Cisplatin-induced Ototoxicity In Rats Research Articles

Possible ameliorative effects of pentoxifylline on cisplatin-induced ototoxicity in rats: a study with hearing test, light, and scanning electron microscopy

Cisplatin is an antineoplastic drug widely used to treat various types of cancer. Ototoxicity is still cisplatin’s most critical side-effect. Some patients may experience dose limitations due to hearing loss. Pentoxifylline (PX) exhibits powerful antioxidant, anti-inflammatory, and immune-regulatory effects. Our study was designed to investigate the protective effects of pentoxifylline on cisplatin-induced ototoxicity. Forty adult male healthy Sprague-Dawley rats were used through the entire experiment. Four groups of animals were categorized: Group I (control group); Group II (PX group) received 25 mg/kg/day of oral PX by gavage for 8 consecutive days; Group III (Cisplatin group) received cisplatin single intraperitoneal dose of 10 mg/kg; Group IV (PX + Cisplatin group) received 25 mg/kg/day of oral PX by gavage for 8 successive days and a single intraperitoneal dose of 10 mg/kg cisplatin at the 4th day. First and 9th-day Distortiondistortion-product otoacoustic emissions (DPOAE) tests were conducted. An intracardiac blood sample was collected for total antioxidant capacity (TAC) measurement, and the cochleae of rats were examined histopathologically. A significant reduction in serum TAC value was detected in the cisplatin group, while PX treatment significantly reduced TAC. Cisplatin decreased the DPOAE amplitudes in rats; conversely, the PX+cisplatin group showed a significant increase at all frequencies. Upon histopathological examination, the Ciplastin group revealed perturbation of the normal architecture of the organ of Corti, increased collagen deposition and marked expression of caspase-3, while the PX+cisplatin group revealed preserved architecture of the organ of Corti, minimal collagen deposition and downregulation of Caspase-3 expression. As evidenced by our findings and results from DPOAE results, biochemical findings, histological and ultrastructural analyses, PX significantly protects rats against ototoxicity caused by cisplatin.

Amelioration of Cisplatin-Induced Ototoxicity in Rats by L-arginine: The Role of Nitric Oxide, Transforming Growth Factor Beta 1 and Nrf2/HO-1 Pathway

Background:Cisplatin is an alkylating agent that inhibits DNA replication and interferes with proliferation of cancer cells. However, the major limiting factor for its use is the possible development of adverse effects, including ototoxicity. Up till now, the mechanisms of this ototoxicity remain poorly understood. However, induction of oxidative stress and activation of the inflammatory cascade were suggested as contributing factors. Purpose:The aim of this study was to explore the effect of L-arginine on cisplatin-induced ototoxicity in rats. Methods:Thirty male adult Wistar rats were divided into three equal groups as follows: control group; cisplatin group and cisplatin + L-arginine group. Auditory brainstem response (ABR), tissue oxidative stress parameters, total nitrate/nitrite, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) content, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α) and interleukin 15 (IL-15) were assessed. Also, the cochlear tissues were subjected to histopathological and electron microscopic examination. Results:Administration of L-arginine to cisplatin-treated rats induced significant decrease in the average ABR threshold shifts at all frequencies, tissue TGF-β1, TNF-α and IL-15 associated with significant increase in tissue antioxidant enzymes, total nitrate/nitrite and Nrf2/HO-1 content compared to cisplatin group. Also, pretreatment of cisplatin-injected rats with L-arginine induced significant improvement of the histopathological and electron microscopic picture compared to cisplatin group. Conclusion:L-arginine may serve as a promising therapeutic modality for amelioration of cisplatin-induced ototoxicity.

Assessment of the Effectiveness of Quercetin on Cisplatin-Induced Ototoxicity in Rats.

This study aimed to evaluate the effect of quercetin on cochlear function and morphology, and its possible protective effect against acute cisplatin-induced ototoxicity in rats. This prospective and controlled animal study was conducted on Wistar albino rats divided into four groups. Otoacoustic emission measures were performed three days after the first infiltration in Group 1 (saline), 2 (cisplatin), and 3 (quercetin). This interval was five days for Group 4 (cisplatin+quercetin). At the end of the study, the rats were decapitated with deep anesthesia, and histological changes in the cochleas were observed by light microscopy. Group 2 (cisplatin) revealed significant differences between the first and second measures in all frequencies. When compared to other group, the difference of the changes in Group 2 statistically significantly decreased, especially in higher frequencies. Morphologically, there were no acute changes in Group 1 and Group 3. Outer hair cell loss and the degeneration of stria vascularis and spiral ganglion were observed in both Groups 2 and 4; the damages in the latter were lesser. Quercetin does not have negative effect on cochlea, and it has protective effect on cisplatin-induced ototoxicity.

Protective Effect of Melatonin on Cisplatin-induced Ototoxicity in Rats.

Cisplatin is a highly effective chemotherapeutic agent that is used to treat solid tumors; however, its severe side effects remain a limitation. In particular, the high incidence of cisplatin-induced ototoxicity has attracted interest. Melatonin has been shown to decrease the toxic effects of cisplatin due to its antioxidant activity, and could increase the efficacy of cancer chemotherapy. The aim of this study was to determine the effect of melatonin against ototoxicity in rats treated with cisplatin. Rats were randomly divided into four groups (saline, melatonin, cisplatin+saline, and melatonin+cisplatin). Distortion-product otoacoustic emission (DPOAE) measurements were carried out on days 1 and 8. There was a decrease in DPOAE amplitudes in the animals that received cisplatin (10 mg/kg); however, the group treated with cisplatin+melatonin presented DPOAE amplitudes comparable to those of the control groups. Melatonin can be used as an adjuvant tumor treatment due to its ability to decrease cisplatin-induced ototoxicity.

Evaluation of sleep quality and daytime sleepiness in nurses

Aim: In this study, it was aimed to experimentally investigate the protective effects of melatonin in the cisplatin-induced ototoxicity.Material and Methods: Ten Wistar-albino rats were included in the study. Two equal groups were generated randomly as cisplatin and melatonin groups. Rats’ underwent Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emission (DPOAE) testing before the drug administration and the results were recorded. Both tests were repeated 72 hours after the cisplatin administration in all rats.Results: Significant difference was found between the I-IV interval values before the treatment and after the treatment both in cisplatin and melatonin group. As well as the significant difference in hearing threshold value changes, statistically, significant differences in ABR-I and ABR-IV interval variations were also seen between the cisplatin and melatonin groups. A statistically significant decrease was found between the initial and final control SNR (signal-to-noise ratio) levels within the cisplatin group in the evaluations at 2000Hz, 3000Hz and 4000Hz. Statistically, significant differences were observed between SNR levels when the melatonin group was compared with the cisplatin group. Conclusion: Melatonin appears to reduce cisplatin-induced ototoxicity in rats. Although, the use of supplementary therapies targeting to reduce the toxic effects in clinical studies is still a controversial point.

Does melatonin alleviate ototoxic effect caused by administration of cisplatin?

Aim: In this study, it was aimed to experimentally investigate the protective effects of melatonin in the cisplatin-induced ototoxicity.Material and Methods: Ten Wistar-albino rats were included in the study. Two equal groups were generated randomly as cisplatin and melatonin groups. Rats’ underwent Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emission (DPOAE) testing before the drug administration and the results were recorded. Both tests were repeated 72 hours after the cisplatin administration in all rats.Results: Significant difference was found between the I-IV interval values before the treatment and after the treatment both in cisplatin and melatonin group. As well as the significant difference in hearing threshold value changes, statistically, significant differences in ABR-I and ABR-IV interval variations were also seen between the cisplatin and melatonin groups. A statistically significant decrease was found between the initial and final control SNR (signal-to-noise ratio) levels within the cisplatin group in the evaluations at 2000Hz, 3000Hz and 4000Hz. Statistically, significant differences were observed between SNR levels when the melatonin group was compared with the cisplatin group. Conclusion: Melatonin appears to reduce cisplatin-induced ototoxicity in rats. Although, the use of supplementary therapies targeting to reduce the toxic effects in clinical studies is still a controversial point.

Is Hyperbaric Oxygen Therapy Effective in Cisplatin-Induced Ototoxicity in Rats?

ObjectivesCisplatin is an antineoplastic agent, used in the treatment of different types of malignant neoplasms. Side effects such as ototoxicity, nephrotoxicity, and bone marrow toxicity are the main limitations of its clinical use. The aim of the present study was to evaluate the possible effects of hyperbaric oxygen (HBO) therapy as a protective agent in cisplatin-induced ototoxicity in rats.MethodsA total of 30 adult Wistar rats (60 ears) were divided into five equal groups. Group 1 is a control group; group 2 is HBO therapy group; group 3 received 15 mg/kg cisplatin intraperitoneally; group 4 received 15 mg/kg cisplatin intraperitoneally and HBO treatment on the same day; group 5 received 15 mg/kg cisplatin intraperitoneally and HBO treatment 72 hours later. The effect of ototoxicity was measured with distortion product otoacoustic emission testing performed on the days 1, 3, and 7.ResultsGroups 4 and 5 that received HBO treatment after cisplatin had better signal-to-noise ratio (SNR) values compared with group 3 that received only cisplatin (P<0.05). Compared with group 5, group 4 (same day HBO treatment) had better SNR values (P<0.05).ConclusionHBO was found effective for prevention of cisplatin-induced ototoxicity in rats. Our study differs from other studies regarding using a promising treatment, which does not expose subjects to extra stress.

Protective effect of gallic acid against cisplatin-induced ototoxicity in rats

IntroductionCisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. ObjectiveThe purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. MethodsTwenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each. Cisplatin group received a single intraperitoneal dose of 15mg/kg cisplatin. Gallic acid group received intraperitoneal gallic acid at 100mg/kg for five consecutive days. Cisplatin+gallic acid group received intraperitoneal gallic acid at 100mg/kg for five consecutive days and a single intraperitoneal dose of 15mg/kg cisplatin at 3rd day. A control group received 1mL intraperitoneal saline solution for five consecutive days. Prior to drug administration, all rats were exposed to the distortion product otoacoustic emissions test. The test was repeated on the 6th day of the study. All rats were then sacrificed; the cochleas were removed and set aside for biochemical and histopathological analyses. ResultsIn cisplatin group, Day 6 signal noise ratio values were significantly lower than those of the other groups. Also, malondialdehyde levels in cochlear tissues were significantly higher, superoxide dismutase and glutathione peroxidase activities were significantly lower compared to the control group. Histopathologic evaluation revealed erosion in the stria vascularis, degeneration and edema in the connective tissue layer in endothelial cells, impairment of outer hair cells and a decrease in the number of these calls. In the cisplatin+gallic acid group, this biochemical, histopathological and functional changes were reversed. ConclusionIn the light of our findings, we think that gallic acid may have played a protective role against cisplatin-induced ototoxicity in rats, as indicated by the distortion product otoacoustic emissions test results, biochemical findings and immunohistochemical analyses.

The protective effect of coumaric acid against cisplatin-induced ototoxicity in rats

Cis-diammineedichloroplatinum (cisplatin) is a chemotherapeutic agent used for the treatment of several types of cancer. However, severe side-effects such as ototoxicity, nephrotoxicity and neurotoxicity restrict its use. p-Coumaric acid (PCA) is a phenol class compound obtained from various plants in nature such as grape, carrot and tomato and from beverages such as tea and beer. It was shown to have antioxidant and free radical scavenging, anti-inflammatory and neuroprotective effects. The purpose of this study was to perform a biochemical and histopathological evaluation of the protective efficacy of PCA in ototoxicity induced with cisplatin in rats. To the best of our knowledge, no previous research has investigated the protective effect of PCA against cisplatin-induced ototoxicity. 28 Wistar rats were used. The animals were randomly divided into four groups of seven members each. No drug was administered to the rats in the control group, while the cisplatin group received a single intraperitoneal dose of 10 mg/kg cisplatin. PCA was administered to the PCA group rats by the intraperitoneal route for three days at a dose of 100 mg/kg. In the cisplatin+PCA group, intraperitoneal PCA at 100 mg/kg was administered one hour after injection of 10 mg/kg intraperitoneal cisplatin for three consecutive days. Rats were sacrificed 24 h after the final drug administration. The cochlear tissues were removed and MDA levels, GPx and SOD activities were measured to evaluate the oxidative stress status and histopathological evaluation was performed to reveal cochlear damage. The results showed that PCA protects the cochlea from ototoxic effect of cisplatin. PCA is a reliable agent that provides significant biochemical and histopathological protection against cisplatin-induced ototoxicity in rats.

The effect of ferulic acid against cisplatin-induced ototoxicit

Ototoxicity refers to cellular damage or functional disorder developing in the inner ear in association with any therapeutic agent or chemical substance. Cisplatin, one of these agents capable of causing ototoxicity, is a chemotherapeutic used in several malignancies. Ferulic acid (FA) is a phenolic acid with known anti-oxidative and anti-inflammatory properties. The purpose of this study was to perform a biochemical and histopathological investigation of the protective efficacy of FA against cisplatin-induced ototoxicity in rats. Twenty-four Wistar rats were used in this study. Animals were randomly assigned into four groups of six rats each. Rats in the control group received intraperitoneal injection of 1 ml salin for four consecutive days. Rats in the cisplatin group received a single intraperitoneal administration of 10 mg/kg cisplatin. Rats in the FA group received intraperitoneal FA at 100 mg/kg for four days, and rats in the cisplatin+FA group received intraperitoneal FA at 100 mg/kg 1 h after administration of intraperitoneal cisplatin at 10 mg/kg, this procedure being performed for four consecutive days. Rats were sacrificed 24 h after the final drug administration. Cochlear tissues were removed for biochemical and histopathological analysis. MDA levels were significantly higher in cochlear tissues of the rats receiving cisplatin compared to the control group. MDA levels in rats receiving cisplatin and treated with FA were significantly lower than those in the cisplatin group. Activities of SOD and GPx decreased significantly in the cochleas of rats administered cisplatin compared to the control group. Both SOD and GPx activities were significantly higher in rats administered FA and cisplatin in combination compared to the cisplatin only. Histopathological evaluation of cochleas of the rats revealed significant protection of FA against cisplatin induced ototoxicity. This study, the first in the literature, shows that FA exhibits a protective effect against cisplatin-induced ototoxicity.

The protective effects of whortleberry extract against cisplatin-induced ototoxicity in rats

IntroductionCisplatin is one of the main chemotherapeutic agents used for the treatment of many types of cancer. However, ototoxicity, one of the most serious side effects of cisplatin, restricts its usage. ObjectiveWe aimed to investigate the protective effects of whortleberry extract against cisplatin-induced ototoxicity by evaluating hearing and histopathological cochlear damage and by measuring the biochemical parameters affected byoxidative stress. MethodsForty-eight male rats were included in the study after performing Distortion Product Otoacoustic Emission test to confirm that their hearing levels were normal. The rats were randomly divided into six groups: the control group, the sham group, and, which received only whortleberry extract, only cisplatin, cisplatin+100mg whortleberry extract, cisplatin+200mg whortleberry extract, respectively. Audiologic investigation was performed by performing the Distortion Product Otoacoustic Emission test at the beginning and at the eighth day of the study. Cardiac blood samples were collected for biochemical analysis, and the rats were sacrificed to obtain cochlear histopathological specimens on the eighth day. ResultsThe results revealed that whortleberry protects hearing against cisplatin-induced ototoxicity independent of the dose. However, high doses of whortleberry extract are needed to prevent histopathological degeneration and oxidative stress. ConclusionThe results obtained in this study show that whortleberry extract has a protective effect against cisplatin-induced ototoxicity.

Study of the protective effect of dexamethasone on cisplatin-induced ototoxicity in rats.

To evaluate the ability of dexamethasone to protect against cisplatin (CDDP)-induced ototoxicity. 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. 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. 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.

The protective role of tetramethylpyrazine against cisplatin-induced ototoxicity

ObjectivesThe aim of the present study was to investigate the protective effect of tetramethylpyrazine (TMP) on cisplatin-induced ototoxicity in rats. MethodsForty healthy, female, 24-week-old, Sprague-Dawley rats (n = 40) were randomly assigned to four groups as follows: group one (n = 10) received intraperitoneal (i.p.) physiological saline at daily doses of 3 mg/kg for seven days; group two (n = 10) received a single dose of i.p. 15 mg/kg cisplatin; group three (n = 10) received i.p. 140 mg/kg TMP daily for seven days plus a single dose of i.p. 15 mg/kg cisplatin on the fourth day; group four (n = 10) received i.p. 140 mg/kg TMP daily for seven days. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements were obtained from the animals (40 rats, 80 ears) under general anesthesia before and after drug administration. The temporal bulla of animals were bilaterally removed for immunohistopathological examination. ResultsIn group two, DPOAE and ABR values were significantly deteriorated after drug administration, whereas there was no statistically significant difference between the pre- and posttreatment DPOAE and ABR values for all frequencies for groups one, three and four. The mean scores for external ciliated cells (ECCs), stria vascularis (SV) and spiral ganglion (SG) injuries in hematoxylin and eosin (H&E) staining, and also caspase-3 immunoreactivity were significantly higher in group two than in the other groups. ConclusionIn the present study, the protective effect of TMP on cisplatin ototoxicity was demonstrated through studies of electrophysiology and immunohistopathology. Co-administration of TMP may have potential protective effects against cisplatin-induced ototoxicity.

Koenzim Q10'un ratlarda sıçanlarda sisplatinin neden olduğu ototoksisiteye etkisi

Koenzim Q10'un ratlarda sıçanlarda sisplatinin neden olduğu ototoksisiteye etkisi

Protective Effect of Selenium Against Cisplatin-Induced Ototoxicity in an Experimental Design.

Cisplatin is an effective chemotherapeutic agent in the treatment of several types of malignant solid tumors but its clinical use is associated with ototoxicity. In the present study, we investigated the effect of selenium administration on lipid peroxidation (malondialdehyde [MDA]) and cisplatin-induced ototoxicity in rats. Healthy wistar albino rats (n = 21) were randomly divided into 3 groups: control (C), cisplatin (Cis), cisplatin and selenium (Cis+Se). Cisplatin was administered for 3 days to Cis and Cis+Se groups. Cis+Se group received selenium 5 days before cisplatin injection and continued for 11 consecutive days. Hearing thresholds and lipid peroxidation (MDA) levels of the rats were recorded before injections and at the end of experimental protocol. The cochleas of animals were harvested for histologic and immunuhistochemical examinations. In biochemichal analyses, pretreatment with selenium prevented the elevation of MDA levels in Cis+Se group rats. Moreover, animals in Cis+Se group had better hearing threshold levels than animals in cis group. Samples obtained from the animals in Cis group revealed extensive loss of the normal microarchitecture of the organ of Corti. On the other hand, animals in Cis+Se group exhibited a preservation of the morphology of the organ of Corti and outer hair cells. In the immunohistochemical examinations of cochlear tissues stained with anti-caspase-3, a higher degree of immunopositivity was found in the Cis group. When Cis+Se group and Cis group were compared, significantly less immunopositivity occurred in the Cis+Se group (P < 0.05). Thus, it appears that pretreatment with selenium may reduce cisplatin-induced ototoxicity in rats.

Intraperitoneal curcumin and vitamin E combination for the treatment of cisplatin-induced ototoxicity in rats

IntroductionCisplatin ototoxicity is characterized by irreversible, progressive, bilateral sensorineural hearing loss at high frequencies, accompanied by tinnitus. The aim of this study is to demonstrate the protective action of curcumin alone or in combination with vitamin E against cisplatin-induced ototoxicity in animal models. Material and methodsThe study included 42 rats. Experimental animals were randomized into 6 groups. In the first group, intra-peritoneal cisplatin was administered alone. In the second group, intra-peritoneal cisplatin and curcumin were administered together. In the third group, intra-peritoneal cisplatin and vitamin E were administered together. In the fourth group, intra-peritoneal cisplatin was administered together with curcumin in combination with vitamin E. In the fifth group, intra-peritoneal curcumin was administered alone. The sixth group was sacrificed directly without administration of any drugs. A distortion product otoacoustic emission (DPOAE) test was applied to both ears of all experimental animals. Curcumin was administered 1 h before cisplatin treatment continued for three successive days. Vitamin E was administered only as a single dose 30 min prior to cisplatin. All animals were sacrificed following DPOAE testing on the 5th day of cisplatin administration. Histopathological findings included a TUNEL (TdT-mediated deoxyuridine triphosphate nick end-labeling) assay, and the percentage of apoptotic cells was calculated. DPOAE values and the percentage of apoptotic cells were compared before and after treatment and between experimental groups. ResultsIn Group 1, DPOAE values were significantly decreased at all frequencies (3000 Hz, 4000 Hz and 6000 Hz; P < 0.05). In Groups 2, 3, 4 and 5 there was no significant difference between the pre- and post-treatment DPOAE results (p > 0.05). Apoptotic index values were lower in all treatment groups compared to the cisplatin group, however the difference was only statistically significant in group 3 (p = 0.009). ConclusionIn rats, cisplatin ototoxicity can be prevented with curcumin or curcumin-vitamin E combination.

Effects of ozone (O3) therapy on cisplatin-induced ototoxicity in rats.

The aim of this study is to investigate the effect of rectal ozone and intratympanic ozone therapy on cisplatin-induced ototoxicity in rats. Eighteen female Wistar albino rats were included in our study. External auditory canal and tympanic membrane examinations were normal in all rats. The rats were randomly divided into three groups. Initially, all the rats were tested with distortion product otoacoustic emissions (DPOAE), and emissions were measured normally. All rats were injected with 5-mg/kg/day cisplatin for 3days intraperitoneally. Ototoxicy had developed in all rats, as confirmed with DPOAE after 1week. Rectal and intratympanic ozone therapy group was Group 1. No treatment was administered for the rats in Group 2 as the control group. The rats in Group 3 were treated with rectal ozone. All the rats were tested with DPOAE under general anesthesia, and all were sacrificed for pathological examination 1week after ozone administration. Their cochleas were removed. The outer hair cell damage and stria vascularis damage were examined. In the statistical analysis conducted, a statistically significant difference between Group 1 and Group 2 was observed in all frequencies according to the DPOAE test. In addition, between Group 2 and Group 3, a statistically significant difference was observed in the DPOAE test. However, a statistically significant difference was not observed between Group 1 and Group 3 according to the DPOAE test. According to histopathological scoring, the outer hair cell damage score was statistically significantly high in Group 2 compared with Group 1. In addition, the outer hair cell damage score was also statistically significantly high in Group 2 compared with Group 3. Outer hair cell damage scores were low in Group 1 and Group 3, but there was no statistically significant difference between these groups. There was no statistically significant difference between the groups in terms of stria vascularis damage score examinations. Systemic ozone gas therapy is effective in the treatment of cell damage in cisplatin-induced ototoxicity. The intratympanic administration of ozone gas does not have any additional advantage over the rectal administration.

Protective effect of Pycnogenol on cisplatin-induced ototoxicity in rats

Context: Pycnogenol®, which is French maritime pine bark extract, is a potent antioxidant. It is used in medical conditions caused by oxidative stress. Cisplatin (cis-diamminedichloroplatinum II) is an antineoplastic agent. However, its serious side effects such as ototoxicity limit its usage.Objective: Antioxidants can be used to prevent ototoxicity. We investigated the effect of Pycnogenol® on cisplatin-induced ototoxicity.Materials and methods: Rats were randomly assigned to four groups of five. Distortion product-evoked otoacoustic emissions (DPOAE) test was performed for each rat. The experimental groups were as follows: Control Group, Pycnogenol® Group: 10 mg/kg Pycnogenol® intraperitoneally for 7 days, Cisplatin Group: intraperitoneally 15 mg/kg single injection of cisplatin on the fifth day, Cisplatin + Pycnogenol® Group: intraperitoneally 10 mg/kg Pycnogenol® treatment for 7 days, additionally on the fifth day, 15 mg/kg single injection of cisplatin was given. On the eighth day, DPOAE was re-performed and rats were sacrificed. Apoptosis was evaluated histopathologically.Results: Mean percentage of apoptotic cells was 1.5, 3, 30 and 11% in organ of Corti and 2, 2, 40, 15% in spiral ganglion neurons in Control Group, Pycnogenol® Group, Cisplatin Group and Cisplatin + Pycnogenol® Group, respectively. Cisplatin Group and Cisplatin + Pycnogenol® Group were significantly different when compared to Control Group histopathologically both in organ of Corti and spiral ganglion neuron (p <0.001, p = 0.019, p = 0.001, p = 0.015). DPOAE results showed that Cisplatin + Pycnogenol® Group was significantly different when compared to Cisplatin Group at 3, 6 and 8 kHz (p < 0.05).Conclusion: Pycnogenol protected against cisplatin ototoxicity. Also, pycnogenol is not ototoxic.

The effects of lycopene on cisplatin-induced ototoxicity

To investigate the potential preventive effect of lycopene in cisplatin-related ototoxicity. Thirty-five healthy 3-3.5-month adult female Sprague-Dawley rats were randomly divided into three groups and treated as follows: Group 1 (n = 10), received no cisplatin or lycopene. Both group 2 (n = 10) and; Group 3 (n = 15) received a single dose of 12 mg/kg cisplatin intraperitoneally. Lycopene was administered via gavage feeding in group 2 for 15 days. Prior to any medication administration, the baseline distortion product emissions were obtained in three groups. The animals were tested again at 15th day. The resulting distortion product otoacoustic emissions (DPOAE) were evaluated at 1.5, 2, 3, 4, 5, 6, 7, 8, 10, and 12 kHz. On day 0, prior to any medications, the initial DPOAEs measurement results gave similar values in the three groups (p > 0.05). In group 2 and 3, statistically significant differences were recorded for all frequencies between day 0 and day 15 values (p < 0.05). Lycopene group demonstrated significantly higher DP-grams except for 1.5 kHz frequency when compared to cisplatin group (p < 0.05). There was a statistically significant difference in basal and mid turn external ciliated cells number (p < 0.05), but there was no statistically significant difference in apical turn between three groups (p > 0.05). Stria vascularis changes were statistically significant between the groups, and the median score for stria vascularis injury was significantly greater in group 3 than in group 2 (p < 0.05). The median scores for spiral ganglion cells changes were significantly greater in group 3 than in group 2 (p < 0.05). The analyses of the results revealed statistically significant differences between two groups (p < 0.05), suggesting lycopene's possible protective effect against cisplatin ototoxicity. The present study revealed that administration of lycopene may demonstrate a protective role against cisplatin-induced ototoxicity in rats.

Protective effects of vitamins E, B and C andl-carnitine in the prevention of cisplatin-induced ototoxicity in rats

This experimental study aimed to investigate the effects of vitamins E, B and C and L-carnitine in preventing cisplatin-induced ototoxicity. Twenty-five adult, male, Wistar albino rats were randomly allocated to receive intraperitoneal cisplatin either alone or preceded by vitamins B, E or C or L-carnitine. Auditory brainstem response (i.e. hearing thresholds and wave I-IV intervals) and distortion product otoacoustic emissions (i.e. signal-to-noise ratios) were recorded before and 72 hours after cisplatin administration. The following statistically significant differences were seen: control group pre- vs post-treatment wave I-IV interval values (p < 0.05); control vs vitamin E and B groups' I-IV interval values (p < 0.05); control vs other groups' hearing thresholds; vitamin E vs vitamin B and C and L-carnitine groups' hearing thresholds (p < 0.05); and vitamin B vs vitamin C and L-carnitine groups' hearing thresholds (p < 0.05). Statistically significant decreases were seen when comparing the initial and final signal-to-noise ratios in the control, vitamin B and L-carnitine groups (2000 and 3000 Hz; p < 0.01), and the initial and final signal-to-noise ratios in the control group (at 4000 Hz; p < 0.01). Vitamins B, E and C and L-carnitine appear to reduce cisplatin-induced ototoxicity in rats. The use of such additional treatments to decrease cisplatin-induced ototoxicity in humans is still under discussion.