Green propolis extract attenuates acute kidney injury and lung injury in a rat model of sepsis

Marcelo Augusto Duarte Silveira,Roberto De Sousa Moreira,Flávio Teles,Andresa Berretta,Irene L Noronha,Maria Heloisa Shimizu,Talita Rojas Sanches,Lúcia Andrade,José Manuel Condor Capcha,Margot S Garnica

doi:10.1038/s41598-021-85124-6

Marcelo Augusto Duarte Silveira, Roberto De Sousa Moreira + Show 8 more

Open Access

https://doi.org/10.1038/s41598-021-85124-6

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Abstract

Sepsis is the leading cause of acute kidney injury (AKI) and lung injury worldwide. Despite therapeutic advances, sepsis continues to be associated with high mortality. Because Brazilian green propolis (GP) has promising anti-inflammatory, antioxidant, and immunomodulatory properties, we hypothesized that it would protect kidneys and lungs in rats induced to sepsis by cecal ligation and puncture (CLP). Male Wistar rats were divided into groups—control (sham-operated); CLP (CLP only); and CLP + GP (CLP and treatment with GP at 6 h thereafter)—all receiving volume expansion and antibiotic therapy at 6 h after the procedures. By 24 h after the procedures, treatment with GP improved survival, attenuated sepsis-induced AKI, and restored renal tubular function. Whole-blood levels of reduced glutathione were higher in the CLP + GP group. Sepsis upregulated the Toll-like receptor 4/nuclear factor-kappa B axis in lung and renal tissues, as well as increasing inflammatory cytokine levels and macrophage infiltration; all of those effects were attenuated by GP. Treatment with GP decreased the numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells in renal and lung tissue, as well as protecting the morphology of the renal mitochondria. Our data open the prospect for clinical trials of the use of GP in sepsis.

Highlights

Sepsis is the leading cause of acute kidney injury (AKI) and lung injury worldwide
Mortality was significantly lower in the cecal ligation and puncture (CLP) + green propolis (GP) group than in the CLP group
The mean GFR in the CLP + GP group (0.684 ± 0.137 ml/min/100 g body weight (BW)) was higher than that observed for the CLP group (p < 0.05), it did not differ significantly between the control and CLP + GP groups (Fig. 3)

Summary

Introduction

Sepsis is the leading cause of acute kidney injury (AKI) and lung injury worldwide. Despite therapeutic advances, sepsis continues to be associated with high mortality. Sepsis upregulated the Toll-like receptor 4/nuclear factor-kappa B axis in lung and renal tissues, as well as increasing inflammatory cytokine levels and macrophage infiltration; all of those effects were attenuated by GP. Acute kidney injury (AKI) occurs in 20–40% of patients with sepsis treated in the intensive care unit and is often present in those with multiple organ d ysfunction[2,3,4,5], among whom mortality can be as high as 60%4. Toll-like receptors (TLRs), innate immune system effectors that are present in defense cells and in renal proximal tubular cells, recognize damage-associated and pathogen-associated molecular p atterns[5,8] Stimuli such as oxidative stress and TLR4 signaling activate nuclear factor-kappa B (NF-κB), triggering cytokine transcription and release, which result in inflammation[5,7,12]. It contains a number of substances with medicinal properties, having long been used by various populations[15,16]

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