROM AUTHOR]

Harmaine has good pharmacological activities, such as antibacterial, anti-tumor, hypoglycemic, and so on. However, harmine also has strong neurotoxicity. Exploring the neurotoxicity mechanism of harmine can help to improve the clinical application and obtain high-efficiency and low-toxic compounds in the later study. UPLC-QTOF MS technology was applied to explore the neurotoxic mechanism of harmine from the changes in Caenorhabditis elegans metabolites at different time points after administration. The results showed that harmine could mainly affect the purine metabolic pathways and amino acid-related metabolic pathways of nematodes. The neurotoxicity of harmine might be related to energy metabolism. The study can provide reference to the research of neurotoxicity of total alkaloids in Camellia pueracea. [ABSTRACT FROM AUTHOR]

High carbon dioxide concentrations can effectively control most storage pests. To estimate the toxicity effect of high concentrations of CO2, four different concentrations of CO2 (25% CO2, 50% CO2, 75% CO2, and 95% CO2) were used to treat Tribolium castaneum, and the biochemical (carbohydrate content and gene expression level) and physiological (mortality, pupation, eclosion rate, and weight) features of insects submitted to different treatments with CO2 were evaluated. The T. castaneum mortality rate was 50% in approximately 2 days when exposed to a treatment with 95% CO2. When the CO2 concentration exceeded 75%, the pupation rate and eclosion rate of T. castaneum seriously declined. Higher than 25% CO2 concentrations resulted in a lower weight and shrunken body size of T. castaneum. It was further found that different CO2 concentration treatments all influenced the levels of the three carbohydrate contents in T. castaneum. In addition, according to the detection of trehalose metabolism pathway-related genes, T. castaneum mainly responds to stress factors via high expression of TPS, TRE1-2, and TRE1-3. Our results enrich the evaluation of the toxicity effect of CO2 treatment on grain storage pests, providing a basis for further improving the method of regulating grain storage to control insect pests.

Following ingestion of fruits, vegetables and derived products, (poly)phenols that are not absorbed in the upper gastrointestinal tract pass to the colon, where they undergo microbiota-mediated ring fission resulting in the production of a diversity of low molecular weight phenolic catabolites, which appear in the circulatory system and are excreted in urine along with their phase II metabolites. There is increasing interest in these catabolites because of their potential bioactivity and their use as biomarkers of (poly)phenol intake. Investigating the fate of dietary (poly)phenolics in the colon has become confounded as a result of the recent realisation that many of the phenolics appearing in biofluids can also be derived from the aromatic amino acids, l-phenylalanine and l-tyrosine, and to a lesser extent catecholamines, in reactions that can be catalysed by both colonic microbiota and endogenous mammalian enzymes. The available evidence, albeit currently rather limited, indicates that substantial amounts of phenolic catabolites originate from phenylalanine and tyrosine, while somewhat smaller quantities are produced from dietary (poly)phenols. This review outlines information on this topic and assesses procedures that can be used to help distinguish between phenolics originating from dietary (poly)phenols, the two aromatic amino acids and catecholamines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.None, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The SLC22 family of OATs, OCTs, and OCTNs is emerging as a central hub of endogenous physiology. Despite often being referred to as “drug” transporters, they facilitate the movement of metabolites and key signaling molecules. An in-depth reanalysis supports a reassignment of these proteins into eight functional subgroups, with four new subgroups arising from the previously defined OAT subclade: OATS1 (SLC22A6, SLC22A8, and SLC22A20), OATS2 (SLC22A7), OATS3 (SLC22A11, SLC22A12, and Slc22a22), and OATS4 (SLC22A9, SLC22A10, SLC22A24, and SLC22A25). We propose merging the OCTN (SLC22A4, SLC22A5, and Slc22a21) and OCT-related (SLC22A15 and SLC22A16) subclades into the OCTN/OCTN-related subgroup. Using data from GWAS, in vivo models, and in vitro assays, we developed an SLC22 transporter-metabolite network and similar subgroup networks, which suggest how multiple SLC22 transporters with mono-, oligo-, and multi-specific substrate specificity interact to regulate metabolites. Subgroup associations include: OATS1 with signaling molecules, uremic toxins, and odorants, OATS2 with cyclic nucleotides, OATS3 with uric acid, OATS4 with conjugated sex hormones, particularly etiocholanolone glucuronide, OCT with neurotransmitters, and OCTN/OCTN-related with ergothioneine and carnitine derivatives. Our data suggest that the SLC22 family can work among itself, as well as with other ADME genes, to optimize levels of numerous metabolites and signaling molecules, involved in organ crosstalk and inter-organismal communication, as proposed by the remote sensing and signaling theory.

Background: The reported effects of flavanol-rich foods such as cocoa, dark chocolate, and apples on blood pressure and endothelial function may be due to the monomeric flavanols [mainly (-)-epicatechin (EC)], the oligomeric flavanols [procyanidins (PCs)], or other components. Reports of well-controlled intervention studies that test the effects of isolated oligomeric flavanols on biomarkers of cardiovascular health are lacking. Objective: We studied the acute and chronic effects of an ECrich apple flavanol extract and isolated apple PCs on systolic blood pressure (BP) and other cardiometabolic biomarkers. Design: Forty-two healthymen andwomenwith moderately elevated BP completed this randomized, double-blind, placebo-controlled, 4-arm crossover trial. Participants ingested a single dose of an apple flavanol extract (70 mg monomeric flavanols, 65 mg PCs), a double dose of this extract (140 mg monomeric flavanols, 130 mg PCs), an apple PC extract (130 mg PCs, 6.5 mg monomeric flavanols), or placebo capsules once daily for 4 wk, in random order. Biomarkers of cardiovascular disease risk and vascular function were measured before and 2 h after ingestion of the first dose and after the 4-wk intervention. Results: Compared with placebo, none of the isolated flavanol treatments significantly (P < 0.05) changed systolic or diastolic BP (peripheral and aortic), plasma nitric oxide (NO) reaction products, or measures of arterial stiffness (carotid femoral pulsewave velocity, brachial-ankle pulse-wave velocity, or Augmentation Index) after 2 h or 4 wk of the intervention. There were no changes in plasma endogenous metabolite profiles or circulating NO; endothelin 1; total, HDL, or LDL cholesterol; triglycerides; fasting glucose; fructosamine; or insulin after 4 wk of the intervention. Conclusions: Our data suggest that, in isolation, neither monomeric flavanols nor PCs affect BP, blood lipid profiles, endothelial function, or glucose control in individuals with moderately elevated BP. The reported benefits of consuming flavanol-rich cocoa, chocolate, and apple products appear to be dependent on other components, which may work in combination with monomeric flavanols and PCs. [ABSTRACT FROM AUTHOR]

Background Curcumin is a natural polyphenol with beneficial effects on NAFLD patients and NAFLD is accompanied by metabolism decompensation. Methods This study was focused on the effect of curcumin on the relationship between endogenous bile acids metabolism pathway and exogenous xenobiotics metabolism pathway in C57BL/6 mice of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet (HFHFr) and in cultured mice hepatocytes. Results Our results showed curcumin treatment apparently attenuated the hepatic steatosis and reversed the abnormalities of serum biochemical parameters in HFHFr-fed mice. Curcumin effectively reversed the expression of CYP3A and CYP7A in fatty liver status to restore metabolism capability. In the meantime, lipid synthesis has been controlled by curcumin, evidenced by the expression of CD36, SREBP-1c and FAS. Further, FXR, SHP and Nrf2 expressions were remarkably dropped in HFHFr-fed mice and LXRα expression was significantly enhanced, while curcumin treatment was quite effective to restore this pathway. In addition, LXRα antagonist GGPP pretreatment weakened the curcumin effects on CYP3A, CYP7A and SREBP-1c. Conclusions These findings indicate that the Nrf2/FXR/LXRα pathway might synergistically regulate both endogenous and exogenous metabolism in NAFLD mice and LXRα may be a novel therapeutic target of curcumin for the prevention and treatment of NAFLD. [ABSTRACT FROM AUTHOR]

[Display omitted] • OMA decreased the uric acid content and increased its median lethality time in nematode models. • OMA has anti-hyperuricemic activity. • OMA mainly affected the purine metabolic pathway and amino acid related metabolic pathway of nematodes. • Amino acids such as phenylalanine, alanine, tryptophan, arginine, proline and histidine can be used as potential diagnostic markers. The anti-hyperuricemic activity of o -methoxycinnamic acid (OMA) was investigated in the Caenorhabditis elegans (C. elegans) model, and its mode of action and biomarkers were studied using metabolomics techniques. First, a hyperuricemic C. elegans model was established to study the anti-hyperuricemic activity of OMA by altering uric acid levels in the nematodes. Subsequently, UPLC-Q-TOF/MS was used to investigate the effect of OMA on C. elegans endogenous metabolites, and differential metabolite analysis was used to identify OMA action pathways and biomarkers. The results showed that uric acid level increased by 12.0% (P < 0.05) in the model group, and after OMA treatment, uric acid content significantly decreased by 55.9% (P < 0.05) and prolonged median lethal time by 25% (P < 0.001), indicating anti-hyperuricemic activity of OMA. These results suggest that the mechanism may be related to abnormal regulation of amino acid metabolic pathways, using histidine and phenylalanine as potential diagnostic markers. [ABSTRACT FROM AUTHOR]

Starvation of anaerobic ammonium oxidation (anammox) bacteria can occur in underloaded bioreactors or during the storage of sludge. In this study, the impacts of intermittent and persistent resting modes and phosphates on the endogenous metabolism of anammox bacteria during long-term starvation were investigated. Batch experiments were performed to evaluate the response of anammox granules to different modes of starvation (persistent-resting and intermittent-resting cells) in the presence and absence of phosphates. The endogenous decay coefficient of anammox granules (based on the decreased biomass) over a 30-d persistent starvation period was 0.0062 d −1 , while the intermittent starvation by means of providing substrates every 10 days accelerated the biomass decay approximately twice (0.0110 d −1 ). Moreover, the intermittent-resting cells displayed exacerbated decreases in specific anammox activity relative to the persistent-resting cells, whereas no significant difference was observed in the heme c contents. Regardless of the physiological status of the cells, the presence of low levels of phosphates may be beneficial; however, a high level of phosphates is not recommended. Although different metabolic strategies were adopted depending on the starvation mode, anammox bacteria possessed a better survival strategy via a relatively low maintenance energy requirement to ensure their survival in nutrient-limited systems. In addition, the variations in extracellular protein-like components were indicative of different intracellular metabolic regulation mechanisms. These results provide a better understanding of the endogenous metabolism of anammox bacteria. [ABSTRACT FROM AUTHOR]

Introduction: The kidney is vulnerable to various injuries based on its function in the elimination of many xenobiotics, endogenous substances and metabolites. Since transporters are critical for the renal elimination of those substances, it is urgent to understand the emerging role of transporters in nephrotoxicity., Areas Covered: This review summarizes the contribution of major renal transporters to nephrotoxicity induced by some drugs or toxins; addresses the role of transporter-mediated endogenous metabolic disturbances in nephrotoxicity; and discusses the advantages and disadvantages of in vitro models based on transporter expression and function., Expert Opinion: Due to the crucial role of transporters in the renal disposition of xenobiotics and endogenous substances, it is necessary to further elucidate their renal transport mechanisms and pay more attention to the underlying relationship between the transport of endogenous substances and nephrotoxicity. Considering the species differences in the expression and function of transporters, and the low expression of transporters in general cell models, in vitro humanized models, such as humanized 3D organoids, shows significant promise in nephrotoxicity prediction and mechanism study.

Abstract: Endogenous processes such as biomass decay and intracellular polymers degradation of polyphosphate-accumulating organisms (PAOs) and glycogen-accumulating organisms (GAOs) were investigated. Cultures enriched in Accumulibacter (a well known PAO) or Competibacter (a well known GAO) were subjected to 21 and 26days of alternating anaerobic/aerobic conditions respectively. The main energy source for PAOs during starvation was their intracellular polyphosphate released into the medium during the first 14days of starvation. In contrast, GAOs used their intracellular glycogen during the 26days of starvation. Biomass decay rates were 0.029d−1 for PAOs and almost negligible for GAOs. The reduction in acetate uptake rate during the starvation period, referred to as activity decay, was 0.25 and 0.047d−1 for PAOs and GAOs, respectively. Once wastewater was reintroduced, both populations recovered their initial substrate uptake rate after 1day. The results obtained show that PAOs are more affected than GAOs by starvation conditions. [Copyright &y& Elsevier]

Abstract: The endogenous processes of Candidatus Accumulibacter phosphatis (referred to as Accumulibacter), a known polyphosphate-accumulating organism (PAO) responsible for enhanced biological phosphorus removal systems (EBPR), were characterized during 8-day starvation under anaerobic, anoxic, aerobic and intermittent aerobic–anaerobic conditions. A lab-scale EBPR culture with Accumulibacter representing over 85% of the entire bacterial population as quantified with fluorescence in-situ hybridization was used in the study. Cell decay rates were found to be negligible under anaerobic and anoxic conditions and may be ignored in activated sludge models. The decay rate under aerobic conditions was determined to be 0.03/d at 22°C, considerably lower than the values commonly used in activated sludge modeling. Polyphosphate and glycogen were utilized simultaneously under anaerobic and anoxic conditions for maintenance energy production, with glycogen being the primary energy source until the glycogen content reached very low levels. Glycogen was used by Accumulibacter as the primary source of energy for maintenance under aerobic conditions in the absence of polyhydroxyalkanoates. However, Accumulibacter did not seem to use polyphosphate for energy production during aerobic starvation, clearly contrasting the anaerobic and particularly the anoxic case. Intermittent aerobic–anaerobic storage resulted in not only negligible cell decay rate, but also slower rates of glycogen and polyphosphate utilization, and may therefore be an effective strategy for long-term storage of EBPR sludge. [Copyright &y& Elsevier]

Batch operation with different starting substrate concentrations (biological oxygen demand (BOD5)) and biomass concentrations (mixed liquor volatile solid (MLVS)) were performed on a completely mixed three-phase fluidized bed reactor used in treating simulated domestic waste water. The mixed culture microorganisms used were contained in a biofilm attaching to cement balls. The data obtained were fitted to five different kinetic rate equations. The kinetic parameters of each model were obtained using a Gauss–Newton nonlinear regression analysis method. It was found that the Haldane model incorporating endogenous metabolic consumption (Endo–Haldanc model), best described the kinetics of the biological reaction inside the three-phase fluidized bed reactor. This is due to the fact that this model can both account for the effects of cell death and/or endogenous metabolism at low concentration and of substrate inhibition at high concentration. [Copyright &y& Elsevier]

General theoretical aspects are reviewed of models for microbial growth and endogenous metabolism. The focus is on a generic cell model with two components. Growth is represented as the increase of one of these components (the structural scaffolding or 'frame'). A novel feature of the present generic model is the explicit modelling of (partial) metabolic shutdown under conditions where maintenance requirements cannot be met. Two different approaches to mechanistic underpinnings for the classic models are outlined. The first approach is based on a bimolecular reaction between the non-permanent biomass component and the permanent biomass component. The second approach is based on cellular control systems. [ABSTRACT FROM AUTHOR]

The adenosine triphosphate (ATP) content of Arthrobactery crystallopoietes was measured during growth, starvation and recovery from starvation. During exponential growth of the cells as spheres in a glucose salts medium, the level of ATP per cell remained constant at 8.0×10 μg/cell. Morphogenesis to rodshaped cells and an increased growth rate following addition of casein hydrolysate was accompanied by an almost two-fold increase in the ATP level. As division of the rod-shaped cells proceeded, the level of ATP declined. After growing as rods for 12-14 h the cells underwent fragmentation to spheres during which time the ATP level again increased to the original value of 8.0×10 μg/cell. As the spherical cells resumed growth on the residual glucose, their ATP content declined for a short period and then remained relatively constant. During starvation of sphere or rod-shaped cells for one week, the ATP level declined by approximately 70% during the first 40-50 h and then remained constant. The endogenous metabolism rate of spherical cells declined during the first 10-20 h of starvation and then remained constant at approximately 0.02% of the cell carbon being utilized per h. Addition of glucose to spherical cells which had been starved for one week increased both the ATP content per cell and their rate of endogenous metabolism. The ATP content fluctuated and then remained at a level higher than maintained during starvation while endogenous metabolism quickly declined. [ABSTRACT FROM AUTHOR]

• TCC induced ROS elevation, DNA damage and lipid peroxidation in normal hepatocytes. • Perturbations of oxidative phosphorylation and purine metabolism were ROS sources. • TCC enhanced GSH metabolism, glycolysis and glutaminolysis in cancer hepatic cells. • Metabolic activation of TCC through phase I hydroxylation was observed. • Nontargeted metabolomics reveals TCC-related endogenous and xenobiotic metabolism. Humans are frequently exposed to the antimicrobial triclocarban (TCC) due to its widespread use in consumer and personal care products. However, there is a paucity of research on potential hepatotoxic risks of TCC exposure. In this study, nontargeted metabolomics approach was applied to simultaneously investigate TCC-induced perturbation of endogenous metabolites and generation of xenobiotic metabolites in human hepatic cells. In normal hepatocytes, TCC exposure induced cellular redox imbalance as evidenced by the decrease of glutathione metabolism and overproduction of reactive oxygen species (ROS), resulting in DNA damage and lipid peroxidation. Defective oxidative phosphorylation and increased purine metabolism were two potential sources of elevated ROS. However, in cancerous hepatocytes, TCC exposure enhanced glutathione metabolism, glycolysis, and glutaminolysis, which contributed to the cellular homeostasis of redox and energy status, as well as the progression of liver cancer. As a xenobiotic, metabolic activation of TCC through phase I hydroxylation was observed. The hepatic cytotoxicity follows the order of 6-OH-TCC > 2'-OH-TCC > 3'-OH-TCC > DHC, with EC 50 values of 2.42, 3.38, 7.38, and 24.8 μM, respectively, in 48 h-treated normal cells. This study improves current understanding of TCC-triggered hepatotoxicity, and provides novel perspectives for evaluating the interaction of environmental pollutants with biological systems. [ABSTRACT FROM AUTHOR]

Background: Cytochrome P450 2S1 (CYP2S1) is one of the 'orphan' CYPs, which is expressed primarily among extra-hepatic tissues and it is inducible by dioxin. Although the contribution of extra-hepatic CYPs in drug metabolism is considered less significant, they play more important roles in leading to in situ toxicity in organs with higher expression., Method: A non-systemic search was performed to review articles relevant to CYP2S1 in literature. This review will update the findings related to the expression and regulation of CYP2S1 gene and protein, substrate profiles and metabolism mechanisms, genetic polymorphisms, and their association with diseases., Results: The expression of CYP2S1 was mainly in the epithelium of portal of entry organs such as respiratory and gastrointestinal tract. Aryl Hydrocarbon Receptor (AHR) is believed to be partly involved in the induction of CYP2S1. CYP2S1 was found to activate and deactivate pro-drugs which resulted in toxicity and detoxification of carcinogens. The current knowledge of the endogenous functions of CYP2S1 is largely related to cell proliferation and lipid metabolisms. Several polymorphic alleles of CYP2S1 have been reported and documented to date., Conclusion: Molecular-based investigations should be performed to better understand the regulation mechanism of CYP2S1 in various cells and tissues. It is pivotal to establish optimum expression and incubation systems in vitro to elucidate the substrate specificity of CYP2S1 and characterise the genetic consequences of variant CYP2S1 in vitro., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)