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Capsaicin ameliorates cisplatin-induced renal injury through induction of heme oxygenase-1.

Molecules and cells (2014-03-20)
Sung-Hyun Jung, Hyung-Jin Kim, Gi-Su Oh, AiHua Shen, Subin Lee, Seong-Kyu Choe, Raekil Park, Hong-Seob So
ABSTRACT

Cisplatin is one of the most potent chemotherapy agents. However, its use is limited due to its toxicity in normal tissues, including the kidney and ear. In particular, nephrotoxicity induced by cisplatin is closely associated with oxidative stress and inflammation. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in the heme metabolism, has been implicated in a various cellular processes, such as inflammatory injury and anti-oxidant/oxidant homeostasis. Capsaicin is reported to have therapeutic potential in cisplatin-induced renal failures. However, the mechanisms underlying its protective effects on cisplatin-induced nephrotoxicity remain largely unknown. Herein, we demonstrated that administration of capsaicin ameliorates cisplatin-induced renal dysfunction by assessing the levels of serum creatinine and blood urea nitrogen (BUN) as well as tissue histology. In addition, capsaicin treatment attenuates the expression of inflammatory mediators and oxidative stress markers for renal damage. We also found that capsaicin induces HO-1 expression in kidney tissues and HK-2 cells. Notably, the protective effects of capsaicin were completely abrogated by treatment with either the HO inhibitor ZnPP IX or HO-1 knockdown in HK-2 cells. These results suggest that capsaicin has protective effects against cisplatin-induced renal dysfunction through induction of HO-1 as well as inhibition oxidative stress and inflammation.

MATERIALS
Product Number
Brand
Product Description

Supelco
Creatinine, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Hematoxylin
Sigma-Aldrich
Hematoxylin, certified by the Biological Stain Commission
Sigma-Aldrich
cis-Diammineplatinum(II) dichloride, crystalline
Sigma-Aldrich
trans-Platinum(II)diammine dichloride
Cisplatin, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Creatinine, anhydrous, ≥98%
Sigma-Aldrich
cis-Diamineplatinum(II) dichloride, ≥99.9% trace metals basis
Cisplatin impurity A, European Pharmacopoeia (EP) Reference Standard
USP
Transplatin, United States Pharmacopeia (USP) Reference Standard