## 5 Discussion
These unique results support the idea that the tissue repair and inflammatory resolution may be therapeutically enhanced by combining glucocorticoidoid and AAT therapies at ideal dose ratios or as interleaving treatment protocols to achieve optimized outcomes in which inflammatory branches are executed for the sake of decontamination and tissue repair whilst the desired immunosuppressive effects of glucocorticoids persist. It is also reasonable to propose that such a combination may allow for a reduction in glucocorticoid doses, thereby minimizing the adverse effects of a glucocorticoidoid therapy. The role of AAT in the taming of excess free radicals brings to mind antioxidant approaches for the conditions of tissue damage. Many destructive inflammatory processes are mediated by free radicals, including trauma-related processes in the inner ear and exposure to ototoxic drugs that subsequently lead to hair cell death. With this notion in mind, a trial conducted in Hannover Medical School, Germany, tested the effect of a treatment with an antioxidant dietary supplement combination (including vitamins A, C, E and magnesium) on the preservation of residual hearing [84]. The treatment was provided to patients for a duration of 106 days, starting 2 days prior to surgery. Although a statistical significance was not observed, the results showed a positive trend as the treated patients exhibited a 4.15 dB lower threshold than the placebo group at 500 Hz three months after the first fitting. One year after surgery, this disparity increased to 6.45 dB between the groups. It is suggested that a possible mechanism of action of AAT regarding hair cell protection could be in modulating excessive oxidative stress. This action may benefit inner ear disorders, including as an adjunct therapeutic alongside glucocorticoids. Cochlear implants, stages surgery and idiopathic perilymph fistulas are all examples of _sterile inner ear injuries_. As such, a local inflammation arises independent of pathogens as the cell injury and mechanical stress that occur within the cochlear microstructure readily spread the inflammation. This is not unlike a sterile inflammation in, for example, cardiac ischemias and cerebral strokes as well as kidney ischemia-reperfusion injuries; the injured cells are extremely inflammatory. In these circumstances, AAT has been shown to be of benefit at multiple levels, including in regard to neutrophific infiltration, TNF\(\alpha\) production and systemic CRP levels [15, 85, 86, 87]. AAT has been tested for middle ear treatments in animals and did not exhibit ototoxicity [88, 89]; in humans, the effect of AAT was tested on middle ear effusions and was found to interfere with destructive enzymes [90]. Considering the pattern of the intimate protection of injured tissues by AAT, in the context of inner ear disorders, it would be tempting to explore the possibility of applying AAT in the electrode-eluting arrays that presently infuse dexamethasone directly into the cochlear compartment or for improving the outcomes of the novel technology of vestibular implants [91]. In conclusion, the steroid inhibition of the early inflammatory surge is, in many ways, detrimental because it prevents the unfolding of the repair processes that are essential for the actual resolution of wounded tissues. There is strong experimental and clinical support for the capacity of an AAT therapy to advance the tissue healing processes in a safe and physiologically appropriate setting either alone or possibly in a calculated conjunction with glucocorticoids. The idea of treating a tissue repair rather than treating an inflammation opens opportunities for many more unmet clinical indications outside the scope of the current review. Further research is required to better understand the delicate synergy between glucocorticoids and AAT and to identify optimal timings and dosages across the various pathologies. Conceptualization, A.A., S.E.-S. and E.C.L. ; methodology, A.A., S.E.-S. and E.C.L. ; investigation, A.A., S.E.-S. and E.C.L.