Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury.

Abstract

Sepsis is the major cause of acute kidney injury (AKI) in severely ill patients, but only limited therapeutic options are available. During sepsis, lipopolysaccharide (LPS), an endotoxin derived from bacteria, activates signaling cascades involved in inflammatory responses and tissue injury. Apamin is a component of bee venom and has been shown to exert antioxidative, antiapoptotic, and anti-inflammatory activities. However, the effect of apamin on LPS-induced AKI has not been elucidated. Here, we show that apamin treatment significantly ameliorated renal dysfunction and histological injury, especially tubular injury, in LPS-injected mice. Apamin also suppressed LPS-induced oxidative stress through modulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and heme oxygenase-1. Moreover, tubular cell apoptosis with caspase-3 activation in LPS-injected mice was significantly attenuated by apamin. Apamin also inhibited cytokine production and immune cell accumulation, suppressed toll-like receptor 4 pathway, and downregulated vascular adhesion molecules. Taken together, these results suggest that apamin ameliorates LPS-induced renal injury through inhibiting oxidative stress, apoptosis of tubular epithelial cells, and inflammation. Apamin might be a potential therapeutic option for septic AKI.

• Authors: Jung-Yeon Kim, Jaechan Leem, Kwan-Kyu Park
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 25 Issue 23 (Dec 03 2020) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 33287398 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Cytokines
• Lipopolysaccharides
• Apamin

Topics

• Acute Kidney Injury (chemically induced, drug therapy, metabolism)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (physiology)
• Apamin (pharmacology)
• Apoptosis (drug effects)
• Cell Adhesion (drug effects)
• Cytokines (metabolism)
• Disease Models, Animal
• Down-Regulation (drug effects)
• Epithelial Cells (drug effects, metabolism)
• Inflammation (drug therapy, metabolism)
• Kidney (drug effects, metabolism)
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Oxidative Stress (drug effects)
• Sepsis (drug therapy, metabolism)
• Signal Transduction (drug effects)