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Suppression of LPS-Induced Hepato- and Cardiotoxic Effects by Pulicaria petiolaris via NF-κB Dependent Mechanism

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Abstract

Recently, there is an increasing interest in searching for harmless natural products isolated from plant materials that can be used as beneficial dietary supplements and/or therapeutic drug candidates. The present study aimed to test the potential protective role of Pulicaria petiolaris (PP, Asteraceae) against hepatic and cardiotoxic effects associated with lipopolysaccharide (LPS) injection. PP was given orally for 5 days at two different doses before LPS injection. Results have shown that LPS induced remarkable hepatic and cardiac injurious effects in mice. Hepatic damage was evident through increased serum transaminases, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and activity. Estimation of high levels of serum creatine kinase-MB (CK-MB) and cardiac troponin I indicated cardiac damage. Histopathological examination of liver and heart confirmed the biochemical results. Increase in oxidative stress along with a depressed antioxidant status of liver and heart were observed in LPS-intoxicated animals. Furthermore, LPS induced activation of nuclear factor-κB (NF-κB) and subsequent elevation of inflammatory cytokines (TNF-α, IL-6). On the other hand, PP treatment successfully safeguards both organs against LPS-induced injury as indicated by the improvement of the biochemical and histopathological parameters. These results suggest that PP ameliorates LPS-induced hepatic and cardiac oxidative injurious effects via antioxidant and anti-inflammatory effects.

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Abbreviations

ALP:

Alkaline phosphatase

ALT:

Alanine transaminase

AST:

Aspartate aminotransferase

CMC:

Carboxymethylcellulose

CK-MB:

Creatine kinase-MB

cTnI:

Troponin I

DMSO:

Dimethyl sulfoxide

DNA:

Deoxyribonucleic acid

GSSG:

Disulfide compound

GSH:

Reduced glutathione

H2O2 :

Hydrogen peroxide

IHC:

Immunohistochemical

iNOS:

Inducible nitric oxide synthase

LDH:

Lactate dehydrogenase

IL-1, IL-6, IL-8, and IL-12:

Interleukins 1, 6, 8, and 12

LPS:

Lipopolysaccharide

MDA:

Malondialdehyde

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

NF-κB:

Nuclear factor-κB

NO2/NO3 :

Nitrite/nitrate

SOD:

Superoxide dismutase

TNF-α:

Tumor necrosis factor-α

PP:

Pulicaria petiolaris

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Acknowledgements

The authors acknowledge the Deanship of Scientific Research (DSR), Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia, for assistance.

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Contributions

GAM and SRMI were responsible for the collection of the plant and preparation of the extract. DSE, NA, GAM, HA, and SRMI conceived and designed the research. DSE, NA, HA and ME conducted the experiments and analyzed data. DSE, GAM, HA, and SRMI wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Sabrin Ragab Mohamed Ibrahim.

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Ahmed, N., El-Agamy, D.S., Mohammed, G.A. et al. Suppression of LPS-Induced Hepato- and Cardiotoxic Effects by Pulicaria petiolaris via NF-κB Dependent Mechanism. Cardiovasc Toxicol 20, 121–129 (2020). https://doi.org/10.1007/s12012-019-09539-4

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