|
 
 |
| ORIGINAL ARTICLE |
|
| Year : 2019 | Volume
: 4
| Issue : 3 | Page : 62-68 |
|
PM2.5inhalation aggravates inflammation, oxidative stress, and apoptosis in nonalcoholic fatty liver disease
Shen Xin1, Jing Qu2, Na Xu2, Baohong Xu1
1 Department of Gastroenterology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
2 Department of Geriatric Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| Date of Submission | 10-Jun-2019 |
| Date of Acceptance | 15-Jul-2019 |
| Date of Web Publication | 27-Sep-2019 |
Correspondence Address:
Dr. Baohong Xu
Department of Gastroenterology, Beijing Luhe Hospital, Capital Medical University, Beijing 101149
China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ed.ed_24_19
Background: Particulate matter under 2.5 μm (PM2.5) is a major risk factor for nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate whether PM2.5could aggravate NAFLD, as well as its relative mechanisms.
Materials and Methods: Male Sprague-Dawley rats were under PM2.5exposure and filtered air with NAFLD for 4, 6, and 8 weeks. Blood lipids were measured by enzyme-linked immunosorbent assay (ELISA). The histopathology of liver was determined by hematoxylin and eosin staining. ELISA assay was conducted for detecting inflammatory markers including interleukin-17 (IL-17) or tumor necrosis factor alpha (TNF-α) and for assessing oxidative stress-associated proteins, including superoxide dismutase (SOD) and malondialdehyde (MDA). Apoptosis was assessed by detecting B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (BAX) by real-time polymerase chain reaction and Western blotting.
Results: PM2.5exposure for 8 weeks, but not 4 or 6 weeks, significantly aggravated NAFLD, which was associated with the enhanced expression of IL-17 and TNF-α and the enhanced oxidative stress (SOD and MDA). Meanwhile, exposure PM2.5for 8 weeks, but not 4 or 6 weeks, regulated apoptosis (Bcl-2 and BAX).
Conclusions: Exposure of PM2.5for 8 weeks can aggravate NAFLD, which may be mediated by liver inflammation, oxidative stress, and apoptosis.
Keywords: Apoptosis, inflammation, nonalcoholic fatty liver disease, oxidative stress
How to cite this article:
Xin S, Qu J, Xu N, Xu B. PM2.5inhalation aggravates inflammation, oxidative stress, and apoptosis in nonalcoholic fatty liver disease. Environ Dis 2019;4:62-8 |
How to cite this URL:
Xin S, Qu J, Xu N, Xu B. PM2.5inhalation aggravates inflammation, oxidative stress, and apoptosis in nonalcoholic fatty liver disease. Environ Dis [serial online] 2019 [cited 2023 Jun 5];4:62-8. Available from: http://www.environmentmed.org/text.asp?2019/4/3/62/268151 |
| Introduction | |  |
Environmental quality has recently become a major focus around the world. Currently, air pollution has gradually developed as one of the most serious threats to health, especially in China.[1],[2] A previous study has proved that the main air pollution compound was particulate matter under the size of 2.5 μm (PM2.5), also called woomay. Because of their small size, PM2.5 can delve into the respiratory system and may enter thence into the bloodstream, destroying the blood–brain barrier. Hence, PM2.5 may distribute elsewhere in the body to participate in many deleterious processes. Numerous studies have previously demonstrated that PM2.5 is related to respiratory, digestive, cardiovascular,[3],[4] and cerebrovascular diseases,[5],[6] which leads to dysarteriotony, insulin resistance,[7] inflammatory response,[8],[9] and neuroinflammation.[10],[11]
Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic fat accumulation in the absence of significant alcohol consumption,[12],[13],[14],[15],[16] is one of the public health concerns.[17] The etiology of NAFLD is very complicated; the risk factors include smoking, hyperlipidemia, hypertension, and lack of exercise. Previous studies illustrated that abnormal upregulation of oxidative stress, inflammation, and apoptosis could aggravate hepatic dyslipidemia and lipid accumulation, ultimately promoting the development of NAFLD.[18],[19],[20],[21] A recent study demonstrated that elevated PM2.5 concentration was associated with first hospital admissions for NAFLD.[22] In addition, Xu et al. found that PM2.5 exposure could upregulate cholesterol and triglyceride (TG) of serum and liver tissues, leading to hepatic dyslipidemia, which suggested that air pollution might contribute to the risk of NAFLD.[23] However, the underlying mechanism of PM2.5 aggravating the development of NAFLD remains unclear. Therefore, we aimed to gain insight into the potential mechanisms by which long-term PM2.5 exposure contributes to the development of NAFLD in this study.
| Materials and Methods | | |
Animals and PM2.5-exposure designs
The protocol was approved by the Animal Care and Use Committee of the Capital Medical University, and the study was conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (USA). Sixty male Sprague-Dawley rats (280–320 g) were randomly divided into PM2.5 and filtered air (FA) group. All the rats were fed with a high-fat diet for up to 4, 6, and 8 weeks.[24] The PM2.5 rats were exposed to a PM2.5-exposure system, and the FA rats were exposed to an environment without PM2.5 filtered by an air strainer.[25] The rats in the exposure chamber were housed under controlled temperature (22°C ± 2°C) and humidity (40%–60%) conditions with a 12 h light/dark cycle.
Histopathology
Rats' liver tissues were cut into 4 μm-thick slices and stained with hematoxylin and eosin (HE) after perfusing and fixing according to our previous study. The extent of hepatocyte injury was then determined under light microscopy (Carl Zeiss, Jena, Germany).[23] The ratio of injured hepatocytes to the total hepatocytes was calculated; cell injury was indicated by the presence of swelling and vacuolar degeneration. To quantify the severity of hepatic injury, a point counting method on an ordinal scale was used, as described.[26]
Serum biochemistry and liver cytokines
Serum was collected from all groups and was measured with the COBAS Integra 800 analyzer (COBAS, Mannheim, Germany) using enzyme-linked immunosorbent assay (ELISA) for the detection of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and TG in rats.[26] Furthermore, liver levels of interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by ELISA.
RNA assay
TRIzol reagent (Invitrogen, California, USA) was used for extracting total liver RNA.[23] Then, the complementary DNA was amplified by real-time polymerase chain reaction (Applied Biosystems, CA, USA) according to our previous procedure: 95°C for 15 min, 95°C for 10 s, and 60°C for 30 s of 40 cycles. The cycle time was normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the same sample. The primers for rat B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (BAX), and GAPDH are summarized in [Table 1].
Western blotting
The isolated liver tissues were conducted for analysing protein expression by Western blotting, as described.[27],[28] Primary antibodies, including anti-Bcl-2 (1:2000, ab196495, Abcam, Cambridge, MA, USA), anti-BAX (1:2000, ab77566, Abcam, Cambridge, MA, USA), and anti-β-actin (1:2000, G1001, Guanxingyu, Beijing, China), were incubated on the polyvinylidene fluoride membrane for 24 h at 4°C. The membranes were then washed three times with phosphate-buffered saline and reincubated in secondary antibody for 1 h at room temperature. An enhanced chemiluminescence system was used to detect immunoreactive bands. Western blotting images for each antibody were analyzed using an image analysis program (ImageJ V1.42q, software, National Institutes of Health, Bethesda, MD, USA) to quantify protein expression in terms of relative image density.
Statistical analyses
Statistical analyses were performed with SPSS Statistics for Windows, Version 17.0 (SPSS Inc., Chicago, IL, USA). Differences among groups were assessed using one-way ANOVA with a statistical significance level of P < 0.05. Post hoc comparison among groups was performed using the least significant difference method.
| Results | | |
PM<2.5decreased rats' body weight
During PM2.5 exposure, rats' body weight was recorded every week. A significant decrease in body weight could be found in PM2.5-exposure groups for 4, 6, or 8 weeks [Figure 1]. | Figure 1: Effects of PM2.5exposure on body weight. Body weight after 4, 6, and 8 weeks of PM2.5exposure is shown. Data are presented as mean ± standard error; *P < 0.05, n = 10
Click here to view |
PM2.5significantly aggravated liver histology
To determine whether PM2.5 exposure could aggravate hepatic dyslipidemia, the liver tissues were stained by HE. As shown in [Figure 2], PM2.5 reduced the damaged hepatocyte ratio, which was determined by the presence of severe swelling and vacuolar degeneration in liver. | Figure 2: Effects of PM2.5exposure on liver histology. (a) Representative photomicrographs of hematoxylin and eosin staining of liver after 4, 6, and 8 weeks of PM2.5exposure are shown. (b) The hepatocyte death ratio after 4, 6, and 8 weeks of PM2.5exposure is shown. Values are presented as mean ± standard error, *P < 0.05, n = 5
Click here to view |
PM2.5aggravated serum biochemical abnormalities
To observe the liver functions' exposure in PM2.5, serum biochemical criteria were examined. An increasing serum level of ALT, AST, TG, TC, and LDL and a decreasing serum level of HDL could be found in PM2.5 exposure, as shown in [Figure 3]. AST levels (U/L) increased from ~120 to ≥150 after 4 weeks, and similar results were noted after 6 and 8 weeks. ALT levels (U/L) increased from ~40 to ≥50 after 4 weeks and from ~60 to ≥80 after 6 and 8 weeks. TG levels (mmol/L) increased from 1.0 to about 1.4 after 4 weeks and 6 weeks and from 1.3 to about 1.7 after 8 weeks. TC levels (mmol/L) increased from ~1.7 to about 2.3 after 4 weeks, and similar results were noted after 6 and 8 weeks. HDL levels (mmol/L) decreased from 0.7 to about 0.4 after 4 weeks and from 0.9 to 0.5 after 8 weeks. LDL levels (mmol/L) increased from 0.5 to about 0.9 after 4 weeks and from 0.6 to 0.8 after 6 and 8 weeks. | Figure 3: Effects of PM2.5exposure on blood lipids. Aspartate aminotransferase, alanine aminotransferase, triglyceride, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol levels after 4, 6, and 8 weeks of PM2.5exposure are shown. Values are presented as mean ± standard error, *P < 0.05, **P < 0.01, n = 10
Click here to view |
PM2.5stimulated liver inflammatory response
To observe the relative inflammatory molecular response for NAFLD after PM2.5 exposure, inflammatory cytokines collected from liver tissues after 4, 6, and 8 weeks were measured by Western blotting. PM2.5 observably increased the protein expression of IL-17 or TNF-α compared to FA after 8 weeks [Figure 4]. | Figure 4: Effects of PM2.5exposure on the expression of interleukin-17 and tumor necrosis factor-alpha in liver. The expression of interleukin-17 (a) and tumor necrosis factor-alpha (b) after 4, 6, and 8 weeks of PM2.5exposure was detected by enzyme-linked immunosorbent assay. Data are presented as mean ± standard error, *P < 0.05, n = 5
Click here to view |
PM2.5decreased superoxide dismutase activity and increased malondialdehyde level
Subsequently, we observed the expression of SOD and MDA after PM2.5 exposure. As shown in [Figure 5], PM2.5 observably reduced the protein expression of SOD and enhanced the protein expression of MDA as compared to FA after 8 weeks. | Figure 5: Effects of PM2.5exposure on the expression of superoxide dismutase and malondialdehyde in liver. The expression of superoxide dismutase (a) and malondialdehyde (b) after 4, 6, and 8 weeks of PM2.5exposure was detected by enzyme-linked immunosorbent assay. Data are presented as mean ± standard error, *P < 0.05, n = 5
Click here to view |
PM2.5increased apoptosis
To investigate the effect of PM2.5 on apoptosis, the protein expressions of Bcl-2 and BAX were examined. As shown in [Figure 6]a and [Figure 6]b, PM2.5 obviously reduced the mRNA expression of Bcl-2 and elevated the mRNA expression of BAX after 8 weeks as compared to FA. Then, we detected the protein levels of Bcl-2 and BAX by Western blotting analyses; similar diagram forms of Bcl-2 and BAX expression could be found in [Figure 6]c and [Figure 6]d. PM2.5 obviously reduced the protein expression of Bcl-2 and elevated the protein expression of BAX after 8 weeks as compared to FA. | Figure 6: Effects of PM2.5exposure on the expression of B-cell lymphoma-2 and Bcl-2-associated X protein in liver. The mRNA expression of B-cell lymphoma-2 (a) and Bcl-2-associated X protein (b) and protein levels of B-cell lymphoma-2 (c) and Bcl-2-associated X protein (d) after 4, 6, and 8 weeks of PM2.5exposure were detected by real-time polymerase chain reaction and Western blotting analyses, respectively. Data are presented as mean ± standard error, *P < 0.05, **P < 0.01, n = 5
Click here to view |
| Discussion | | |
In this study, we explored the mechanism of PM2.5 exposure which aggravates the progress of NAFLD. We found that long-term PM2.5 inhalation could induce inflammation, oxidative stress, and apoptosis in NAFLD rats. Our findings mainly include (1) PM2.5 exposure for 8 weeks can induce inflammation (IL-17 and TNF-α); (2) PM2.5 could increase liver oxidative stress (the reduced expression of SOD and the elevated expression of MDA); and (3) PM2.5 could arise liver apoptosis (the reduced levels of Bcl-2 and the elevated levels of BAX). Our findings were illustrated clearly in [Figure 7], which might explain the negative effect of PM2.5 on NAFLD. | Figure 7: A schematic diagram depicting NAFLD induced by PM2.5 exposure. PM2.5 exposure could induce inflammation (IL-17 and TNF-α), increase liver oxidative stress (the reduced expression of SOD and the elevated expression of MDA), arise liver apoptosis (the reduced expression of Bcl-2 and the elevated expression of BAX)
Click here to view |
Numerous studies have indicated that inflammation plays an important role in the process of NAFLD as it is an inflammatory disease.[29],[30] In addition, studies have illustrated that abnormal upregulation of inflammation caused by stimulants could aggravate hepatic dyslipidemia and lipid accumulation, ultimately promoting the development of NAFLD.[19] In light of this, we assessed the indicators of inflammation to determine their relationship in mice whose PM2.5 exposure increased their risk of NAFLD. We confirmed that the inflammatory factors (IL-17 and TNF-α) in the liver observably increased after PM2.5 exposure for 8 weeks, indicating that long-term PM2.5 exposure might induce hepatic inflammation to aggravate chronic liver injury.
Studies have indicated that oxidative stress, including reactive oxygen species, SOD, and MDA, play important roles in the development of NAFLD.[31],[32],[33] Previous studies have illustrated that abnormal upregulation of oxidative stress can promote the development of NAFLD.[21] Hence, we assessed the indicators of oxidative stress to determine their relationship in mice whose PM2.5 exposure increased their risk of NAFLD. In our study, we found that PM2.5 exposure for 8 weeks decreased SOD level and increased MDA content, which suggested that hepatic oxidative stress induced by long-term PM2.5 exposure might be related to the progress of NAFLD.
Studies have indicated that activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD.[20] Apoptosis is a major process of diseases and is regulated by the pro- and anti-apoptotic proteins of the Bcl-2 family including Bcl-2 and BAX.[34] Upregulation of Bcl-2, as well as a decrease in BAX/Bcl-2 ratios, appears to play a key role in NAFLD. Apoptotic hepatocytes can appeal hepatic stellate cells and immunocytes to the area of fibrosis in the liver by producing inflammasomes and cytokines.[20] In light of this, we assessed the indicators of apoptosis to determine their relationship in mice whose PM2.5 exposure increased their risk of NAFLD. We found that PM2.5 exposure for 8 weeks decreased Bcl-2 level and increased BAX level, which indicated that hepatic apoptosis induced by long-term PM2.5 exposure might aggravate chronic liver injury.
In summary, our data indicated that long-term PM2.5 exposure might aggravate NAFLD through the possible mechanisms of inflammation, oxidative stress, and apoptosis.
Acknowledgment
This work was supported by the Science and Technology Plan of Beijing Tongzhou District (KJ2018CX006).
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Ostro B, Spadaro JV, Gumy S, Mudu P, Awe Y, Forastiere F, et al. Assessing the recent estimates of the global burden of disease for ambient air pollution: Methodological changes and implications for low- and middle-income countries. Environ Res 2018;166:713-25.  |
| 2. | Ustulin M, Park SY, Chin SO, Chon S, Woo JT, Rhee SY. Air pollution has a significant negative impact on intentional efforts to lose weight: A Global scale analysis. Diabetes Metab J 2018;42:320-9. |
| 3. | McGuinn LA, Schneider A, McGarrah RW, Ward-Caviness C, Neas LM, Di Q, et al. Association of long-term PM 2.5 exposure with traditional and novel lipid measures related to cardiovascular disease risk. Environ Int 2019;122:193-200. |
| 4. | Chen C, Zhu P, Lan L, Zhou L, Liu R, Sun Q, et al. Short-term exposures to PM 2.5 and cause-specific mortality of cardiovascular health in China. Environ Res 2018;161:188-94. |
| 5. | Gutiérrez-Avila I, Rojas-Bracho L, Riojas-Rodríguez H, Kloog I, Just AC, Rothenberg SJ. Cardiovascular and cerebrovascular mortality associated with acute exposure to PM 2.5 in Mexico city. Stroke 2018;49:1734-6. |
| 6. | Lin X, Liao Y, Hao Y. The burden of cardio-cerebrovascular disease and lung cancer attributable to PM 2.5 for 2009, Guangzhou: A retrospective population-based study. Int J Environ Health Res 2019;29:1-11. |
| 7. | Liu C, Xu X, Bai Y, Zhong J, Wang A, Sun L, et al. Particulate air pollution mediated effects on insulin resistance in mice are independent of CCR2. Part Fibre Toxicol 2017;14:6. |
| 8. | Chen T, Zhang J, Zeng H, Zhang Y, Zhang Y, Zhou X, et al. The impact of inflammation and cytokine expression of PM 2.5 in AML. Oncol Lett 2018;16:2732-40. |
| 9. | Ge CX, Qin YT, Lou DS, Li Q, Li YY, Wang ZM, et al. IRhom2 deficiency relieves TNF-α associated hepatic dyslipidemia in long-term PM 2.5-exposed mice. Biochem Biophys Res Commun 2017;493:1402-9. |
| 10. | Kowalska M, Kocot K. Short-term exposure to ambient fine particulate matter (PM2,5 and PM10) and the risk of heart rhythm abnormalities and stroke. Postepy Hig Med Dosw (Online) 2016;70:1017-25. |
| 11. | Zhang Q, Li Q, Ma J, Zhao Y. PM 2.5 impairs neurobehavior by oxidative stress and myelin sheaths injury of brain in the rat. Environ Pollut 2018;242:994-1001. |
| 12. | Patel SS, Siddiqui MS. Current and emerging therapies for non-alcoholic fatty liver disease. Drugs 2019;79:75-84. |
| 13. | Braillon A. Non-alcoholic fatty liver disease and disease mongering. Am J Med 2019;11:pii: S0002-9343(19)30042-7. |
| 14. | Rinella ME. Nonalcoholic fatty liver disease: A systematic review. JAMA 2015;313:2263-73. |
| 15. | Byrne CD, Targher G. NAFLD: A multisystem disease. J Hepatol 2015;62:S47-64. |
| 16. | Brunt EM, Wong VW, Nobili V, Day CP, Sookoian S, Maher JJ, et al. Nonalcoholic fatty liver disease. Nat Rev Dis Primers 2015;1:15080. |
| 17. | Zheng Z, Zhang X, Wang J, Dandekar A, Kim H, Qiu Y, et al. Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models. J Hepatol 2015;63:1397-404. |
| 18. | Ge CX, Yu R, Xu MX, Li PQ, Fan CY, Li JM, et al. Betaine prevented fructose-induced NAFLD by regulating LXRα/PPARα pathway and alleviating ER stress in rats. Eur J Pharmacol 2016;770:154-64. |
| 19. | Pirozzi C, Lama A, Simeoli R, Paciello O, Pagano TB, Mollica MP, et al. Hydroxytyrosol prevents metabolic impairment reducing hepatic inflammation and restoring duodenal integrity in a rat model of NAFLD. J Nutr Biochem 2016;30:108-15. |
| 20. | Kanda T, Matsuoka S, Yamazaki M, Shibata T, Nirei K, Takahashi H, et al. Apoptosis and non-alcoholic fatty liver diseases. World J Gastroenterol 2018;24:2661-72. |
| 21. | Apostolopoulou M, Gordillo R, Koliaki C, Gancheva S, Jelenik T, De Filippo E, et al. Specific hepatic sphingolipids relate to insulin resistance, oxidative stress, and inflammation in nonalcoholic steatohepatitis. Diabetes Care 2018;41:1235-43. |
| 22. | Tarantino G, Capone D, Finelli C. Exposure to ambient air particulate matter and non-alcoholic fatty liver disease. World J Gastroenterol 2013;19:3951-6. |
| 23. | Xu MX, Ge CX, Qin YT, Gu TT, Lou DS, Li Q, et al. Prolonged PM 2.5 exposure elevates risk of oxidative stress-driven nonalcoholic fatty liver disease by triggering increase of dyslipidemia. Free Radic Biol Med 2019;130:542-56. |
| 24. | Zhou Y, Zheng T, Chen H, Li Y, Huang H, Chen W, et al. Microbial intervention as a novel target in treatment of non-alcoholic fatty liver disease progression. Cell Physiol Biochem 2018;51:2123-35. |
| 25. | Wan G, Rajagopalan S, Sun Q, Zhang K. Real-world exposure of airborne particulate matter triggers oxidative stress in an animal model. Int J Physiol Pathophysiol Pharmacol 2010;2:64-8. |
| 26. | Li F, Yang Z, Stone C, Ding JY, Previch L, Shen J, et al. Phenothiazines enhance the hypothermic preservation of liver grafts: A pilot in vitro study. Cell Transplant 2019;28:318-27. |
| 27. | Zheng Y, Qu J, Xue F, Zheng Y, Yang B, Chang Y, et al. Novel DNA aptamers for parkinson's disease treatment inhibit α-synuclein aggregation and facilitate its degradation. Mol Ther Nucleic Acids 2018;11:228-42. |
| 28. | Qu J, Yan H, Zheng Y, Xue F, Zheng Y, Fang H, et al. The molecular mechanism of alpha-synuclein dependent regulation of protein phosphatase 2A activity. Cell Physiol Biochem 2018;47:2613-25. |
| 29. | Chen Y, Varghese Z, Ruan XZ. The molecular pathogenic role of inflammatory stress in dysregulation of lipid homeostasis and hepatic steatosis. Genes Dis 2014;1:106-12. |
| 30. | Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012;482:179-85. |
| 31. | Fujii J, Homma T, Kobayashi S, Seo HG. Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease. World J Biol Chem 2018;9:1-5. |
| 32. | Ashraf NU, Sheikh TA. Endoplasmic reticulum stress and oxidative stress in the pathogenesis of non-alcoholic fatty liver disease. Free Radic Res 2015;49:1405-18. |
| 33. | Ore A, Akinloye OA. Oxidative stress and antioxidant biomarkers in clinical and experimental models of non-alcoholic fatty liver disease. Medicina (Kaunas) 2019;55. pii: E26. |
| 34. | Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol 2007;35:495-516. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1]
| This article has been cited by | | 1 |
Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice |
|
| Hermes Reyes-Caballero,Xiaoquan Rao,Qiushi Sun,Marc O. Warmoes,Lin Penghui,Tom E. Sussan,Bongsoo Park,Teresa W.-M. Fan,Andrei Maiseyeu,Sanjay Rajagopalan,Geoffrey D. Girnun,Shyam Biswal | | Scientific Reports. 2019; 9(1) | | [Pubmed] | [DOI] | |
|
 |
|
|
|
![[JOURNAL_FULL_NAME]](images/logo.gif){kind=logo}
Search Pubmed for