**1.1 Characteristic: glucocorticoids**

The adrenal cortex synthesizes two classes of steroids: corticosteroids (mineralocorticoids and glucocorticoids) and androgens. One of the differences is the number of carbon atoms. Corticosteroids have 21 carbon atoms, and androgens have 19 carbon atoms. In the human body, the main glucocorticoid is cortisol, and the main mineralocorticoid is aldosterone [5].

Glucocorticoid receptor (GR) is located in the cytoplasm in inactive form until it binds with the molecule of glucocorticoid. This action results in activation of receptor and translocation complex: *glucocorticoid receptor for glucocorticoid* to the nucleus. Activation of receptor is based on dissociation from the associated proteins. After translocation to the nucleus, a complex of glucocorticoid receptor interacts with specific, short DNA sequences with the regulatory regions. The regions are termed *glucocorticoid responsive elements* (GREs) and allow induction of the gene transcription by glucocorticoids. This process is very complicated because of interaction with specific cofactors and proteins and still not well and completely understood by scientists and researchers [5]. Not only positive response to glucocorticoid is possible. According to Webster and Cidlowski, genes negatively regulated by glucocorticoids were also identified [6]. An example of downregulation (negative regulation) is to repress the expression of gene responsible for encoding cytokines or enzymes (e.g., collagenase). Both play an important role in inflammatory and immune reactions. According to the information provided, this negative expression appears to play a key function in anti-inflammatory and immunosuppressive effects of the glucocorticoids. Anti-inflammatory activity of representative glucocorticoids is presented below (**Table 1**). Dexamethasone and betamethasone are two glucocorticoids with the highest anti-inflammatory activity. If cortisol has antiinflammatory activity defined as 1, then prednisone, prednisolone, triamcinolone, and 6α-methylprednisolone have 4–5 times stronger anti-inflammatory properties, with longer half-life than cortisol. Examples of representative glucocorticoids and their properties are shown in **Table 1**.

**159**

affect:

**Table 1.**

further reactions.

retention of Na<sup>+</sup>

may occur.

*Role of Glucocorticoids in Hearing Preservation in Partial Deafness Treatment*

Cortisol 1 Short: t1/2 = 8–12 Cortisone 0.8 Short: t1/2 = 8–12

Fludrocortisone 10 Intermediate: t1/2 = 12–36 Prednisone 4 Intermediate: t1/2 = 12–36 Prednisolone 4 Intermediate: t1/2 = 12–36 6α-methylprednisone 5 Intermediate: t1/2 = 12–36 Triamcinolone 5 Intermediate: t1/2 = 12–36 Betamethasone 25 Long: t1/2 = 36–72 Dexamethasone 25 Long: t1/2 = 36–72

**Anti-inflammatory activity Biological half-life t1/2 (h)**

*DOI: http://dx.doi.org/10.5772/intechopen.88863*

**1.2 Functions and activity of glucocorticoids**

*Characteristics of representative corticosteroids [5].*

of fat tissue known as Cushing's syndrome.

may affect the cardiovascular system.

The two key roles glucocorticoids play as biological and pharmaceutical compounds are anti-inflammatory and immunosuppressive roles. Glucocorticoids also

1.Carbohydrate and protein metabolism. Glucocorticoids stimulate the liver to form glucose in biochemical reaction (gluconeogenesis) from amino acids and glycerol or/and stimulate the liver to release glucose from glycogen. At the same time, the diminishing of glucose is reduced, reaction of lipolysis and protein breakdown increases, and as a result the blood glucose level rises. Patients suffering from diabetes or other forms of hyperglycemia during glucocorticoid therapy should be under special control. Glucocorticoids induce increased protein metabolism and deliver compounds such as amino acids for

2.Lipid metabolism. One effect of therapy with corticosteroids is redistribution

3.Water and electrolyte balance. Glucocorticoids exert negatively on metabolism of Ca2+ due to reduction of absorption from the digestive system and increased excretion via kidneys. Prophylaxis of osteoporosis requires supplementation of Ca2+ ions and physical activity adequate to possibilities of patient. Additionally, glucocorticoids reduce activity of osteoclasts and stimulate the activity of osteoblasts. Glucocorticoid therapy sometimes may cause increased

ions and decrease in concentration of K<sup>+</sup>

interaction with receptor for mineralocorticoids. The deterioration in ion level

4.Impaired wound healing. Due to reduction of synthesis of collagen, glycosaminoglycans and disturbance in fibroblast function problem with healing wound

5.Anti-inflammatory and immunosuppressive activity. Glucocorticoids can suppress or prevent inflammatory reactions in different ways: reduction in diapedesis of granulocytes and proliferation of lymphocytes Th, inhibition/

ions because of

*Role of Glucocorticoids in Hearing Preservation in Partial Deafness Treatment DOI: http://dx.doi.org/10.5772/intechopen.88863*


## **Table 1.**

*The Human Auditory System - Basic Features and Updates on Audiological Diagnosis and Therapy*

the nonsurgical factors that could contribute to improve rates of hearing preservation in preoperative, during surgery, or in postoperative period in patients who suffer from partial deafness. One of the approaches of many leading research centers is using pharmacotherapy (glucocorticoids) as a factor which may improve hearing functions following cochlear implantation [1, 2]. Glucocorticoids play an important role in pharmacotherapy of many different otorhinolaryngological diseases, such as Meniere's disease, sudden sensorineural hearing loss (SSNHL), and tinnitus, and as a part of otorhinolaryngological procedures in surgeries (e.g., cochlear implantation) [3, 4]. The effects of treatment listed diseases are different and mainly depend on treatment results, adverse effects of used medications, and additional pharmacological treatment that was used during treatment. Unfortunately, the side effects of glucocorticoids are serious, and as the result, sometimes pharmacotherapy has to

On the one hand, insertion of specific electrode of cochlear implant requires perfection in surgical techniques, but on the other it is difficult to do perfectly. Clinically approved algorithm of corticosteroid therapy (local or systematic) is discussed as one factor in reducing oxidative stress, an inflammatory reaction, and as a result apoptosis of hearing cells. A major challenge in effective administration and delivery medicines is the *blood-labyrinth barrier* (BLB) and physical inaccessibility of the inner ear, especially the apical part of the cochlea. It seems to be crucial especially for patients who suffer from partial deafness (PD) (apical hair cells are

The adrenal cortex synthesizes two classes of steroids: corticosteroids (mineralocorticoids and glucocorticoids) and androgens. One of the differences is the number of carbon atoms. Corticosteroids have 21 carbon atoms, and androgens have 19 carbon atoms. In the human body, the main glucocorticoid is cortisol, and

Glucocorticoid receptor (GR) is located in the cytoplasm in inactive form until it binds with the molecule of glucocorticoid. This action results in activation of receptor and translocation complex: *glucocorticoid receptor for glucocorticoid* to the nucleus. Activation of receptor is based on dissociation from the associated proteins. After translocation to the nucleus, a complex of glucocorticoid receptor interacts with specific, short DNA sequences with the regulatory regions. The regions are termed *glucocorticoid responsive elements* (GREs) and allow induction of the gene transcription by glucocorticoids. This process is very complicated because of interaction with specific cofactors and proteins and still not well and completely understood by scientists and researchers [5]. Not only positive response to glucocorticoid is possible. According to Webster and Cidlowski, genes negatively regulated by glucocorticoids were also identified [6]. An example of downregulation (negative regulation) is to repress the expression of gene responsible for encoding cytokines or enzymes (e.g., collagenase). Both play an important role in inflammatory and immune reactions. According to the information provided, this negative expression appears to play a key function in anti-inflammatory and immunosuppressive effects of the glucocorticoids. Anti-inflammatory activity of representative glucocorticoids is presented below (**Table 1**). Dexamethasone and betamethasone are two glucocorticoids with the highest anti-inflammatory activity. If cortisol has antiinflammatory activity defined as 1, then prednisone, prednisolone, triamcinolone, and 6α-methylprednisolone have 4–5 times stronger anti-inflammatory properties, with longer half-life than cortisol. Examples of representative glucocorticoids and

be stopped, and discontinuation of therapy is the only solution.

responsible for receiving low frequencies).

the main mineralocorticoid is aldosterone [5].

their properties are shown in **Table 1**.

**1.1 Characteristic: glucocorticoids**

**158**

*Characteristics of representative corticosteroids [5].*
