Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway.

Abstract

OBJECTIVES:

To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism.

METHODS:

Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors.

RESULTS:

After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p < .05) and ameliorated the contrast-induced acute kidney injury (p < .05) and significantly reduced Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (Myd88), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression and relative mRNA expression levels (p < .05) and significantly decreased expression levels of downstream inflammatory factors (p < .05).

CONCLUSION:

Different atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

• Authors: Rongzheng Yue, Chuan Zuo, Jing Zeng, Baihai Su, Ye Tao, Songmin Huang, Rui Zeng
• Journal: Renal failure (Ren Fail) Vol. 39 Issue 1 Pg. 643-651 (Nov 2017) ISSN: 1525-6049 [Electronic] England
• PMID: 28805489 (Publication Type: Journal Article)

Chemical References

• Contrast Media
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Myd88 protein, rat
• Myeloid Differentiation Factor 88
• NF-kappa B
• RNA, Messenger
• Tlr4 protein, rat
• Toll-Like Receptor 4
• Atorvastatin
• Creatinine

Topics

• Acute Kidney Injury (blood, chemically induced, prevention & control)
• Animals
• Atorvastatin (pharmacology, therapeutic use)
• Blood Urea Nitrogen
• Contrast Media (adverse effects)
• Creatinine (blood)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Kidney Function Tests
• Kidney Tubules (drug effects, pathology)
• Male
• Myeloid Differentiation Factor 88 (metabolism)
• NF-kappa B (metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (metabolism)