Pretreatment of Sialic Acid Efficiently Prevents Lipopolysaccharide-Induced Acute Renal Failure and Suppresses TLR4/gp91-Mediated Apoptotic Signaling

Kidney and Blood Pressure Research

Chen C.-C.³  Hsu S.-P.²  Chien C.-T.¹ 

[1] Renal Division, Department of Internal Medicine, Far Eastern Memory Hospital, New Taipei City; $$;Department of Infectious Disease, Kuang-Tien General Hospital, Taichung, Taiwan$$

关键词: Lipopolysaccharide;    Sialic acid;    Reactive oxygen species;    Apoptosis;    Gp91;    Toll-like receptors;   

DOI  :  10.1159/000443430

来源: S Karger AG

【 摘 要 】

Background/Aims: Lipopolysaccharides (LPS) binding to Toll-like receptor 4 (TLR4) activate NADPH oxidase gp91 subunit-mediated inflammation and oxidative damage. Recognizing the high binding affinity of sialic acid (SA) with LPS, we further explored the preventive potential of SA pretreatment on LPS-evoked acute renal failure (ARF). Methods: We determined the effect of intravenous SA 30 min before LPS-induced injury in urethane-anesthetized female Wistar rats by evaluating kidney reactive oxygen species (ROS) responses, renal and systemic hemodynamics, renal function, histopathology, and molecular mechanisms. Results: LPS time-dependently reduced arterial blood pressure, renal microcirculation, and increased blood urea nitrogen and creatinine in the rats. LPS enhanced monocyte/macrophage infiltration and ROS production, and subsequently impaired kidneys with the enhancement of TLR4/NADPH oxidase gp91/Caspase 3/poly-(ADP-ribose)-polymerase (PARP)-mediated apoptosis in the kidneys. SA pretreatment effectively alleviated LPS-induced ARF. The levels of LPS-increased ED-1 infiltration and ROS production in the kidney were significantly depressed by SA pretreatment. Furthermore, SA pretreatment significantly depressed TLR4 activation, gp91 expression, and Caspase 3/PARP induced apoptosis in the kidneys. Conclusion: We suggest that pretreatment of SA significantly and preventively attenuated LPS-induced detrimental effects on systemic and renal hemodynamics, renal ROS production and renal function, as well as, LPS-activated TLR4/gp91/Caspase3 mediated apoptosis signaling.

【 授权许可】

Unknown