Vol 8, No 1 (2023)
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Audiometry and biochemical analysis in patients with tinnitus — preliminary findings

Stanisław Osiński1, Michał Osiński1, Daria Kupczyk2, Zofia Skubisz3, Beata Augustyńska4
Medical Research Journal 2023;8(1):35-40.

Abstract

Introduction: Tinnitus is a sound experience despite the lack of acoustic stimuli in the environment. This study aimed to report the audiometry and biochemical analysis of patients with tinnitus compared with the reference group.

Material and methods: The study included a total of 26 patients aged from 20 to 72 years with diagnosed idiopathic tinnitus and 19 healthy subjects as a control group. All patients underwent audiometric tone test, speech audiometry, distortion otoacoustic emissions product testing, the study of evoked auditory potentials of short latency, and biochemical analysis of venous blood concerning values of activity or concentration of the selected parameters of oxidative stress.

Results: Mean values of activity or concentration of the selected parameters of oxidative stress in the study and control groups showed reduced effectiveness of the body’s natural antioxidant barrier and intensification of treatment of lipid peroxidation. Discussion: There are a lot of factors suspected to generate tinnitus. A lot of them seem to be connected with biochemical disturbances inside the cochlea and in the central nervous system. It will be helpful to set such a battery of tests that contains the predictive indicators of tinnitus. It will be best if it is the battery of standard, not expensive tests of blood.

Conclusions: Proper levels of antioxidants may protect hearing. Glutathione and antioxidative enzymes may protect hearing organs against damage caused by free radicals. A lower level of the antioxidants and associated intensification of lipids peroxidation processes may increase free radicals-associated damage and lead to hearing organ dysfunction.

ORIGINAL ARTICLE

Medical Research Journal 2023;

Volume 8, Number 1, 35–40

10.5603/MRJ.a2023.0005

Copyright © 2023 Via Medica

ISSN 2451-2591

e-ISSN 2451-4101

Audiometry and biochemical analysis in patients with tinnitus — preliminary findings

Stanisław Osiński1Michał Osiński1Daria Kupczyk2Zofia Skubisz3Beata Augustyńska4
1Department of Otorhinolaryngology, Provincial Specialist Hospital in Slupsk, Poland
2Department of Medical Biology and Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland
3Student of Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland
4Institute of Physical Education, Kazimierz Wielki University in Bydgoszcz, Poland

Corresponding author:

Beata Augustyńska, Institute of Physical Education, Kazimierz Wielki University in Bydgoszcz, Poland; e-mail: augustynska@op.pl

Abstract

Introduction: Tinnitus is a sound experience despite the lack of acoustic stimuli in the environment. This study aimed to report the audiometry and biochemical analysis of patients with tinnitus compared with the reference group.

Material and methods: The study included a total of 26 patients aged from 20 to 72 years with diagnosed idiopathic tinnitus and 19 healthy subjects as a control group. All patients underwent audiometric tone test, speech audiometry, distortion otoacoustic emissions product testing, the study of evoked auditory potentials of short latency, and biochemical analysis of venous blood concerning values of activity or concentration of the selected parameters of oxidative stress.

Results: Mean values of activity or concentration of the selected parameters of oxidative stress in the study and control groups showed reduced effectiveness of the body’s natural antioxidant barrier and intensification of treatment of lipid peroxidation. Discussion: There are a lot of factors suspected to generate tinnitus. A lot of them seem to be connected with biochemical disturbances inside the cochlea and in the central nervous system. It will be helpful to set such a battery of tests that contains the predictive indicators of tinnitus. It will be best if it is the battery of standard, not expensive tests of blood.

Conclusions: Proper levels of antioxidants may protect hearing. Glutathione and antioxidative enzymes may protect hearing organs against damage caused by free radicals. A lower level of the antioxidants and associated intensification of lipids peroxidation processes may increase free radicals-associated damage and lead to hearing organ dysfunction.

Key words: tinnitus, oxidative stress, antioxidant barrier, hearing, audiometry

Med Res J 2023; 8 (1): 35–40

Introduction

Tinnitus is a sound experience despite the lack of acoustic stimuli in the environment. The relationship between hearing deficits and tinnitus is not clear. A few chronic tinnitus patients show normal hearing thresholds in the pure tone audiometry from 125 Hz to 8000 Hz (≤ 20 dB) [1–5]. Such heterogeneity of tinnitus constitutes a major challenge for clinical studies the aetiology of tinnitus covers the complex interaction of many factors.

This study aimed to report the audiometry and biochemical analysis, with particular emphasis on selected parameters of oxidative stress, of those patients with tinnitus compared with the reference group.

Material and methods

The study included a total of 26 patients aged from 20 to 72 years (mean age: 54.19 years) with tinnitus, who were diagnosed with tinnitus in the Department of Otolaryngology and Otolaryngological Oncology Unit with the Subunit of Audiology and Phoniatrics of Nicolaus Copernicus University Collegium Medicum in Bydgoszcz.

The control group consisted of 19 healthy subjects (recruited among acquaintances) aged 20 to 60 years (mean age 49.2), who were not complaining of any audiological problems, well communicating by hearing, not receiving any chronic medication (Tab. 1).

Table 1. Patients overall profile

Study group

n = 26 (100%)

Reference group

n = 19 (100%)

Age [years]:

Min

Max

Mean

20

72

54.19

20

60

49.2

Gender:

F

M

14 (53.85%)

12 (46.15%)

10 (52.63%)

9 (47.37%)

The results of anamnesis and tinnitus effect on the ability for speech understanding are summarized in Table 2.

Mean hearing loss in the study patients on tonal audiometry was: 30,6dB (SD = 24, 81, median 25) in the left ear and 44,8 dB (SD = 27, 82, median 38, 57) in the right ear, taking into consideration frequencies from 125 to 8000Hz.

All patients underwent the tone audiometric test (audiometer Interacoustic), speech audiometry (audiometer Interacoustic), distortion otoacoustic emissions product testing (camera Madsen) and the study of evoked auditory potentials of short latency BERA (camera Synapsys).

Table 2. Tinnitus characteristics and influence on speech understanding

Min

Max

Mean

SD

Median

Q1

Q2

Intensity

10

110

58.2

22,54

60

40

75

Frequency

500

8000

3370

1869,6

4000

2000

4000

Localization

L: 12 patients (46,15%), R: 8 patients (13,77%), L,R 6 patients (23.08%)

Annoyance

2

10

6.69

2.24

7

5.25

8

Psychological effect

Concentration: 15 patients (57.69%), irritability: 7 patients (26.92%), sleep: 3 patients (11.54), heaviness: 1 patient (3.85)

Camouflage

Present: 9 patients (40.9%), absent: 13 patients (59.1%)

Time characteristics

Continuous: 20 patients (76.92%), throbbing: 6 patients (23.08%)

Speech audiometry (R ear)

Threshold of distinction

20

80

33.57

17.33

30

20

40

Level of distinction

100% has 100%

Speech audiometry (L ear)

Threshold of distinction

10

90

45.71

26.23

40

25

70

Level of distinction

100% has 100%

Material

The material for analysis was venous blood collected in an amount of approx. 8 ml of the antecubital vein into lithium heparin tubes and tubes without anticoagulant. Blood samples were collected at 8.00. Then, the collected material was transported to the Department of Biochemistry of Nicolaus Copernicus University Collegium Medicum in Bydgoszcz. Tests were carried out on the same day, within approx. 1 hour of material collection. Based on own studies, no statistically significant differences in haematocrit between the study and the control group were noted. From the blood drawn into tubes without anticoagulant (approx. 3 ml) serum was obtained by centrifugation of the material over 5 min at 5000 × g, then it was transferred to Eppendorf tubes and frozen at –80°C. The prepared serum was stored to determine the activity of the oxidase ceruloplasmin (Cp). Before preparing the haemolysate, 500μl blood was collected to determine the levels of glutathione (GSH) in the erythrocytes, the remaining aliquot of blood (approx. 5 ml) was centrifuged to obtain plasma, wherein the concentration of nitrate/nitrite was determined. The remaining cells were used for the preparation of the haemolysate, wherein the dialdehyde malonic concentration (MDA) and the activity of the enzymes: glutathione peroxidase (cGPx), glutathione S-transferase (GST) and superoxide dismutase (SOD-1) were determined.

Table 3. Biochemical parameters (study group)

Min

Max

Mean

SD

Median

Q1

Q2

HT

33.5

49

41.49

3.19

42

40.25

43

GSH

2.05

3.2

2.58

0.29

2.5

2.36

2.79

GPXOS

172.7

290.3

218.97

29.19

212.1

199.05

240.13

GPXRBC

9.6

18.7

14.33

2.55

14.35

12.89

15.7

GSTRB

2.3

4.4

3.23

0.55

3.1

2.8

3.58

GRRBC1

42

82.8

54.6

10.28

51.7

47.8

58.85

SODRBC1

2050

2770

2411.92

190.07

2380

2312.5

2552.5

MDARBC1

0.23

0.32

0.28

0.02

0.28

0.26

0.29

Nitrates/nitrites

0.46

2.01

1.14

0.42

1.08

0.88

1.44

CP

555.2

1837.6

1078.31

303.89

1008.65

855.95

1192.43

CRP

0.41

6.72

1.67

1.57

0.99

0.58

2.22

Cholesterol

87

345

201.35

58.7

203

161.25

240.25

HDL

36

88

55.31

14.39

52

47.25

61.75

LDL

36

245

125.29

48.36

127

92

150.5

TG

43

248

116.96

49.23

112

82

147.25

Statistical analysis

Where available mean, median, minimum value (Min), maximum value (Max) and standard deviation (SD) were calculated to show the results of this study. The Shapiro-Wilk test was used as a powerful normality test. Parametric t-student test and non-parametric Wilcoxon’s test were used to compare scores. Spearman’s Rho was used to assess correlations.

All the data in this study were collected and stored using the MS Access 2013 software. Statistical analysis was performed using IBM SPSS Statistics.

The difference was statistically significant at p < 0.05.

Table 4. Biochemical parameters (reference group)

Min

Max

Mean

SD

Median

Q1

Q3

HT

36

48

43.34

3.25

43.75

41.5

45.75

GSH

2

2.6

2.21

0.16

2.175

2.1

2.3

GPXOS

164.2

379.3

246.05

48.29

227.85

220.45

261.55

GPXRBC

14.8

22.2

18.91

2.26

19.4

17.65

20.15

GSTRB

1.7

3.3

2.49

0.42

2.65

2.25

2.7

GRRBC1

37

86

55.15

11.21

54.05

48.75

58.3

SODRBC1

2500

3090

2805.26

184.77

2897.5

2670

2950

MDARBC1

0.19

0.3

0.25

0.03

0.26

0.22

0.28

Nitrates/nitrites

0.09

2.79

0.81

0.63

0.635

0.39

1.03

CP

563.2

2559.4

1340.358

542.45

1271.75

1039.05

1343.15

Ethics

This study was conducted following the Declaration of Helsinki and the guidelines for Good Clinical Practice (GCP). Freely given written informed consent was obtained from every patient before the study.

Results

No statistically relevant differences between females and males were observed. No statistically relevant differences between younger and older patients were observed (Tab. 37).

Table 5. Correlations part I (study group)

HT

GSH

GPXOS

GPXRBC

GSTRB

GRRBC1

SODRBC1

MDARBC1

Nitrates//nitrites

CP

HT

Ns

Ns

Ns

Ns

Ns

Ns

Ns

–0.432

p = 0.028

Ns

GSH

Ns

Ns

Ns

0.401

p = 0.042

Ns

Ns

0.39

p = 0.049

Ns

GPXOS

Ns

Ns

Ns

Ns

Ns

Ns

Ns

GPXRBC

Ns

Ns

Ns

Ns

Ns

Ns

GSTRB

Ns

Ns

Ns

0.537

p = 0.004

Ns

GRRBC1

Ns

Ns

Ns

Ns

SODRBC1

Ns

Ns

Ns

MDARBC1

Ns

Ns

Nitrates/nitrites

Ns

CP

Table 6. Correlations part II (study group)

CRP

Cholesterol

HDL

LDL

TG

CRP

Ns

Ns

Ns

Ns

Cholesterol

0.452

p = 0.02

0.673

p = 0.000

0.467

p = 0.016

HDL

0.414

p = 0.035

Ns

LDL

Ns

TG

Table 7. Correlations (reference group)

HT

GSH

GPXOS

GPXRBC

GSTRB

GRRBC1

SODRBC1

MDARBC1

Nitrates//nitrites

CP

HT

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

GSH

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

GPXOS

Ns

Ns

Ns

Ns

Ns

Ns

Ns

GPXRBC

Ns

Ns

Ns

Ns

Ns

GSTRB

-

Ns

Ns

Ns

Ns

Ns

GRRBC1

–0.587

p = 0.008

0.523

p = 0.022

0.679

p = 0.001

Ns

SODRBC1

Ns

-0.596

p = 0.007

Ns

MDARBC1

0.557

p = 0.013

Ns

Nitrates/nitrites

Ns

CP

Moderate correlations observed in the study group were not observed in the reference group. It may suggest that the distribution of parameters in the study group may reflect the influence of tinnitus (Tab. 8).

Table 8. Correlations (study group)

HT

GSH

GPXOS

GPXRBC

GSTRB

GRRBC1

SODRBC1

MDARBC1

Nitrates//nitrites

CP

Intensity

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Frequency

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Annoyance

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

Ns

CR

Cholesterol

HDL

LDL

TG

Intensity

Ns

Ns

Ns

Ns

Ns

Frequency

–0.506

p = 0.016

Ns

Ns

Ns

Ns

Annoyance

Ns

Ns

Ns

Ns

Ns

Discussion

Individual or coexisting cochlear (attributed to cochlear impairment) and neural (altered neural firing within the auditory pathway) mechanisms of tinnitus generation may influence auditory temporal resolution in tinnitus patients even with normal audiometry [2]. The general model of changed hearing thresholds in patients with tinnitus was proposed by Gollnast et al. [4]. Neuronal noise (described by Faisal) may induce changes in the auditory pathway. Many factors such as different age groups and different tinnitus pitches may diminish the results of previous studies [4].

Young patients with tinnitus usually show lower hearing thresholds compared to healthy people of the same age. In adult patients with tinnitus differences may be more heterogeneous: hearing thresholds in patients with tinnitus are lower in low-frequency ranges, while they are higher at high frequencies [4] Transient evoked otoacoustic emissions (TEOAE) and ultra-high frequency (UHF) hearing thresholds may be severely influenced in patients with tinnitus: TEOAE are abnormal in 72.2% of the tinnitus patients, and 18.2% of the control group and UHF thresholds are poorer [5].

There are a lot of factors suspected to generate tinnitus. A lot of them seem to be connected with biochemical disturbances inside the cochlea and in the central nervous system and cause oxidative processes with the activation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [6, 7]. It will be helpful to set up a set of tests that contains the predictive indicators of tinnitus. It will be best if it is a set of inexpensive blood tests. Direct measurement of oxidative stress may reflect changes in hearing disorders [8]. The aforementioned disorders may be caused by exposition to high-intensity of noise and/or vibrations, the influence of drugs (chemotherapeutics, antibiotics, etc.) resulting in damage of hearing organ structures, loss of hearing, tinnitus or balance disturbances [9–11]. In addition, there is a decrease in the level of antioxidants, which may result in the intensification of lipid peroxidation processes and a decrease in glutathione levels [12–14]. Celik et al. in their studies indicate that the development of oxidative stress and the imbalance of antioxidant enzymes concerns a group of patients with tinnitus [15]. Also, in the authors’ other studies, a decrease in the activity of antioxidant enzymes and an intensification of lipid peroxidation processes were observed in patients with tinnitus compared to the control group. A study by Diao et al. showed that exposition to high-intensity noise may cause to decrease in antioxidative ability in serum and an increase of nitrates in guinea pigs [16], resulting in the generation of toxic peroxynitrite. Increased level of nitrates was observed in patients with tinnitus [17, 18]. Also, in the present study, higher levels of nitrates were observed in the group of patients with tinnitus compared to the control group. An increase in nitric oxide levels may underlie the pathogenesis of tinnitus [18]. Own results showed a correlation between the level of glutathione and the level of nitrates/nitrites. Human glutathione transferase catalyses the formation of S-nitroso glutathione from organic nitrites and glutathione [19]. Increased activity of this enzyme was observed in the present study in patients with tinnitus compared to the control group. In addition, the increase in glutathione levels together with the increase in nitrates supports the protective role of glutathione against the action of free radicals. Also, Koç et al. showed a decrease in antioxidant ability in patients with tinnitus compared with the reference group [20]. Moreover, high-intensity of vibrations may cause hearing damage [21, 22]. Other authors explain the background of idiopathic tinnitus with endothelium dysfunctions and damages of microcirculation within cochlea: the aforementioned situation may intensify processes of lipids peroxidation as far as the increase of concentration of MPO, 4-hydroksynonenal, nitrates or L-arginine [17, 23, 24]. Oxidative processes may lead to disorders of biomechanical paths and tinnitus [25, 26]. Glutathione and antioxidative enzymes may protect hearing organs against damage caused by free radicals. The participation of reactive oxygen species in the development of oxidative stress results in neurootological disorders and may affect the etiopathogenesis of tinnitus.

Tinnitus diagnostics allows for the selection of the treatment method. At least several main ways of treatment are possible, thus key role plays the precise and objective location of the problem. The main indication to research the functioning of the antioxidant barrier in people suffering from ailments in the form of tinnitus is to determine a suitable therapy aimed at improving the quality of life of these patients, which might be the administration of antioxidant medications. Neurorehabilitation also offers many options: from transcranial magnetic stimulation (TMS) to methods such as McKenzie, OMI Cyriax, etc.

There is a need for further, more detailed studies on bigger samples. Temporal resolution testing in patients with tinnitus may significantly improve diagnosis and therapy [2]. Data-driven categorization of hearing function seems to be a promising approach for profiling tinnitus patients [3].

Further outcomes of the present study will be reported in a more detailed report.

Conclusions

The proper level of antioxidants may protect hearing. A lower level of the antioxidants and associated intensification of lipids peroxidation processes may increase free radicals-associated damage and lead to hearing organ dysfunction.

Conflict of interests: None.
Funding: None.

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