title: Capsaicin ameliorates cisplatin-induced renal injury through induction of heme oxygenase-1.
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.
authors.affiliation: Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine, Iksan 570-749, Korea ; Brain Korea 21 Plus Program and Department of Smart Life-Care Convergence, Wonkwang University, Graduate School, Iksan 570-749, Korea.
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Jung
authors.forename: Hyung-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Gi-Su
authors.initials: GS
authors.lastname: Oh
authors.forename: AiHua
authors.initials: A
authors.lastname: Shen
authors.forename: Subin
authors.initials: S
authors.lastname: Lee
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Choe
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002211:Capsaicin / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002945:Cisplatin / Q000009:adverse effects*; D004790:Enzyme Induction / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D008565:Membrane Proteins; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D002945:Cisplatin; D002211:Capsaicin