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 (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), oxidative stress parameters (MDA and SOD) and protein levels (GABAA receptors and IL-1β) were measured in the brain tissue samples. Administration of tannic acid significantly improved sepsis score and hypotension which 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 brain tissue samples compared to the Sepsis group. This study indicated that tannic acid mitigated anxiety-related behaviors through decreasing inflammation and oxidative stress and positive modifying IL-1β/GABAA receptors pathway. Therefore, tannic acid shows promise as an efficacious treatment for comorbid anxiety in septic patients.