Beneficial effects of tannic acid on comorbid anxiety in cecal ligation and puncture-induced sepsis in rats and potential underlying mechanisms.

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 (20mg/kg, i.p.), 6, 12, and 18h 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.