HYPOTHESIS: To investigate whether curcumin may have in vivo protective effects against cisplatin ototoxicity by its direct scavenger activity and/or by curcumin-mediated upregulation of HO-1. BACKGROUND: Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. A protective approach to decrease cisplatin ototoxicity without compromising its therapeutic efficacy remains a critical goal for anticancer therapy. Recent evidences indicate that curcumin exhibits antioxidant, anti-inflammatory, and chemosensitizer activities. METHODS: In male adult Wistar rats, a curcumin dose of 200 mg/kg, selected from a dose-response curve, was injected 1 hour before cisplatin administration and once daily for the following 3 days. A single dose of cisplatin (16 mg/kg) was administered intraperitoneally. Rats were divided as follows: 1) control, 2) curcumin control, 3) vehicle control, 4) cisplatin, 5) cisplatin+ vehicle, and 6) curcumin+cisplatin. ABRs were measured before and at Days 3 and 5 after cisplatin administration. Rhodamine-phalloidin staining, 4-hydroxy-2-nonenal and heme-oxigenase-1 immunostainings, and Western blot analyses were performed to assess and quantify OHC loss, lipid peroxidation, and the endogenous response to cisplatin-induced damage and to curcumin protection. RESULTS: Curcumin treatment attenuated hearing loss induced by cisplatin, increased OHC survival, decreased 4-HNE expression, and increased HO-1 expression. CONCLUSION: This preclinical study demonstrates that systemic curcumin attenuates ototoxicity and provides molecular evidence for a role of HO-1 as an additional mediator in attenuating cisplatin-induced damage.
HYPOTHESIS: To investigate whether curcumin may have in vivo protective effects against cisplatinototoxicity by its direct scavenger activity and/or by curcumin-mediated upregulation of HO-1. BACKGROUND:Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. A protective approach to decrease cisplatinototoxicity without compromising its therapeutic efficacy remains a critical goal for anticancer therapy. Recent evidences indicate that curcumin exhibits antioxidant, anti-inflammatory, and chemosensitizer activities. METHODS: In male adult Wistar rats, a curcumin dose of 200 mg/kg, selected from a dose-response curve, was injected 1 hour before cisplatin administration and once daily for the following 3 days. A single dose of cisplatin (16 mg/kg) was administered intraperitoneally. Rats were divided as follows: 1) control, 2) curcumin control, 3) vehicle control, 4) cisplatin, 5) cisplatin+ vehicle, and 6) curcumin+cisplatin. ABRs were measured before and at Days 3 and 5 after cisplatin administration. Rhodamine-phalloidin staining, 4-hydroxy-2-nonenal and heme-oxigenase-1 immunostainings, and Western blot analyses were performed to assess and quantify OHC loss, lipid peroxidation, and the endogenous response to cisplatin-induced damage and to curcumin protection. RESULTS:Curcumin treatment attenuated hearing loss induced by cisplatin, increased OHC survival, decreased 4-HNE expression, and increased HO-1 expression. CONCLUSION: This preclinical study demonstrates that systemic curcumin attenuates ototoxicity and provides molecular evidence for a role of HO-1 as an additional mediator in attenuating cisplatin-induced damage.
Authors: Laura Astolfi; Edi Simoni; Filippo Valente; Sara Ghiselli; Stavros Hatzopoulos; Milvia Chicca; Alessandro Martini Journal: PLoS One Date: 2016-09-15 Impact factor: 3.240