The Effect of the Intra-Arterial Heparin Flushing (IAHF) Procedure on Hearing Threshold in Sensorineural Hearing Loss Patients.

Background: Sensorineural hearing loss (SNHL) is a frequent problem in Indonesia but its treatment is still limited. This type of hearing loss is related to oxidative stress and decreased vascularization, which can damage the hair cell. The intra-arterial heparin flushing (IAHF) is a procedure that can recover circulation and its agent, namely heparin, also has antioxidant activity. Therefore, the IAHF procedure has the potential to improve hearing function and can be considered an alternative therapy for SNHL. Objective: The study evaluates the effect of the IAHF on hearing improvement based on the difference in hearing threshold values before and after the procedure. Methods: This experimental study used a Pretest-Posttest One-Group Only design. A total of 17 patients with sensorineural hearing loss who met inclusion and exclusion criteria were subjected to pure tone audiometry tests before and 4 hours after the IAHF procedure. The mean difference in hearing threshold was analyzed using paired Students t-test for normally distributed data and Wilcoxon for non-normally distributed data. Results: There was a decrease in the means of hearing threshold in the right and left ear 4 hours after the IAHF procedure. However, based on the paired Students t-test, there was not a significant difference in hearing threshold before and after the procedure (p-value > 0.05). Conclusion: There was hearing threshold improvement 4 hours after the IAHF procedure. This study showed that the IAHF procedure can have a therapeutic effect on sensorineural hearing loss patients.

Curcumin Prevents Ototoxicity Induced by Cisplatin as Evaluated with OAE.

Introduction: This study, assess the efficacy of curcumin therapy in preventing/improving cochlear damage in Rattus norvegicus ototoxic model as evaluated with OAE examination. Materials and Methods: This study utilized 27 rats which had been injected with single dose 8mg/KgBB of cisplatin, and then divided into 3 groups. The first group was not given curcumin. The second group received curcumin at a dose of 150 mg/KgBB. The third group received curcumin at a dose of 300 mg/KgBB. Curcumin was given from the time of single dose cisplatin injection (day 0) to day 7. OAE examination was performed on the day before the single dose of cisplatin (day 0), day 3, 4 and 7 after curcumin administration. Results: There was a decline in the average value of SNR in all groups starting from high frequency. However, in the rat groups receiving curcumin there was a slow decrease in the SNR value, which also obtained statistically significant differences in the SNR values of all groups. Conclusion: Administration of certain doses of curcumin may reduce the modest and statistically insignificant decrease in mean SNR values indicating a reduction in ototoxicity from cisplatin.

Correlation between signal transducer and activator of transcription 1 (STAT 1), vascular endothelial growth factor (VEGF), and signal to noise ratio (SNR) value in otoacoustic emission (OAE) examination on organ of Corti cochlea due to cisplatin.

Aim To assess the cochlear damage caused by cisplatin in the rat cochlea based on decreased signal to noise ratio (SNR) values on otoacoustic emission (OAE) examination and increased expression of signal transducer and activator of transcription 1 (STAT 1) and vascular endothelial growth factor (VEGF) on immunohistochemical examination. Methods Twenty-four Rattus norvegicus were divided into 4 groups and injected with 8 mg/kgBW of cisplatin intraperitoneally except for control group. The SNR on OAE examination were checked before the treatment and on day 3, 4, and 7 after the treatment. The cochleas were stained immunohistochemically, followed by assessment of the cochlear organ of Corti damage based on STAT 1 and VEGF expression. Results A decrease in the mean of SNR value was found in accordance with the length of cisplatin exposure. The STAT 1 and VEGF expression increased with duration of cisplatin exposure. A correlation was found between SNR values, STAT 1, and also VEGF expression (p<0.05). Conclusion An increase of STAT 1 and VEGF expression influences cochlear damage due to cisplatin administration. There was a correlation between STAT 1 and VEGF expression with SNR values in the cochlear organ of Corti of Rattus norvegicus exposed to cisplatin.

The Correlation of Signal to Noise Ratio Value on DPOAE with Malondialdehyde Levels in Rattus Norvegicus Diabetes Model.

Introduction: The aim of this study was to determine the correlation of the signal-to-noise ratio (SNR) value on distortion product otoacoustic emissions (DPOAE) examination with malondialdehyde (MDA) levels in a diabetic rat model. Materials and Methods: The subjects of this study were 25 rats. The samples were divided into 5 groups (days of confirmed diabetes): group 1 (control/non-treatment); group 2 (3 days); group 3 (6 days); group 4 (9 days); and group 5 (12 days). Samples that confirmed diabetes were assessed by DPOAE examination and subjected to MDA-level examination. The data were processed using SPSS and considered significant if p <0.05. Results: The study showed a decrease in SNR values and an increase in MDA levels for the rats, which was confirmed by diabetes. The most significant result was shown by group 5, which compared to the other diabetes groups. A post hoc test showed the significant difference SNR value in each group (p<0.05); except for groups 1 and 2, the MDA levels showed significant differences for all groups. The Pearson correlation test showed a negative correlation between SNR values and MDA levels. A significant correlation between SNR values and MDA levels was found in group 5. Conclusions: The study showed a correlation of SNR values from DPOAE examination to MDA levels in diabetes rats, indicating that there has been tissue damage (cochlea), which is characterized by a decrease in the SNR value.

Antioxidant Effect of Curcumin on the Prevention of Oxidative Damage to the Cochlea in an Ototoxic Rat Model Based on Malondialdehyde Expression

Abstract Introduction Aminoglycoside, as an antimicrobial medication, also has side-effects on the inner ears, bringing about hearing disorders. Curcumin has been proven to be a strong scavenger against various reactive oxygen species (ROS), and the increase in ROS production is considered to play an important role in the process of hearing disorder. Objective To prove that curcumin is an effective antioxidant to prevent cochlear damage based on malondialdehyde (MDA) expression. Methods The present research used 32 Rattus norvegicus, of the Wistar lineage, randomly divided into 8 groups: negative control, ototoxic control (a single dose of 40 mg/ml of gentamicin via intratympanic injection), 2 groups submitted to ototoxic control + curcumin treatment (100 mg/kg, 200 mg/kg), 2 groups who iunderwent ototoxic control + curcumin treatment for 7 days, and two groups submitted to curcumin treatment as prevention for 3 days + ototoxic induction. Results The results showed that the lowest dosage of curcumin (100 mg/kg) could decrease MDA expression on the cochlear fibroblastic wall of the ototoxic model; however using greater doses of curcumin (200 mg/kg) for 7 days would provide a better effect. Curcumin could also significantly decrease MDA expression when it was administered during the preototoxic exposure. Conclusion Curcumin can be used as a therapy for ototoxic prevention based on the decrease in MDA expression.

Antioxidant Effect of Curcumin on the Prevention of Oxidative Damage to the Cochlea in an Ototoxic Rat Model Based on Malondialdehyde Expression.

Introduction Aminoglycoside, as an antimicrobial medication, also has side-effects on the inner ears, bringing about hearing disorders. Curcumin has been proven to be a strong scavenger against various reactive oxygen species (ROS), and the increase in ROS production is considered to play an important role in the process of hearing disorder. Objective To prove that curcumin is an effective antioxidant to prevent cochlear damage based on malondialdehyde (MDA) expression. Methods The present research used 32 Rattus norvegicus , of the Wistar lineage, randomly divided into 8 groups: negative control, ototoxic control (a single dose of 40 mg/ml of gentamicin via intratympanic injection), 2 groups submitted to ototoxic control + curcumin treatment (100 mg/kg, 200 mg/kg), 2 groups who iunderwent ototoxic control + curcumin treatment for 7 days, and two groups submitted to curcumin treatment as prevention for 3 days + ototoxic induction. Results The results showed that the lowest dosage of curcumin (100 mg/kg) could decrease MDA expression on the cochlear fibroblastic wall of the ototoxic model; however using greater doses of curcumin (200 mg/kg) for 7 days would provide a better effect. Curcumin could also significantly decrease MDA expression when it was administered during the preototoxic exposure. Conclusion Curcumin can be used as a therapy for ototoxic prevention based on the decrease in MDA expression.

Correlation of SOD and MDA Expression in the Organ of Corti and Changes in the Function of Outer Hair Cells Measured by DPOAE Examination in Noise-Exposed Rat Cochlea.

BACKGROUND: Hearing loss due to noise can cause the disturbances toward the quality of life and cause mechanical damage and metabolic decompensation. Distortion Product Otoacoustic Emission (DPOAE) is an examination to assess the sensory function of outer hair cells. Superoxide Dismutase (SOD) and Malondialdehyde (MDA) are markers of oxidative stress. The aim of this study was to identify the correlation between DPOAE examination and SOD and MDA expression in rats exposed to noise. METHODS: This research was conducted on 27 rats which were divided into 3 groups, group 1 (control), group 2, and group 3 were groups with 100 dB and 110 dB noise exposure respectively. RESULTS: Our findings show a decrease in SOD expression and DPOAE values as well as an increase in MDA expression in rats exposed to noise and there is a positive correlation between Signal to Noise Ratio (SNR) value with SOD expression (r= 0.733, p= 0.025) and a negative correlation between SNR value with MDA expression (r= -0.678, p= 0.045). CONCLUSION: our study find the correlation of oxidant and antioxidant status values in the organ of corti and changes in the function of outer hair cells in noise-exposed rat models.

The Benefits of Curcuminoid to Expression Nuclear Factor Erythroid 2 Related Factor 2 (NRF2) and Signal to Noise Ratio (SNR) Value in the Noise Exposed Organ of Corti of Rattus Norvegicus.

BACKGROUND: Noise-induced hearing loss (NIHL) can cause damage to the cochlea. Curcumin and nuclear factor erythroid 2-related factor 2 (NRF2) are transcription activators that play a crucial role in defence mechanisms against oxidative stress. The aim of this study was to determine the effect of curcuminoid administration on NRF2 expression, in the organ of Corti of cochlea of Rattus norvegicus that were exposed to noise, from the results of the distortion product otoacoustic emission (DPOAE) examination. METHODS: We divided 36 rats into six groups including Group 1 (control); Group 2 (noise exposure without curcuminoid administration); Group 3 (noise exposure+curcuminoid dose 100 mg/day for four days); Group 4 (noise exposure+curcuminoid dose 200 mg/day for four days); Group 5 (curcuminoid dose of 100 mg/day for 14 days followed by two days of noise exposure); Group 6 (curcuminoid dose 200 mg/day for 14 days followed by two days of noise exposure). RESULTS: Following noise exposure in rats, there was an effect/correlation between NRF2 expression, the SNR values obtained from DPOAE and curcuminoid administration. CONCLUSION: There was a correlation between curcuminoid administration, NRF2 expression and DPOAE treatment. Following noise exposure in rats (Rattus norvegicus), SNR values obtained from DPOAE showed improved cochlear function.

Elevated matrix metalloproteinase-3 level may affect hearing function in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease. Sensorineural and conductive hearing loss have been reported in RA, but the results of most studies are not in agreement. The pathogenesis of the hearing loss is not clearly understood. The presence of sensorineural hearing loss was related to matrix metalloproteinase-3 (MMP-3). The aim of this study was to assess hearing loss in RA patients and to examine the correlation between plasma MMP-3 levels and hearing loss in such patients. METHODS: This is a cross-sectional and analytic research. Subjects consisted of 21 RA patients with hearing loss as a study group and 21 RA patients without hearing loss as controls. All patients were evaluated by pure tone audiometry and tympanometry. The amounts of plasma MMP-3 were determined using enzyme-linked immunosorbent assay. Pearson Chi-square test was used to determine the correlation of gender, age, disease duration, erythrocyte sedimentation rate, and platelet count of both groups. Independent t-test was used to assess equality of mean values at 250 to 8000 Hz hearing thresholds, pure tone mean values, air-bone gaps, and MMP-3 plasma levels of both groups. RESULTS: This study found sensorineural (76.2%), conductive (14.3%), and mixed (9.5%) hearing loss. The most common degree of hearing loss was mild (66.7%). There was an increased incidence of As-type tympanogram in the study group (28.6%) and control group (47.6%). There were significant differences between both groups in mean hearing thresholds (p < 0.001), mean of air conduction thresholds at 1000 to 8000 Hz (p < 0.05), and mean of bone conduction thresholds in all frequencies (p < 0.05). The significant difference of mean MMP-3 levels was also found between the groups (p < 0.001). CONCLUSION: Hearing loss is a common finding in RA. MMP-3 plasma contributed to degrade the incudomalleolar and incudostapedial joints and could damage the inner ear hair cells due to oxidative process in RA.

Decreased Protein Kinase C Expression in the Cochlear Fibroblasts of Diabetic Rat Models Induced by Curcumin.

OBJECTIVES: Microcirculation and hemodynamic disturbances, including in the cochlea, are commonly found in diabetic patients. A study on diabetic rats discovered histopathological changes in outer hair cells and the spiral ganglion and mitochondrial damage in the ear. Hyperglycemia can increase the activation of protein kinase C (PKC). Curcumin as an antioxidant also affects the regulation of PKC and Ca2+. The aim of this study was to determine the role of curcumin in decreasing PKC expression in the cochlear fibroblasts of diabetic rats. MATERIALS AND METHODS: An experimental study was performed on 24 Wistar rats divided into the following 6 groups: group 1: control group; group 2: diabetic group without curcumin administration; groups 3 and 4: diabetic groups with curcumin administration (200 mg/kg and 400 mg/kg for 3 days, respectively); groups 5 and 6: diabetic groups with curcumin administration (200 mg/kg and 400 mg/kg for 8 days, respectively). Cochlear tissues were taken from all groups and immunohistochemistry-stained, and the PKC expression scores were analyzed with one-way ANOVA (a significance level of 0.05). RESULTS: Significant differences in PKC expression (p<0.05) were found between group 1 and group 2, and group 2 and groups 3, 4, 5, and 6. There was no significant difference in PKC expression regarding the different doses and the duration of curcumin administration. CONCLUSION: Curcumin can reduce PKC expression in the cochlear fibroblasts of diabetic rats.

The Antiapoptotic Effect of Curcumin in the Fibroblast of the Cochlea in an Ototoxic Rat Model.

INTRODUCTION: This study aimed to show the potency of curcumin as an antiapoptotic agent that decreases the apoptotic index in the cochlea lateral wall in ototoxic rat models. MATERIALS AND METHODS: A total of 24 Rattus norvegicus were divided into eight groups: Group 1 (control group), Group 2 (gentamicin (+)), Group 3 (gentamicin + curcumin 20 mg/day), Group 4 (gentamicin + curcumin 40 mg/day), Group 5 (gentamicin + curcumin 20 mg/day for 7 days), Group 6 (gentamicin + curcumin 40 mg/day for 7 days), Group 7 (curcumin 20 mg/day for 3 days + gentamicin), and Group 8 (curcumin 40 mg/day for 3 days + gentamicin). After the division, the rats were terminated in order to measure the apoptotic index using a terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay in the fibroblasts of the cochlea lateral walls. The data were analyzed using analysis of variance (ANOVA), and P<0.05 was used as the cut-off for statistical significance. RESULTS: Administration of gentamicin showed significant differences (P<0.05) in the apoptotic index. Groups undergoing curcumin treatment at a higher dose (200 mg/kg bw) and the prevention groups showed significant differences compared with groups not treated with curcumin. CONCLUSION: This study concluded that the apoptotic index can be decreased by curcumin and has a preventive benefit toward ototoxic rat models. The administration of curcumin depended on the dose and duration.

The Antioxidant Effect of Curcumin on Cochlear Fibroblasts in Rat Models of Diabetes Mellitus.

INTRODUCTION: The aim of this study was to investigate the potential of curcumin as an antioxidant to increase the expression of superoxide dismutase (SOD) in fibroblasts of the cochlear lateral wall in rat models of diabetes mellitus. MATERIALS AND METHODS: Twenty-four male Wistar rats Rattus norvegicus were randomly divided into six groups: group 1 as the control group; group 2 as the diabetic group; group 3 and 4 as the diabetic groups that received curcumin therapy of 200 and 400 mg/kg b.w. for 3 days, respectively; and group 5 and 6 as the diabetic groups that received curcumin therapy of 200 and 400 mg/kg b.w. for 8 days, respectively. All rats underwent termination and necropsy procedure on their temporal bones for immunohistochemical assay to determine the expression of SOD. RESULTS: The decreased expression of SOD was detected in the diabetic group (without curcumin treatment). The treatment of curcumin at doses of 200 and 400 mg/kg b.w. for 3 and 8 days led to significant differences (P<0.05) in the expression of the SOD compared to diabetic group (without curcumin treatment). No significant differences were found in terms of dose and duration of curcumin administration on the expression of SOD. CONCLUSION: Curcumin may act as an antioxidant against oxidative stress due to diabetes mellitus via increased expression of SOD on cochlear fibroblasts in rat models of diabetes mellitus.

Curcumin Reduces the Noise-Exposed Cochlear Fibroblasts Apoptosis

Abstract Introduction The structural changes underlying permanent noise-induced hearing loss (NIHL) include loss of the sensory hair cells, damage to their stereocilia, and supporting tissues within the cochlear lateral wall. Objective The objective of this study is to demonstrate curcumin as a safe and effective therapeutic agent in the prevention and treatment for fibroblasts damage within the cochlear supporting tissues and lateral wall through cell death pathway. Methods We divided 24 Rattus norvegicus into 4 groups, Group 1: control; Group 2: noise (þ); Group 3: noise (þ), 50 mg/day curcumin (þ); Group 4: noise (þ), 100 mg/day curcumin (þ). We provided the noise exposure dose at 100 dB SPL for two hours over two weeks and administered the curcumin orally over two weeks. We examined all samples for the expressions of calcineurin, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and apoptotic index of cochlear fibroblasts. Results We found significant differences for the expressions of calcineurin (p< 0.05) in all groups, significant differences for the expressions of NFATc1 (p< 0.05) in all groups, except in Groups 1 and 4, and significant differences for the apoptotic index (p< 0.05) in all groups. Conclusion Curcumin proved to be potentially effective in the prevention and treatment for fibroblasts damage within the cochlear supporting tissues and lateral wall regarding the decreased expression of calcineurin, NFATc1, and apoptotic index of cochlear fibroblasts.

Curcumin Reduces the Noise-Exposed Cochlear Fibroblasts Apoptosis.

Introduction The structural changes underlying permanent noise-induced hearing loss (NIHL) include loss of the sensory hair cells, damage to their stereocilia, and supporting tissues within the cochlear lateral wall. Objective The objective of this study is to demonstrate curcumin as a safe and effective therapeutic agent in the prevention and treatment for fibroblasts damage within the cochlear supporting tissues and lateral wall through cell death pathway. Methods We divided 24 Rattus norvegicus into 4 groups, Group 1: control; Group 2: noise (+); Group 3: noise (+), 50 mg/day curcumin (+); Group 4: noise (+), 100 mg/day curcumin (+). We provided the noise exposure dose at 100 dB SPL for two hours over two weeks and administered the curcumin orally over two weeks. We examined all samples for the expressions of calcineurin, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and apoptotic index of cochlear fibroblasts. Results We found significant differences for the expressions of calcineurin (p < 0.05) in all groups, significant differences for the expressions of NFATc1 (p < 0.05) in all groups, except in Groups 1 and 4, and significant differences for the apoptotic index (p < 0.05) in all groups. Conclusion Curcumin proved to be potentially effective in the prevention and treatment for fibroblasts damage within the cochlear supporting tissues and lateral wall regarding the decreased expression of calcineurin, NFATc1, and apoptotic index of cochlear fibroblasts.