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Flavonoid-rich fraction attenuates permethrin-induced toxicity by modulating ROS-mediated hepatic oxidative stress and mitochondrial dysfunction ex vivo and in vivo in rat

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Abstract

The present study explores the antioxidant, anti-microbial, and hepatoprotective potentials of flavonoid-rich fractions from Fumaria officinalis against permethrin-induced liver damage ex vivo/in vivo in rat. However, HPLC-DAD analysis revealed the richness of 6 components in ethyl acetate fraction (EAF) where ferulic acid, rosmarinic acid, and myricetin are the most abundant. The in vitro assays showed that EAFs have impressive antioxidant and anti-microbial properties. Ex vivo, permethrin (PER) (100 μM) induced a decrease of hepatic AST and ALT activities and 25-OH vitamin D and vitamin C levels and an increase of ALP and LDH activities, TBARS, and ϒ-GT levels with a disturbance of oxidative status. The hepatoprotective effect of EAF (1 mg/mL) against PER was confirmed by the amelioration of oxidative stress profile. In vivo, permethrin was found to increase absolute and relative liver weights, plasma transaminase activities, lactate-to-pyruvate ratio, hepatic and mitochondrial lipid peroxidation, and protein oxidation levels. This pesticide triggered a decrease of Ca2+ and Mg2+-ATPases and mitochondrial enzyme activities. The co-treatment with EAF reestablished the hepatic and mitochondrial function, which could be attributed to its richness in phenolic compounds.

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Abbreviations

25-OH vitamin D:

25 hydroxy-vitamin D

ABTS:

2,2′-azinobis (3-ethylbenzothiazoline)-6-sulfonique

ALP:

alkaline phosphatase

ALT:

alanine aminotransferase

AOPP:

advanced oxidation protein products

AST:

aspartate aminotransferase

ATP:

adenosine triphosphate

CAT:

catalase

CRP:

C-reactive protein

DNA:

deoxyribonucleic acid

DPPH:

2,2-diphenyl-1-picrylhydrazyle

DW:

dry weight

EAF:

ethyl acetate fraction

FRAP:

ferric reducing power

FT-IR:

Fourier transform infrared spectroscopy

GAE:

gallic acid

GPx:

glutathione peroxidase

GSH:

glutathione

HPLC-DAD:

high-performance liquid chromatography with diode array detection

LDH:

lactate dehydrogenase

NADH:

nicotinamide adenosine dinucleotide

NBF:

N-butanol fraction

NO:

nitrite oxide

NPSH:

non-protein bound

PCO:

protein carbonyl

PER:

permethrin

QE:

quercetin

RNS:

reactive nitrogen species

ROS:

reactive oxygen species

SOD:

superoxide dismutase

TBARS:

thiobarbituric acid reactive substances

TCA:

tricarboxylic acid

Vit C:

vitamin C

WF:

water fraction

ϒ-GT:

gamma-glutamyl transpeptidase

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Acknowledgments

The authors acknowledge the “Ministry of higher Education, Scientific Research and Technology, Tunisia,” for the support of this work.

Funding

The project was funded by the Department of biology in faculty of sciences of Sfax (Tunisia).

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N. Aoiadni: investigation, methodology, formal analysis, writing-review and editing. H. Ayadi: methodology. H. Jdidi: methodology. M. Naifer: methodology. S. Maalej: resources. F.A. Makni: resources. A. El Feki: resources. H. Fetoui: conceptualization, writing-review and editing. F.G. Koubaa: project administration, resources, conceptualization, supervision, writing-review and editing.

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Correspondence to Nissaf Aoiadni.

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Aoiadni, N., Ayadi, H., Jdidi, H. et al. Flavonoid-rich fraction attenuates permethrin-induced toxicity by modulating ROS-mediated hepatic oxidative stress and mitochondrial dysfunction ex vivo and in vivo in rat. Environ Sci Pollut Res 28, 9290–9312 (2021). https://doi.org/10.1007/s11356-020-11250-9

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