Abstract
The purpose of this study was to explore the interventional effects of folic acid on the heart damage caused by lead acetate exposure. Twenty-four 60-day-old male Sprague–Dawley (SD) rats were randomly divided into 4 groups with 6 rats in each group. The control group (C group) was normal rats; the lead exposure group (L group) rats drank 0.2% lead acetate solution freely for 14 days. The rats in the intervention group (T group) were given 0.2% lead acetate solution for 14 days, respectively, and 0.4 mg/kg BW folic acid solution was given to the rats by gavage on the 7th day of lead administration. The rats in the folic acid group (group E) were given 0.4 mg/kg BW folic acid solution by gavage. To weigh rat body weight and heart weight, calculate heart index, and observe the expression level of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase 1(HO-1), glucose-regulated protein 78/binding immunoglobulin protein (GRP78), and C/EBP-homologous protein (CHOP) by immunofluorescence method. The results showed that compared with group C, serum lead levels in group L and T were significantly increased (P < 0.05); superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX) levels in group L were significantly decreased (P < 0.05), and malondialdehyde (MDA) content was significantly higher increased (P < 0.05), and the GSH-PX content in group T were significantly increased in group L (P < 0.05), and the MDA content in group T was significantly lower than that in group L (P < 0.05). Compared with group C, the expression of Nrf2, HO-1, GRP78, and CHOP in group L increased significantly, and the difference was statistically significant (P < 0.05). Compared with the L group, the expression of Nrf2, HO-1, GRP78, and CHOP in the T group was reduced. Therefore, folic acid has a certain protective effect on the oxidative damage of lead-exposed rat heart tissue.
Graphical abstract
Lead exposure will increase ROS, NO, MDA, and other oxidizing substances and reduce the level of GSH, SOD, CAT, GPx, and other antioxidant factors, which will lead to cardiac hypertrophy, cardiac index increase, oxidative stress, Nrf2, and HO-1. The expression of stress-related proteins such as GRP78 and CHOP also increased, leading to cardiomyocyte apoptosis. After a folic acid intervention, these changes can be significantly reversed.
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Data availability
All data generated during this study are available from the corresponding author on request.
Abbreviations
- ROS:
-
Reactive oxygen species
- Nrf2:
-
Nuclear factor erythroid 2-related factor 2
- HO-1:
-
Heme oxygenase 1
- ERS:
-
Endoplasmic reticulum stress
- GRP78:
-
Glucose-regulated protein 78/binding immunoglobulin protein
- ER:
-
Endoplasmic reticulum
- CHOP:
-
C/EBP-homologous protein
- NO:
-
Nitric oxide
- NOS:
-
Nitric oxide synthase
- GSH:
-
Glutathione
- GSH-PX:
-
Glutathione peroxidase
- GSR:
-
Glutathione reductase
- SOD:
-
Superoxide dismutase
- MDA:
-
Malondialdehyde
- DOXO:
-
Doxorubicin
- TNF-α:
-
Tumor necrosis factor-α
- CO2 :
-
Carbon dioxide
- SSA:
-
Specific surface area
- Keap1:
-
Kelch-like erythrocyte-derived protein 1;
- ERK1/2:
-
Extracellular signal-regulated kinase
- AKT:
-
Phosphoinositide3-kinase(PI3K)/protein kinase B
- P38:
-
Protein kinase
- JNK:
-
C-Jun NH2-terminal kinase
- CO:
-
Carbon monoxide
- Hhcy:
-
Hyperhomocysteinemia
- RON:
-
Reactive nitrogen
- Hcy:
-
Homocysteine
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Acknowledgements
The author thanks all co-authors in the team for participating in this study. Thanks to Dr. Ning Li and Dr. Fangyu Wang. Thanks to the School of Food Science and Technology of Henan Agricultural University and the Key Laboratory of Animal Immunology of Henan Academy of Agricultural Sciences for their great assistance.
Funding
This research was supported by the National Natural Science Foundation of China (NNSFC) by grant NNSFC – 31201878, U1204804, and U1604183. It has also been funded by the Excellent Youth Project of the Natural Science Foundation of Henan Province (202300410193), Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control (20171215) and 2022 Henan Province Postgraduate Joint Training Base Project (YJS2022JD16).
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Ning Li and Yali Zhao participated in the design of this study, statistical analysis, drafting of manuscripts, and literature search. Fangyu Wang, Lianjun Song, and Mingwu Qiao conducted experimental paper design, knowledge content definition, document retrieval, data collection, data analysis, and manuscript preparation. Tianlin Wang and Xianqing Huang provided assistance in literature retrieval, data collection, and manuscript editing. All authors read and approve the final manuscript.
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All experimental procedures passed the Animal Protection and Utilization Committee of Henan Academy of Agricultural Sciences-in line with the National Institutional Animal Care Guidelines. Try to protect animal welfare and reduce animal suffering (Zhengzhou, China). All co-authors are known and agreed to be published in this journal.
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Li, N., Zhao, Y., Wang, F. et al. Folic acid alleviates lead acetate-mediated cardiotoxicity by down-regulating the expression levels of Nrf2, HO-1, GRP78, and CHOP proteins. Environ Sci Pollut Res 29, 55916–55927 (2022). https://doi.org/10.1007/s11356-022-19821-8
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DOI: https://doi.org/10.1007/s11356-022-19821-8