Amantadine Enhances IL-10 Expressions to Maintain the Renal Functions Against Inflammation and Oxidative Stress via Increasing PI3K/AKT/HIF-1α Pathway and Decreasing AQP2-4 Signallings.

Abstract

BACKGROUND: This study aimed to show the beneficial effects of amantadine (AMA), used in antiviral medication and Parkinson's therapy, on the inflammatory response and apoptosis in a model of systemic inflammation induced renal damage by lipopolysaccharide (LPS). METHODS: Thirty-two wistar albino rats were divided into four equal groups: control, LPS (5&#x2009;mg/kg), LPS&#x2009;+&#x2009;AMA (45&#x2009;mg/kg) and AMA groups. Both drugs were administered intraperitoneally on the same day with a single dose. The rats were sacrificed 6&#x2009;h after LPS administration. Renal tissues were collected for histopathological, immunohistochemical, biochemical and genetic analyses. RESULTS: Histopathological evaluation revealed a significant increase in all parameters (histological score, hyperemia, hemorrhage, inflammatory infiltration and degeneration/necrosis) in the LPS group compared to the control group (p < 0.05, Kruskal-Wallis test). Dunn's post-hoc analysis showed that AMA treatment (LPS+AMA group) significantly reduced these increases. In the group treated with AMA alone, similar histological integrity was maintained compared to the control group. CONCLUSION: In this study, AMA treatment exhibited anti-inflammatory effects on kidney tissue via several different mechanisms. However, additional studies with varied doses and durations of AMA treatment, involving different pathways and detailed analyses, are necessary.