Donny HENDRIYANTO, Sukri RAHMAN, TOFRIZAL, Aisyah ELLIYANTI
Journal of Research in Pharmacy - 2025;29(6):2386-2394
Cisplatin is effective against cancer but has serious ototoxicity side effects. Thymoquinone has been shown to be a powerful antioxidant and anti-inflammatory, and it has scavenging activity against free radicals. This study aims to determine the effects of thymoquinone on superoxide dismutase (SOD), malondialdehyde acid (MDA), and nuclear factor kappa-B (NF-kappaB) levels; signal-to-noise ratio (SNR) value of distortion product otoacoustic emission (DPOAE); and degree of outer hair cells (OHC) damage in cisplatin ototoxicity. This experimental animal study included 24 healthy male Wistar rats (Rattus norvegicus), which were divided into four groups. Group 1 was the positive control that received cisplatin alone; Groups 2 and 3 received cisplatin (15 mg/kg BW) and thymoquinone at different doses (25 mg/kg/day for Group 2 and 50 mg/kg/day for Group 3); and Group 4 was the negative control. SOD levels were measured using a colorimetric assay; MDA levels with a thiobarbituric acid reactive substances (TBAR) assay; NF-kappaB levels with an enzyme-linked immunosorbent assay (ELISA); SNR values with a DPOAE examination; and histopathology examination was performed after treatment to determine the effects of thymoquinone on reducing the ototoxicity of cisplatin. The mean of MDA and NF-kappaB levels and OHC damage increased significantly in Group 1 compared to Group 4. The mean of SOD levels and SNR values of DPOAE decreased significantly in Group 1 compared to Group 4. The administration of cisplatin and thymoquinone at 50 mg/kg/day resulted in a significant increase in SOD level and SNR value of DPOAE and a significant decrease in MDA levels, NF-kappaB, and degree of OHC damage compared with Group 1, with p < 0.05. Thymoquinone administration reduced the ototoxicity of cisplatin by improving SOD levels and SNR values of DPOAE and decreasing MDA, NF-kappaB levels, and the degree of OHC damage.
