Effect of Thiamine Pyrophosphate on Oxidative Damage to the Oropharyngeal, Nasal and Cochlear Tissues Induced by Doxorubicin in Guinea Pigs

Abstract

Doxorubicin (DOX) inhibits the enzyme tyaminpyrophosphokinase (TPK). Hence the synthesis of thiamine pyrophosphate (TPP) which is the active metabolite of thiamine stops. This leads to oxidative damage. In the literature, no studies on the protective effect of TPP against doxorubicin-induced oropharyngeal, nose and cochlear oxidative damage were found. In this study was investigated whether DOX produces oxidative stress in the oropharyngeal, nose and cochlea of animals and it examines the protective effect of TPP against DOX toxicity on these tissues. Guinea pig experimental animals were divided into groups as the controls. One group was given DOX, another group was given TPP + doxorubicin (TDOX) and the final group was the healthy group (HG). The TDOX group (n = 6) received an intraperi-toneal (ip) injection of 25 mg/kg TPP. The DOX (n = 6) and HG (n = 6) animals were given distilled water in the same way. TDOX and DOX animals were administered ip 5 mg/kg DOX one hour after the administration of TPP and distilled water once a day for seven days. At the end of this period, animals were sacri-fied with a high dose of anesthesia and the levels of malondialdehyde (MDA), myeloperoxidase (MPO), ni-tric oxide (NO), total glutathione (tGSH) and glutathione reductase (GSHRd) were determined in the removed oropharyngeal, nasal, and cochlear tissues. In addition, the TNF-α gene expression was measured. DOX was demonstrated to significantly increase the levels of MDA, MPO and NO and to reduce the levels of tGSH and GSHRd in the oropharyngeal, nasal and cochlear tissues of animals. TPP prevented the increase of the levels of MDA, MPO, NO and TNF-α with doxorubicin. TPP supressed the oxidative stress induced by DOXin the oropharyngeal, nasal and cochlear tissues. It can be suggested that TPP can be used against DOX toxicity © 2017, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.