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Beneficial Effects of Tannic Acid on Comorbid Anxiety in Cecal Ligation and Puncture-Induced Sepsis in Rats and Potential Underlying Mechanisms Publisher Pubmed



Ranjbaran M1, 2 ; Kianian F1, 2 ; Ashabi G2 ; Lorian K3 ; Azizi F4
Authors
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Authors Affiliations
  1. 1. Electrophysiology Research Center, Neurosciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, 1417613151, Iran
  3. 3. Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  4. 4. School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran

Source: Naunyn-Schmiedeberg's Archives of Pharmacology Published:2023


Abstract

Sepsis-associated encephalopathy (SAE), a neurological dysfunction caused by sepsis, is the most common complication among septic ICU patients. Given the major role of inflammation in the pathophysiology of sepsis-induced anxiety, an extreme and early manifestation of SAE, the present study examined whether tannic acid, as an anti-inflammatory agent, has anxiolytic effects in cecal ligation and puncture (CLP)-induced sepsis. Forty male Wistar rats were assigned to four groups: (1) sham; (2) sham + tannic acid; (3) sepsis and (4) sepsis + tannic acid. Sepsis was induced by cecal ligation and puncture model. Animals in the sham + tannic acid and sepsis + tannic acid groups received tannic acid (20 mg/kg, i.p.), 6, 12, and 18 h after the sepsis induction. Twenty-four hours after the sepsis induction, systolic blood pressure and sepsis score were assessed. Anxiety-related behaviors were evaluated using elevated plus-maze and dark–light transition tests. Moreover, inflammatory markers (TNF-α and IL-6) and oxidative stress parameters (MDA and SOD) were measured in the brain tissue while protein levels (GABAA receptors and IL-1β) were assessed in the hippocampus. Administration of tannic acid significantly improved sepsis score and hypotension induced by sepsis. Anxiety-related behaviors showed a significant decrease in the sepsis + tannic acid group compared to the sepsis group. Tannic acid caused a significant decrease in the brain inflammatory markers and a remarkable improvement in the brain oxidative status compared to the septic rats. Tannic acid prevented animals from decreasing GABAA receptors and increasing IL-1β protein levels in the hippocampus compared to the sepsis group. This study indicated that tannic acid mitigated anxiety-related behaviors through decreasing inflammation and oxidative stress and positively modifying IL-1β/GABAA receptor pathway. Therefore, tannic acid shows promise as an efficacious treatment for comorbid anxiety in septic patients. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.