Related Experiment Videos
Mechanism of cisplatin ototoxicity: antioxidant system
R Ravi1, S M Somani, L P Rybak
1Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62794-9230, USA.
Abstract:
The dose and duration limiting toxic effects of cisplatin are ototoxicity and nephrotoxicity. While several studies have attempted to shed some light on the causes of nephrotoxicity, the reasons for ototoxicity induced by cisplatin are poorly understood. Therefore, this investigation was undertaken to delineate the potential mechanisms underlying cisplatin ototoxicity. The role of glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde levels, and antioxidant enzyme activities [superoxide dismutase, catalase, GSH peroxidase, and GSH reductase] were examined in cochlear toxicity following an acute dose of cisplatin. Male Wistar rats were treated with various doses of cisplatin. Pretreatment auditory brain stem evoked responses (ABR) were performed and then post-treatment ABRs and endocochlear potentials were also performed after three days. Acute cochlear toxicity (ototoxicity) was evidenced as elevated hearing thresholds and prolonged wave I latencies in response to various stimuli (clicks and tone bursts at 2, 8, 16 and 32 kHz) on ABRs. The endocochlear potentials were reduced (50% control) in cisplatin-treated rats as compared to control animals. The rats were sacrificed and cochleae isolated. The GSH, GSSG and malondialdehyde levels, and antioxidant enzyme activities were determined. Cisplatin ototoxicity correlated with a decrease in cochlear GSH [0.45 +/- 0.012 nmol/mg] after cisplatin administration compared to 0.95-012 nmol/mg in control cochleae (P < 0.05). Superoxide dismutase, catalase activities and malondialdehyde levels were significantly increased in the cochleae of cisplatin injected rats. Cochlear GSH-peroxidase and GSH reductase activity significantly decreased after cisplatin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Cisplatin causes hearing loss (ototoxicity) by decreasing cochlear glutathione and antioxidant enzymes. This study investigated cisplatin
Area of Science:
- Ototoxicology
- Biochemistry
- Pharmacology
Background:
- Cisplatin is a vital chemotherapy drug, but its use is limited by ototoxicity and nephrotoxicity.
- The mechanisms of cisplatin-induced ototoxicity remain poorly understood, necessitating further investigation.
Purpose of the Study:
- To investigate the biochemical mechanisms underlying cisplatin-induced ototoxicity.
- To examine the role of glutathione, its oxidized form, malondialdehyde, and antioxidant enzymes in cochlear damage.
Main Methods:
- Male Wistar rats were administered cisplatin.
- Auditory brainstem evoked responses (ABR) and endocochlear potentials were measured.
- Cochlear levels of glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde, and antioxidant enzyme activities were analyzed.
Main Results:
- Cisplatin induced ototoxicity, evidenced by elevated hearing thresholds and reduced endocochlear potentials.
- Cochlear GSH levels significantly decreased post-cisplatin administration.
- Activities of superoxide dismutase, catalase, and malondialdehyde levels increased, while GSH peroxidase and GSH reductase activities decreased.
Conclusions:
- Cisplatin ototoxicity is associated with oxidative stress and altered glutathione metabolism in the cochlea.
- These findings provide insights into the mechanisms of cisplatin-induced hearing loss.