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...

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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
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Online Access:https://www.mdpi.com/1648-9144/60/11/1791
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Summary:<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.
ISSN:1010-660X
1648-9144