Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation.
BACKGROUND
Cisplatin is a chemotherapeutic agent used in treatment of malignant tumours. However, cisplatin produces various side effects, such as nephrotoxicity, neurotoxicity, emetogenesis and ototoxicity. Inflammation is an important mechanism of cisplatin nephrotoxicity. Alpha-lipoic acid (alpha-LA) has anti-inflammatory effects that inhibit both adhesion molecule expression in human endothelial cells and monocyte adhesion by suppressing the nuclear factor-kappaB (NF-kappaB) signalling pathway. The goals of this study were to investigate the anti-inflammatory effects of alpha-LA during cisplatin-induced renal injury and to examine the mechanisms of protection.


METHODS
C57BL/6 mice were given cisplatin (20 mg/kg) with or without alpha-LA treatment (100 mg/kg for 3 days). Renal function, histological changes, adhesion molecule expression and inflammatory cell infiltration were examined. The effect of alpha-LA on NF-kappaB activity was evaluated by examining nuclear translocation and phosphorylation of NF-kappaB p65 subunits in kidney tissue.


RESULTS
Cisplatin-induced decreases in renal function, measured by blood urea nitrogen, serum creatinine level and renal tubular injury scores, were attenuated by alpha-LA treatment. alpha-LA decreased the tissue levels of tumour necrosis factor-alpha, the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and suppressed the infiltration of CD11b-positive macrophages. alpha-LA also attenuated the cisplatin-induced increases in the phosphorylation and nuclear translocation of NF- kappaB p65 subunits in kidney tissue.


CONCLUSIONS
These results suggest that alpha-LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-kappaB activity.
Kang
Kyung Pyo
KP
Department of Internal Medicine and Renal Regeneration Laboratory, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Kim
Duk Hoon
DH
Jung
Yu Jin
YJ
Lee
Ae Sin
AS
Lee
Sik
S
Lee
Sang Yong
SY
Jang
Kyu Yun
KY
Sung
Mi Jeong
MJ
Park
Sung Kwang
SK
Kim
Won
W
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000139:chemically induced* / Q000517:prevention & control*; D008063:Thioctic Acid / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D008063:Thioctic Acid; D002945:Cisplatin