ABSTRACT
PURPOSE: To evaluate the ability of dexamethasone to protect against cisplatin (CDDP)-induced ototoxicity. METHODS: Male Wistar rats were divided into the following three groups: 1) Control (C): 6 animals received intraperitoneal (IP) saline solution, 8 ml/kg/day for four days; 2) C + CDDP: 11 animals received 8 ml/kg/day of IP saline and, 90 min after saline administration, 8 mg/kg/day of IP CDDP for four days; and 3) DEXA15 + CDDP: 11 animals received IP dexamethasone 15 mg/kg/day and, 90 min after dexamethasone administration, received 8 mg/kg/day of IP CDDP for four days. RESULTS: It was found that dexamethasone did not protect against weight loss in CDDP-exposed animals. The mortality rate was comparable with that previously reported in the literature. The auditory threshold of animals in the DEXA15 + CDDP group was not significantly altered after exposure to CDDP. The stria vascularis of animals in the DEXA15 + CDDP group was partially preserved after CDDP exposure. CONCLUSIONS: Dexamethasone at the dose of 15 mg/kg/day partially protected against CDDP-induced ototoxicity, based on functional evaluation by brainstem evoked response audiontry (BERA) and morphological evaluation by optical microscopy. However, dexamethasone did not protect against systemic toxicity.
Subject(s)
Antineoplastic Agents/toxicity , Auditory Threshold/drug effects , Cisplatin/toxicity , Cochlea/drug effects , Dexamethasone/therapeutic use , Protective Agents/therapeutic use , Animals , Male , Models, Animal , Rats , Rats, WistarABSTRACT
Abstract Purpose: To evaluate the ability of dexamethasone to protect against cisplatin (CDDP)-induced ototoxicity. Methods: Male Wistar rats were divided into the following three groups: 1) Control (C): 6 animals received intraperitoneal (IP) saline solution, 8 ml/kg/day for four days; 2) C + CDDP: 11 animals received 8 ml/kg/day of IP saline and, 90 min after saline administration, 8 mg/kg/day of IP CDDP for four days; and 3) DEXA15 + CDDP: 11 animals received IP dexamethasone 15 mg/kg/day and, 90 min after dexamethasone administration, received 8 mg/kg/day of IP CDDP for four days. Results: It was found that dexamethasone did not protect against weight loss in CDDP-exposed animals. The mortality rate was comparable with that previously reported in the literature. The auditory threshold of animals in the DEXA15 + CDDP group was not significantly altered after exposure to CDDP. The stria vascularis of animals in the DEXA15 + CDDP group was partially preserved after CDDP exposure. Conclusions: Dexamethasone at the dose of 15 mg/kg/day partially protected against CDDP-induced ototoxicity, based on functional evaluation by brainstem evoked response audiontry (BERA) and morphological evaluation by optical microscopy. However, dexamethasone did not protect against systemic toxicity.
Subject(s)
Animals , Male , Rats , Auditory Threshold/drug effects , Dexamethasone/therapeutic use , Cisplatin/toxicity , Cochlea/drug effects , Protective Agents/therapeutic use , Antineoplastic Agents/toxicity , Rats, Wistar , Models, AnimalABSTRACT
BACKGROUND/AIMS: Cisplatin is a chemotherapeutic agent. The use of remote ischemic preconditioning (RIPC) was proposed after the observation that ischemic preconditioning of a cardiac vascular area could protect another completely distinctly. METHODS: This is an experimental study. Male Wistar rats were anesthetized, and they underwent a hearing evaluation via measurement of the brainstem auditory evoked potential (BSAEP). Then, cisplatin was administered intraperitoneally (IP) at a dose of 8 mg/kg/day for 4 consecutive days to group 1, whereas saline solution was administered IP to group 2. In groups 3 and 4, ischemia of the right hind paw was performed for 10 min, followed by reperfusion for 30 min, after which cisplatin or saline was administered IP to group 3 or group 4, respectively. Afterwards, all animals were evaluated via the BSAEP. The right cochlea was dissected for immunohistochemistry. RESULTS: RIPC lowered the increase in BSAEP of the animals treated with cisplatin (p = 0.0146). Weight loss decreased in the animals subjected to RIPC (p < 0.005). In group 3, RIPC reversed immunostaining for tumor necrosis factor-α and inducible nitric oxide synthase in the stria vascularis injured by cisplatin (p < 0.05). CONCLUSION: RIPC protects against systemic toxicity and ototoxicity induced by cisplatin in rats.