RESUMO
Hypoxia is the major cause of acute altitude hypoxia injury in acute mountain sickness (AMS). YQ23 is a kind of novel bovine-derived, cross-linked hemoglobin-based oxygen carrier (HBOC). It has an excellent capacity for carrying and releasing oxygen. Whether YQ23 has a protective effect on the acute altitude hypoxia injury in AMS is unclear. In investigating this mechanism, the hypobaric chamber rabbit model and plain-to-plateau goat model were used. Furthermore, this study measured the effects of YQ23 on the ability of general behavior, general vital signs, Electrocardiograph (ECG), hemodynamics, vital organ injury markers, and blood gases in hypobaric chamber rabbits and plain-to-plateau goats. Our results showed that the ability of general behavior (general behavioral scores, GBS) (GBS: 18 ± 0.0 vs. 14 ± 0.5, p < 0.01) and the general vital signs weakened [Heart rate (HR, beats/min): 253.5 ± 8.7 vs. 301.1 ± 19.8, p < 0.01; Respiratory rate (RR, breaths/min): 86.1 ± 5.2 vs. 101.2 ± 7.2, p < 0.01] after exposure to plateau environment. YQ23 treatment significantly improved the ability of general behavior (GBS: 15.8 ± 0.5 vs. 14.0 ± 0.5, p < 0.01) and general vital signs [HR (beats/min): 237.8 ± 24.6 vs. 301.1 ± 19.8, p < 0.01; RR (breaths/min): 86.9 ± 6.6 vs. 101.2 ± 7.2, p < 0.01]. The level of blood PaO2 (mmHg) (115.3 ± 4.7 vs. 64.2 ± 5.6, p < 0.01) and SaO2(%) (97.7 ± 0.7 vs. 65.8 ± 3.1, p < 0.01) sharply decreased after exposure to plateau, YQ23 treatment significantly improved the blood PaO2 (mmHg) (97.6 ± 3.7 vs. 64.2 ± 5.6, p < 0.01) and SaO2(%) (82.7 ± 5.2 vs. 65.8 ± 3.1, p < 0.01). The cardiac ischemia and injury marker was increased [troponin (TnT, µg/L):0.08 ± 0.01 vs. 0.12 ± 0.02, p < 0.01], as well as the renal [blood urea nitrogen (BUN, mmol/L): 6.0 ± 0.7 vs. 7.3 ± 0.5, p < 0.01] and liver injury marker [alanine aminotransferase (ALT, U/L): 45.8 ± 3.6 vs. 54.6 ± 4.2, p < 0.01] was increased after exposure to a plateau environment. YQ23 treatment markedly alleviated cardiac ischemia [TnT (µg/L):0.10 ± 0.01 vs 0.12 ± 0.02, p < 0.01] and mitigated the vital organ injury. Besides, YQ23 exhibited no adverse effects on hemodynamics, myocardial ischemia, and renal injury. In conclusion, YQ23 effectively alleviates acute altitude hypoxia injury of AMS without aside effects.
RESUMO
PURPOSE: Adjunct chemoradiation is offered to unresectable esophageal squamous cell carcinoma (ESCC) patients, while its use is limited in tumors with strong resistance. Oxygen carriers or anti-hypoxic drugs belong to an emerging class of regulators that can alleviate tumor hypoxia. METHODS: We investigate the potential use of a novel oxygen carrier YQ23 in sensitizing chemoresistant ESCC in a series of subcutaneous tumor xenograft models developed using ESCC cell lines with different strengths of chemosensitivities. RESULTS: Tumor xenografts were developed using SLMT-1 and HKESC-2 ESCC cell lines with different strengths of resistance to two chemotherapeutic drugs, 5-fluorouracil and cisplatin. More resistant SLMT-1 xenografts responded better to YQ23 treatment than HKESC-2, as reflected by the induced tumor oxygen level. YQ23 sensitized SLMT-1 xenografts toward 5-fluorouracil via its effect on reducing the level of a hypoxic marker HIF-1α. Furthermore, a derangement of tumor microvessel density and integrity was demonstrated with a concurrent decrease in the level of a tumor mesenchymal marker vimentin. Similar to the 5-fluorouracil sensitizing effect, YQ23 also enhanced the response of SLMT-1 xenografts toward cisplatin by reducing the tumor size and the number of animals with invasive tumors. Chemosensitive HKESC-2 xenografts were irresponsive to combined YQ23 and cisplatin treatment. CONCLUSIONS: In all, YQ23 functions selectively on chemoresistant ESCC xenografts, which implicates its potential use as a chemosensitizing agent for ESCC patients.