Hydroxychloroquine Mitigates Cytokine Storm and Prevents Critical Illness Neuromyopathy in a Rat Sepsis Model

<i>Background and Objectives:</i> It is known that critical illness and associated neuromuscular problems begin to appear in patients hospitalized in the intensive care unit (ICU) for more than a week. The goal of this study was to research the role of hydroxychloroquine (HCQ) in the tre...

Full description

Saved in:
Bibliographic Details
Main Authors: Elif Eygi, Onur Kucuk, Semih Aydemir, Merve Atilgan, Recep Dokuyucu, Oytun Erbas
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Medicina
Subjects:
Online Access:https://www.mdpi.com/1648-9144/60/11/1791
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850226762528587776
author Elif Eygi
Onur Kucuk
Semih Aydemir
Merve Atilgan
Recep Dokuyucu
Oytun Erbas
author_facet Elif Eygi
Onur Kucuk
Semih Aydemir
Merve Atilgan
Recep Dokuyucu
Oytun Erbas
author_sort Elif Eygi
collection DOAJ
description <i>Background and Objectives:</i> It is known that critical illness and associated neuromuscular problems begin to appear in patients hospitalized in the intensive care unit (ICU) for more than a week. The goal of this study was to research the role of hydroxychloroquine (HCQ) in the treatment of cytokine storm and critical illness neuromyopathy (CINM) in a rat sepsis model. <i>Materials and Methods:</i> Rats were assigned into three groups, and a feces intraperitoneal-injection group (FIP) procedure was carried out on 30 rats to induce a model of sepsis for critical illness polyneuromyopathy (CINM). The study groups were as follows: Group 1: control (nonoperative and orally fed control, <i>n</i> = 10), Group 2: FIP with 0.9% NaCl saline was given as 1 mL/kg/day by oral gavage (<i>n</i> = 10), and Group 3: FIP with 10 mg/kg/day of hydroxychloroquine (Plaquenil 200 mg) administered by oral gavage (<i>n</i> = 10). Electrophysiological recordings (EMG) were conducted six days after surgery. EMG was carried out three times on the right sciatic nerve, which was stimulated with supramaximal intensity utilizing a bipolar needle electrode at the sciatic notch. Tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), lactic acid levels, and interleukin-6 (IL-6) were evaluated. <i>Results:</i> In terms of TNF-α, MDA, lactic acid levels, and IL-6, there was a statistically significant decrease in the CINM + 10 mg/kg HCQ group compared to the CINM and saline group (<i>p</i> < 0.0001, <i>p</i> < 0.05, <i>p</i> < 0.05, and <i>p</i> < 0.05, respectively). Compound muscle action potentials (CMAPs) latency and duration were decreased in the CINM + 10 mg/kg HCQ group compared to other groups (<i>p</i> < 0.01 and <i>p</i> < 0.001). However, CMAP amplitude was significantly higher in the CINM + 10 mg/kg HCQ group unlike the CINM and saline group (<i>p</i> < 0.001). <i>Conclusions:</i> This is the first study to demonstrate the effects of HCQ on CINM in a rat model of sepsis. The findings of our research suggest that hydroxychloroquine may be used as a potential therapeutic agent in the treatment of sepsis. Hydroxychloroquine may have an important effect in the pathogenesis of sepsis-associated CINM by reducing cytokine production and oxidative stress.
format Article
id doaj-art-5ae22b26823540b8a767bd9b90fb0cd7
institution OA Journals
issn 1010-660X
1648-9144
language English
publishDate 2024-11-01
publisher MDPI AG
record_format Article
series Medicina
spelling doaj-art-5ae22b26823540b8a767bd9b90fb0cd72025-08-20T02:04:59ZengMDPI AGMedicina1010-660X1648-91442024-11-016011179110.3390/medicina60111791Hydroxychloroquine Mitigates Cytokine Storm and Prevents Critical Illness Neuromyopathy in a Rat Sepsis ModelElif Eygi0Onur Kucuk1Semih Aydemir2Merve Atilgan3Recep Dokuyucu4Oytun Erbas5Department of Anesthesiology and Reanimation, Gaziantep City Training and Research Hospital, Gaziantep 27470, TurkeyDepartment of Anesthesiology and Reanimation, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara 06000, TurkeyDepartment of Anesthesiology and Reanimation, Yenimahalle Training and Research Hospital, University of Yıldırım Beyazit, Ankara 06370, TurkeyDepartment of Pediatric Surgery, School of Medicine, Necmettin Erbakan University, Konya 42140, TurkeyDepartment of Physiology, Medical Specialization Training Center (TUSMER), Ankara 06230, TurkeyDepartment of Physiology, School of Medicine, Demiroglu Bilim University, Istanbul 34570, Turkey<i>Background and Objectives:</i> It is known that critical illness and associated neuromuscular problems begin to appear in patients hospitalized in the intensive care unit (ICU) for more than a week. The goal of this study was to research the role of hydroxychloroquine (HCQ) in the treatment of cytokine storm and critical illness neuromyopathy (CINM) in a rat sepsis model. <i>Materials and Methods:</i> Rats were assigned into three groups, and a feces intraperitoneal-injection group (FIP) procedure was carried out on 30 rats to induce a model of sepsis for critical illness polyneuromyopathy (CINM). The study groups were as follows: Group 1: control (nonoperative and orally fed control, <i>n</i> = 10), Group 2: FIP with 0.9% NaCl saline was given as 1 mL/kg/day by oral gavage (<i>n</i> = 10), and Group 3: FIP with 10 mg/kg/day of hydroxychloroquine (Plaquenil 200 mg) administered by oral gavage (<i>n</i> = 10). Electrophysiological recordings (EMG) were conducted six days after surgery. EMG was carried out three times on the right sciatic nerve, which was stimulated with supramaximal intensity utilizing a bipolar needle electrode at the sciatic notch. Tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), lactic acid levels, and interleukin-6 (IL-6) were evaluated. <i>Results:</i> In terms of TNF-α, MDA, lactic acid levels, and IL-6, there was a statistically significant decrease in the CINM + 10 mg/kg HCQ group compared to the CINM and saline group (<i>p</i> < 0.0001, <i>p</i> < 0.05, <i>p</i> < 0.05, and <i>p</i> < 0.05, respectively). Compound muscle action potentials (CMAPs) latency and duration were decreased in the CINM + 10 mg/kg HCQ group compared to other groups (<i>p</i> < 0.01 and <i>p</i> < 0.001). However, CMAP amplitude was significantly higher in the CINM + 10 mg/kg HCQ group unlike the CINM and saline group (<i>p</i> < 0.001). <i>Conclusions:</i> This is the first study to demonstrate the effects of HCQ on CINM in a rat model of sepsis. The findings of our research suggest that hydroxychloroquine may be used as a potential therapeutic agent in the treatment of sepsis. Hydroxychloroquine may have an important effect in the pathogenesis of sepsis-associated CINM by reducing cytokine production and oxidative stress.https://www.mdpi.com/1648-9144/60/11/1791critical illness neuromyopathyhydroxychloroquineinterleukin-6malondialdehydetumor necrosis factor-alphamuscle action potential
spellingShingle Elif Eygi
Onur Kucuk
Semih Aydemir
Merve Atilgan
Recep Dokuyucu
Oytun Erbas
Hydroxychloroquine Mitigates Cytokine Storm and Prevents Critical Illness Neuromyopathy in a Rat Sepsis Model
Medicina
critical illness neuromyopathy
hydroxychloroquine
interleukin-6
malondialdehyde
tumor necrosis factor-alpha
muscle action potential
title Hydroxychloroquine Mitigates Cytokine Storm and Prevents Critical Illness Neuromyopathy in a Rat Sepsis Model
title_full Hydroxychloroquine Mitigates Cytokine Storm and Prevents Critical Illness Neuromyopathy in a Rat Sepsis Model
title_fullStr Hydroxychloroquine Mitigates Cytokine Storm and Prevents Critical Illness Neuromyopathy in a Rat Sepsis Model
title_full_unstemmed Hydroxychloroquine Mitigates Cytokine Storm and Prevents Critical Illness Neuromyopathy in a Rat Sepsis Model
title_short Hydroxychloroquine Mitigates Cytokine Storm and Prevents Critical Illness Neuromyopathy in a Rat Sepsis Model
title_sort hydroxychloroquine mitigates cytokine storm and prevents critical illness neuromyopathy in a rat sepsis model
topic critical illness neuromyopathy
hydroxychloroquine
interleukin-6
malondialdehyde
tumor necrosis factor-alpha
muscle action potential
url https://www.mdpi.com/1648-9144/60/11/1791
work_keys_str_mv AT elifeygi hydroxychloroquinemitigatescytokinestormandpreventscriticalillnessneuromyopathyinaratsepsismodel
AT onurkucuk hydroxychloroquinemitigatescytokinestormandpreventscriticalillnessneuromyopathyinaratsepsismodel
AT semihaydemir hydroxychloroquinemitigatescytokinestormandpreventscriticalillnessneuromyopathyinaratsepsismodel
AT merveatilgan hydroxychloroquinemitigatescytokinestormandpreventscriticalillnessneuromyopathyinaratsepsismodel
AT recepdokuyucu hydroxychloroquinemitigatescytokinestormandpreventscriticalillnessneuromyopathyinaratsepsismodel
AT oytunerbas hydroxychloroquinemitigatescytokinestormandpreventscriticalillnessneuromyopathyinaratsepsismodel