Abstract
Ephedra sinica (ES) is a promising medicinal plant with a wide range of pharmacological aspects, including antioxidant and anti-inflammatory properties. Fipronil (FN) is a popularly used systemic insecticide in agriculture and veterinary applications. FN exposure can result in a variety of negative health consequences. The study aimed to explore the prophylactic effects of Ephedra sinica extract (ESE) against hepatotoxicity in FN-treated rats by following the TLR4/ MyD88/ NF-κB pathway. ESE was tested for polyphenolic and antioxidant activity. Forty rats were separated into four groups and given orally by FN (10 mg/kg B.W.) and/or ESE (150 mg/kg B.W.). Blood and tissue samples were collected at the end of the experiment and prepared for pathophysiological, gene expression, and pathological analysis. ESE showed strong antioxidant activity, as well as reduced levels of hepatic MDA and oxidative stress markers (H2O2, NO). Hepatic SOD and CAT activities were increased even further. Furthermore, in FN-treated rats, ESE improved liver functions (ALT, AST, ALP, and LDH) and recovered the lipid profile (Cho, TriG, HDL, and LDL). Moreover, by inhibiting TLR4/ MyD88/ NF-κB induction, ESE alleviated hepatic pathological changes and decreased FN-induced elevations of TNF-α, IL-6, and IL-1β mRNA/protein levels. These findings suggested that ESE mitigated FN-induced hepatotoxicity via combating oxidative stress and relieving inflammation.
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Abbreviations
- ALP:
-
alkaline phosphatase
- ALT:
-
alanine aminotransferase
- ANOVA:
-
analysis of variance
- AST:
-
aspartate aminotransferase
- B.W.:
-
body weight
- CAT:
-
catalase
- CCL4 :
-
carbon tetrachloride
- cDNA:
-
complementary deoxyribonucleic acid
- Cho:
-
cholesterol
- Co.:
-
company
- DNA:
-
deoxyribonucleic acid
- DPPH:
-
2,2-diphenyl-1-picrylhydrazyl
- ELISA:
-
enzyme-linked immunosorbent assay
- ES:
-
ephedra sinica
- ESE:
-
ephedra sinica extract
- et al:
-
et alia/ and others
- Fig.:
-
figure
- FN:
-
fipronil
- g:
-
gram
- GAPDH:
-
glyceraldehyde 3-phosphate dehydrogenase
- H2O2 :
-
hydrogen peroxide
- HDL:
-
high-density lipoprotein
- HPLC:
-
high-performance liquid chromatography
- IL-1β :
-
interleukin 1 beta
- IL-6:
-
interleukin 6
- iNOS:
-
inducible nitric oxide
- IκB:
-
inhibitor of nuclear factor kappa-B (IκB)
- Kg :
-
kilogram
- LD50 :
-
lethal dose 50
- LDH:
-
lactate dehydrogenase
- LDL:
-
low-density lipoprotein
- MAP kinase :
-
mitogen-activated protein (MAP) kinase p38
- MAPK:
-
mitogen-activated protein kinase
- MDA:
-
malonadelhyde
- mg:
-
milligram
- mRNA:
-
messenger ribonucleic acid
- MyD88:
-
myeloid differentiation factor 88
- NF-κB:
-
nuclear factor kappa-light-chain-enhancer of activated B cells
- NO:
-
nitric oxide
- No:
-
number
- °C:
-
the degree celsius
- qRT-PCR:
-
quantitative real-time polymerase chain reaction
- RNS:
-
reactive nitrogen species
- ROS:
-
reactive oxygen species
- SD:
-
standard deviation
- SOD:
-
superoxide dismutase
- SPSS:
-
Statistical Package for the Social Sciences
- TLR4:
-
toll-like receptor-4
- TLRs:
-
Toll-like receptors
- TNF-α:
-
tumor necrosis factor alpha
- TriG:
-
triglycerides
- USA:
-
United States of America
- ΔΔCt:
-
2ˆ(–delta delta cycle threshold)
- %:
-
percent sign
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Acknowledgements
The authors acknowledge the financial support of Taif University Researchers Supporting Project number (TURSP-2020/82), Taif University, Taif, Saudi Arabia. The authors would like to thank the Deanship of Scientific Research at King Khalid University, Abha, KSA for funding this work under Grant number (R.G.P.2/122/42).
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Mohamed Seif: conceptualization, methodology, investigation, formal analysis Software, writing—original draft preparation, and, review and editing. Mohamed Deabes: methodology. Ahmad El-Askary: formal analysis. Attalla F. El-Kott: investigation. Ghadeer M. Albadrani: investigation. Amr Seif: methodology and investigation. Zaizhao Wang: review and editing.
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The experimental path and animal handling were carried out under the experiments guidelines approved by the Committee of Animal Ethics in the National Research Centre, Dokki, Cairo, Egypt (No: 1494052021). This ensures the suitable efforts to use the minimum number of animals and reduces their suffering.
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Seif, M., Deabes, M., El-Askary, A. et al. Ephedra sinica mitigates hepatic oxidative stress and inflammation via suppressing the TLR4/MyD88/NF-κB pathway in fipronil-treated rats. Environ Sci Pollut Res 28, 62943–62958 (2021). https://doi.org/10.1007/s11356-021-15142-4
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DOI: https://doi.org/10.1007/s11356-021-15142-4