Background <p>Acute kidney injury (AKI) is a critical condition that exhibits rapid deterioration in renal function, which is typically accompanied by oxidative stress and inflammation. L-carvone, a chiral monoterpenoid ketone with robust anti-oxidative and anti-inflammatory capacities.</p> Objective <p>The current research tried to examine the beneficial effect of L-carvone on AKI induced by endotoxin in mice and its underlying mechanisms.</p> Methods <p>36 BALB/c male mice were allocated into six groups: control (received normal saline only), model (obtained lipopolysaccharide (LPS) 10&#xa0;mg/kg as a single dose), and vehicle (received corn oil for five days, then LPS 10&#xa0;mg/kg on day five). The treatment groups received oral L-carvone at 25, 50 or 100&#xa0;mg/kg for five days before LPS. Kidneys and blood samples were taken twenty-24&#xa0;h following LPS injection for assessment.</p> Results <p>L-carvone substantially reduced serum concentrations of kidney injury molecule-(KIM)-1, blood urea nitrogen-(BUN), and creatinine, as well as improved renal pathological manifestations. Meanwhile, L-carvone also strikingly suppressed the inflammatory response as evidenced by significant decreases in the gene expressions of Toll-like receptor (TLR)-4, transcription factors like NF-κB, activator protein(AP)-1, and Interferon Regulatory Factor (IRF)-3 in renal tissue, resulting in attenuation of inflammatory elements, notably TNF-α and IL-1β. L-carvone also reduced the magnitude of the tubular injury score due to LPS.</p> Conclusion <p>L-carvone abrogates LPS-induced AKI, blocking the TLR4-MYD88-dependent and TRIF-dependent signaling cascade, hence attenuating structural renal injuries and enhancing kidney function. L-carvone may have beneficial effects on LPS-induced AKI.</p>

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L-carvone alleviates lipopolysaccharide-Induced acute kidney injury via modulating MyD88-dependent and independent signaling pathways in Mice

  • Saja Majeed Shareef,
  • Sarmed Hashim Kathem,
  • Hayder Ridha-Salman

摘要

Background

Acute kidney injury (AKI) is a critical condition that exhibits rapid deterioration in renal function, which is typically accompanied by oxidative stress and inflammation. L-carvone, a chiral monoterpenoid ketone with robust anti-oxidative and anti-inflammatory capacities.

Objective

The current research tried to examine the beneficial effect of L-carvone on AKI induced by endotoxin in mice and its underlying mechanisms.

Methods

36 BALB/c male mice were allocated into six groups: control (received normal saline only), model (obtained lipopolysaccharide (LPS) 10 mg/kg as a single dose), and vehicle (received corn oil for five days, then LPS 10 mg/kg on day five). The treatment groups received oral L-carvone at 25, 50 or 100 mg/kg for five days before LPS. Kidneys and blood samples were taken twenty-24 h following LPS injection for assessment.

Results

L-carvone substantially reduced serum concentrations of kidney injury molecule-(KIM)-1, blood urea nitrogen-(BUN), and creatinine, as well as improved renal pathological manifestations. Meanwhile, L-carvone also strikingly suppressed the inflammatory response as evidenced by significant decreases in the gene expressions of Toll-like receptor (TLR)-4, transcription factors like NF-κB, activator protein(AP)-1, and Interferon Regulatory Factor (IRF)-3 in renal tissue, resulting in attenuation of inflammatory elements, notably TNF-α and IL-1β. L-carvone also reduced the magnitude of the tubular injury score due to LPS.

Conclusion

L-carvone abrogates LPS-induced AKI, blocking the TLR4-MYD88-dependent and TRIF-dependent signaling cascade, hence attenuating structural renal injuries and enhancing kidney function. L-carvone may have beneficial effects on LPS-induced AKI.