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Mechanistic insight on the role of leukotriene receptors in ischemic–reperfusion injury

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Abstract

Leukotrienes (LT) are a class of inflammatory mediators produced by the 5-lipoxygenase (5-LO) enzyme from arachidonic acid (AA). We discussed the various LT inhibitors and downstream pathway modulators, such as Mitogen-Activated Protein Kinases (MAPK), Phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/Akt), 5′-Adenosine Monophosphate-Activated Protein Kinase (AMPK), Protein Kinase C (PKC), Nitric Oxide (NO), Bradykinin, Early Growth Response-1 (Egr-1), Nuclear Factor-κB (NF-κB), and Tumor Necrosis Factor-Alpha (TNF-α), which in turn regulate various metabolic and physiological processes involving I/R injury. A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to understand the nature and mechanistic interventions of the leukotriene receptor modulations in ischemic injury. In the pathophysiology of I/R injuries, LT has been found to play an important role. I/R injury affects most of the vital organs and is characterized by inflammation, oxidative stress, cell death, and apoptosis leading to morbidity and mortality. sThis present review focuses on the various LT receptors, i.e., CysLT, LTC4, LTD4, and LTE4, involved in developing I/R injury in organs, such as the brain, spinal cord, heart, kidney, liver, and intestine.

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Abbreviations

5- LO/LOX:

5-Lipoxygenase

AA:

Arachidonic acid

AST:

Aspartate aminotransferase

AMPK:

5′-Adenosine monophosphate-activated protein kinase

ARF:

Acute renal failure

ASM:

Airway smooth muscle

BBB:

Blood–brain barrier

BLT1:

Leukotriene B4 receptors

Ca2 + :

Calcium ion

cPLA2:

Cytosolic phospholipase A2

CysLTs:

Cysteinyl leukotrienes

ERK:

Extracellular signal-related kinases

FLAP:

5-Lipoxygenase activating protein

GPCR:

G protein-coupled receptor

GPR 17:

G protein-coupled receptor 17

GSH:

Reduced glutathione

GTP:

Guanosine -5′-triphosphate

HETEs:

Hydroxyeicosotetraenoic acids

HPETE:

Hydroperoxyeicosatetraenoic acid

I/R:

Ischemic reperfusion

IRI:

Ischemic reperfusion injury

JNK:

Jun amino-terminal kinases

Kae:

Kaempferide

LT:

Leukotrienes

LTA4:

Leukotriene A4

LTB4:

Leukotriene B4

LTC4:

Leukotriene C4

LTC4S:

Leukotriene C4 synthase

LTD4:

Leukotriene D4

LTE4:

Leukotriene E4

LV:

Left ventricular

LXA4:

Lipoxin A4

MAPK:

Mitogen-activated protein kinases

MCAO:

Middle cerebral artery occlusion

MEK–ERK:

Mitogen-activated protein kinase–extracellular signal-related kinase

MGST:

Microsomal glutathione-S-transferase

MPO:

Myeloperoxidase

NaB:

Sodium butyrate

OGD:

Oxygen–glucose deprivation

OPCs:

Oligodendrocyte precursor cells

PI3K:

Phosphatidylinositol 3-Kinase

PKB:

Protein kinase B

PLA2:

Phospholipase A2

PMNL:

Polymorphonuclear leukocytes

ROS:

Reactive oxygen species

Sal A:

Salvianolic acid A

TNF-α:

Tumor necrosis factor-alpha

TXA2:

Thromboxane A2

UDP:

Uridine diphosphate

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Acknowledgements

The present study received no funding from any source or any governing body. The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India, for providing the necessary facilities.

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  1. Chitkara College of Pharmacy, Chitkara University, Punjab, India

    Heena Khan, Anjali Gupta, Thakur Gurjeet Singh & Amarjot Kaur

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Conceptualization: Conceived and designed the experiments: Thakur Gurjeet Singh. Analyzed the data: Heena Khan, Anjali Gupta. Wrote the manuscript: Heena Khan, Anjali Gupta Editing of the Manuscript: Amarjot Kaur Grewal Critically reviewed the article: Dr. Thakur Gurjeet Singh. All authors read and approved the final manuscript.

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Khan, H., Gupta, A., Singh, T.G. et al. Mechanistic insight on the role of leukotriene receptors in ischemic–reperfusion injury. Pharmacol. Rep 73, 1240–1254 (2021). https://doi.org/10.1007/s43440-021-00258-8

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