Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2015 May;17(3):711-22.
doi: 10.1208/s12248-014-9714-4. Epub 2015 Mar 12.

Lipidomics revealed idiopathic pulmonary fibrosis-induced hepatic lipid disorders corrected with treatment of baicalin in a murine model

Changfeng Hu  1 , Yiqi Wang, Yongsheng Fan, Haichang Li, Chunyan Wang, Jida Zhang, Shuijuan Zhang, Xianlin Han, Chengping Wen
Affiliations
Comparative Study

Lipidomics revealed idiopathic pulmonary fibrosis-induced hepatic lipid disorders corrected with treatment of baicalin in a murine model

Changfeng Hu et al. AAPS J. 2015 May.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease. The current standard treatment with glucocorticoids (GCs) leads to many adverse effects, and its effectiveness is questionable. Thus, it is critical and urgent to find new drug(s) for treatment of IPF. Baicalin (BAI) is an attractive candidate for this purpose. Herein, utilizing shotgun lipidomics, we revealed that IPF could lead to a lipid disorder of the liver in an animal model induced by bleomycin and confirmed through histopathological studies of the lung. Lipidomics further demonstrated that this disorder could virtually be corrected after treatment with BAI, but not with dexamethasone (DEX) (a commonly used GC for treatment of IPF). In contrast, the treatment with DEX did not improve IPF but led to tremendous alterations in hepatic lipidomes and accumulation of fat in the liver, which was very different from the lipid disorder induced by IPF. The underpinning mechanisms of the IPF-resultant lipid disorder and DEX-induced lipotoxicity as revealed by shotgun lipidomics were extensively discussed. Taken together, the current study showed that IPF could lead to hepatic lipid disorder, which can be treated with BAI, and demonstrated that lipidomics could be a powerful tool for drug screening.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Collagen deposition in the lung of mice induced by BLM with or without treatment as assessed by staining. Lung tissue sections of mice in the control group (a), the BLM-induced model group (b), the BLM-induced model group treated with DEX (c), and the BLM-induced model group treated with BAI (d) were collected on the 26th day post-BLM injection with standard procedures as described in the “MATERIALS AND METHODS” section. H&E staining was visualized by using photomicroscope (Leica DM LB2; Wetzlar, Germany). Each image represents the staining experiments from at least five animals of individual group and was obtained with ×200 magnification from origin. The effects of different treatments on BLM-induced lung fibrosis fraction were assessed quantitatively by quantitative image analysis of Masson’s trichrome staining 26 days post-BLM injection (e). The data represent means ± SD from the individual animals (control, n = 5; model, n = 4; DEX, n = 5; and BAI, n = 4). *P < 0.05 and ***P < 0.001 compared with that of the model group
Fig. 2
Fig. 2
Multivariate analysis of lipidomics data. The PCA score (a) and loading (b) plots were obtained based on the mass levels of individual hepatic lipid species of mice of different groups: control (n = 5), model (n = 4), DEX (n = 5), and BAI (n = 4). The detailed information about the abbreviations of lipid species is given in Table S2
Fig. 3
Fig. 3
Comparison of the amounts of cardiolipin, monolysocardiolipin, and phosphatidylglycerol species present in hepatic lipid extracts from different mouse groups. Liver tissue samples of the control (n = 5, blue), model (n = 4, purple), DEX (n = 5, green), and BAI (n = 4, red) groups were collected and lipid extracts were prepared by using a modified Bligh and Dyer procedure as described in the “MATERIALS AND METHODS” section. The amounts of CL (a), MLCL (b), and phosphatidylglycerol (PG) (c) species were identified and quantified by MDMS-SL as previously described (28). The data represent means ± SD from the separate animals. Only the major species were displayed. *P < 0.05, **P < 0.01, and ***P < 0.001 compared with those in the control group
Fig. 4
Fig. 4
Comparison of the amount of phosphatidylcholine and lysophosphatidylcholine species present in hepatic lipid extracts from different mouse groups. Liver tissue samples of the control (n = 5, blue), model (n = 4, purple), DEX (n = 5, green), and BAI (n = 4, red) groups were collected and lipid extracts were prepared by using a modified Bligh and Dyer procedure as described in the “MATERIALS AND METHODS” section. The abundance of PC (a) or lysoPC (b) species was identified and quantified by MDMS-SL as previously described (28). The data represent means ± SD from the individual animals. Only the major species were displayed. *P < 0.05, **P < 0.01, and ***P < 0.001 compared with those in the control group. The letter “A” stands for alkyl (ether-linked) species
Fig. 5
Fig. 5
Comparison of the peak intensities of phosphatidylinositol species or the amount of phosphatidylserine and phosphatidylethanolamine species present in hepatic lipid extracts from different mouse groups. Liver tissue samples of the control (n = 5, blue), model (n = 4, purple), DEX (n = 5, green), and BAI (n = 4, red) groups were collected and lipid extracts were prepared by using a modified Bligh and Dyer procedure as described in the “MATERIALS AND METHODS” section. The amount of PI (a), PS (b), or PE (c) species was identified and quantified by MDMS-SL as previously described (28). The data represent means ± SD from the individual animals. Only the major species were displayed. *P < 0.05, **P < 0.01, and ***P < 0.001 compared with those in the control group
Fig. 6
Fig. 6
Comparison of the amount of ceramide and sphingomyelin species present in hepatic lipid extracts from different mouse groups. Liver tissue samples of the control (n = 5, blue), model (n = 4, purple), DEX (n = 5, green), and BAI (n = 4, red) groups were collected and lipid extracts were prepared by using a modified Bligh and Dyer procedure as described in the “MATERIALS AND METHODS” section. The amount of ceramide (a) or sphingomyelin (SM) (b) was identified and quantified by MDMS-SL as previously described (28). The data represent means ± SD from the individual animals. Only the major species were displayed. *P < 0.05, **P < 0.01, and ***P < 0.001 compared with those in the control group. “N” stands for the amide linage of the acyl chain
Fig. 7
Fig. 7
Comparison of the abundance and composition of PA, triacylglycerol, and fatty acyls present in triacylglycerol pools of hepatic lipid extracts from different mouse groups. Liver tissue samples of the control (n = 5, blue), model (n = 4, purple), DEX (n = 5, green), and BAI (n = 4, red) groups were collected and lipid extracts were prepared by using a modified Bligh and Dyer procedure as described in the “MATERIALS AND METHODS” section. The abundance of TAG species was identified and quantified by MDMS-SL as previously described (28,58). The data of PA (a) and TAG (b) species represent means ± SD from the individual animals. ***P < 0.001 compared with those in the control group. The amount of individual fatty acyl chain was derived from the amount of the identified and quantified TAG species. The heat maps showed the P values of statistical significance of the amount (c) and composition (d) of individual fatty acyls relative to the counterparts in the control group, respectively. The negative symbol after the P values in the heat maps indicates the reduction of the values in comparison to those in the control group
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Society AT Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS) Am J Respir Crit Care Med. 2000;161:646–64. doi: 10.1164/ajrccm.161.2.ats3-00. - DOI - PubMed
    1. King TE, Jr, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet. 2011;378:1949–61. doi: 10.1016/S0140-6736(11)60052-4. - DOI - PubMed
    1. Ryu JH, Colby TV, Hartman TE. Idiopathic pulmonary fibrosis: current concepts. Mayo Clin Proc. 1998;73:1085–101. doi: 10.4065/73.11.1085. - DOI - PubMed
    1. Ziesche R, Hofbauer E, Wittmann K, Petkov V, Block LH. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 1999;341:1264–9. doi: 10.1056/NEJM199910213411703. - DOI - PubMed
    1. Cooper JA, Jr, White DA, Matthay RA. Drug-induced pulmonary disease. Part 1: cytotoxic drugs. Am Rev Respir Dis. 1986;133:321–40. - PubMed

Publication types