The Role of Thiamine Pyrophosphate in Prevention of Cisplatin Ototoxicity in an Animal Model

Abstract

Objective. The aim of this study was to evaluate the effectiveness of thiamine pyrophosphate against cisplatin-induced ototoxicity in guinea pigs. Materials and Methods. Healthy guinea pigs (n = 18) were randomly divided into three groups. Group 1 (n = 6) received an intraperitoneal injection of saline solution and cisplatin for 7 days, group 2 (n = 6) received an intraperitoneal injection of thiamine pyrophosphate and cisplatin for 7 days, and group 3 (n = 6) received only intraperitoneal injection of saline for 7 days. The animals in all groups were sacrificed under anesthesia, and their cochleas were harvested for morphological and biochemical observations. Results. In group 1, receiving only cisplatin, cochlear glutathione concentrations, superoxide dismutase, and glutathione peroxidase activities significantly decreased (P < 0.05) and malondialdehyde concentrations significantly increased (P < 0.05) compared to the control group. In group 2, receiving thiamine pyrophosphate and cisplatin, the concentrations of enzymes were near those of the control group. Microscopic examination showed that outer hair cells, spiral ganglion cells, and stria vascularis were preserved in group 2. Conclusion. Systemic administration of thiamine pyrophosphate yielded statistically significant protection to the cochlea of guinea pigs from cisplatin toxicity. Further experimental animal studies are essential to determine the appropriate indications of thiamine pyrophosphate before clinical use.

Thiamine increases the resistance of baker's yeastSaccharomyces cerevisiaeagainst oxidative, osmotic and thermal stress, through mechanisms partly independent of thiamine diphosphate-bound enzymes

“…On the other hand, SOD1 gene has been shown to interact with thiamine biosynthetic regulatory gene THI2 (Zheng et al ., ), showing that the network between thiamine, TDP and defence systems are probably much more complicated than previously presumed. An interesting example of those interactions has been also provided by two different groups, who reported that an oral administration of TDP but not thiamine yielded significant protection against cisplatin and metotrexate toxicity, making the above‐mentioned dependencies even more sophisticated (Demiryilmaz et al ., ; Kuduban et al ., ).…”

“…than previously presumed. An interesting example of those interactions has been also provided by two different groups, who reported that an oral administration of TDP but not thiamine yielded significant protection against cisplatin and metotrexate toxicity, making the abovementioned dependencies even more sophisticated (Demiryilmaz et al, 2012;Kuduban et al, 2013).…”

Effect of rutin on oxidative and proinflammatory damage induced by cisplatin in blood serum, ureter, bladder and urethra in rats

“…In recent studies, cisplatin-induced neuropathic pain has been associated with oxidative stress [5]. It has also been documented that cisplatin causes damage to the inner ear tissue with oxidative stress [6]. It has been reported that the oxidative damage caused by cisplatin in the cardiovascular tissue is reduced by an antioxidant drug [7].…”

Survival of auditory hair cells

“…Evidence from mammalian models lacking hair cell regenerative capacity is equally compelling, both in the context of drug-induced ototoxicity and noise-induced hearing loss. Systemic administration of thiamine pyrophosphate, the active form of the metabolism and antioxidation cofactor thiamine, preserved cochlear antioxidant levels and activities, as well as the presence of hair cells in cisplatin-treated guinea pigs, though hair cell quantification was not part of the analysis (Kuduban et al, 2013). Antioxidant extracts from Ginkgo biloba leaves displayed a dose-dependent attenuation of cisplatin-induced hair cell death and threshold elevations in rat models (Choi et al, 2013).…”