Protective effects of curcumin on acute gentamicin-induced nephrotoxicity in rats.
BACKGROUND
Gentamicin-induced nephrotoxicity is one of the most common causes of acute kidney injury (AKI). The phenotypic alterations that contribute to acute kidney injury include inflammatory response and oxidative stress. Curcumin has a wide range biological functions, especially as an antioxidant. This study was designed to evaluate the renoprotective effects of curcumin treatment in gentamicin-induced AKI.


METHODS
Gentamicin-induced AKI was established in female Sprague-Dawley rats. Rats were treated with curcumin (100 mg/kg body mass) by intragastric administration, once daily, followed with an intraperitoneal injection of gentamicin sulfate solution at a dose of 80 mg/kg body mass for 8 consecutive days. At days 3 and 8, the rats were sacrificed, and the kidneys and blood samples were collected for further analysis.


RESULTS
The animals treated with gentamicin showed marked deterioration of renal function, together with higher levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in the plasma as compared with the controls. Animals that underwent intermittent treatment with curcumin exhibited significant improvements in renal functional parameters. We also observed that treatment with curcumin significantly attenuated renal tubular damage, apoptosis, and oxidative stress. Curcumin treatment exerted anti-apoptosis and anti-oxidative effects by up-regulating Nrf2/HO-1 and Sirt1 expression.


CONCLUSIONS
Our data clearly demonstrate that curcumin protects kidney from gentamicin-induced AKI via the amelioration of oxidative stress and apoptosis of renal tubular cells, thus providing hope for the amelioration of gentamicin-induced nephrotoxicity.
Nephrology Department, 2nd Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan, 139 Renmin Road, Changsha, Hunan 410011, People's Republic of China.
Liyu
L
He
Xiaofei
X
Peng
Jiefu
J
Zhu
Guoyong
G
Liu
Xian
X
Chen
Chengyuan
C
Tang
Hong
H
Liu
Fuyou
F
Liu
Youming
Y
Peng
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000097:blood; D003474:Curcumin / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005839:Gentamicins / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009393:Nephritis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015815:Cell Adhesion Molecules; D003474:Curcumin; D005839:Gentamicins; D000071068:Lipocalin-2; D054834:Lipocalins; D051267:NF-E2-Related Factor 2; D056564:Sirtuin 1; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat; C495637:Nfe2l2 protein, rat; C488368:Sirt1 protein, rat
HO-1; Nrf2; Sirt1; apoptose; apoptosis; oxidative stress; stress oxydant