纠正紫杉醇诱发神经病变动物唾液腺的病理变化。

K Tykhonovych, T Kryvoruchko, N Nikitina, S Berehovyi, K Neporada
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引用次数: 0

摘要

背景:紫杉醇是一种用于治疗乳腺癌、卵巢癌和其他癌症的高效化疗药物。目的:本研究旨在探讨紫杉醇诱导的周围神经病变对动物唾液腺病理变化发展的影响,并探讨用维生素 B/ATP 复合物纠正已发现变化的可能性:为了模拟中毒性神经病变,动物体内/体外注射紫杉醇2毫克/千克,连续4天。为了纠正已发现的变化,给大鼠注射维生素 B/ATP 复合物(1 毫克/千克),连续 9 天。测定了颌下腺匀浆中的α-淀粉酶活性、总蛋白水解活性、总抗胰蛋白酶活性、中等质量分子含量、硫代巴比妥酸活性物质(TBARS)、氧化修饰蛋白质和过氧化氢酶活性:结果:与完整动物的这些参数相比,中毒性神经病变动物唾液腺中氧化修饰的蛋白质、中质分子和 TBARS 的含量明显增加,过氧化氢酶和淀粉酶的活性明显下降。在紫杉醇诱导的神经病变背景下,连续 9 天服用维生素 B/ATP 复合物可使抗胰蛋白酶活性和淀粉酶活性恢复正常,氧化修饰的蛋白质、中等质量分子和 TBARS 的含量显著降低,与未治疗的神经病变大鼠相比,动物唾液腺中过氧化氢酶的活性显著提高:结论:紫杉醇诱导的神经病变导致大鼠唾液腺发生病理变化,表现为羰基氧化应激和蛋白质合成功能受损。维生素 B/ATP 复合物可恢复大鼠唾液腺的蛋白质合成功能和蛋白酶抑制剂平衡,抑制氧化应激,使自由基过程恢复正常。
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CORRECTION OF PATHOLOGICAL CHANGES IN SALIVARY GLANDS OF ANIMALS WITH PACLITAXEL-INDUCED NEUROPATHY.

Background: Paclitaxel is a highly effective chemotherapeutic agent used to treat breast, ovarian, and other cancers. At the same time, paclitaxel causes peripheral neuropathy as a side effect in 45%-70% of patients.

Aim: The aim of the study was to investigate the effect of paclitaxel-induced peripheral neuropathy on the development of pathological changes in the salivary glands of animals and to explore the possibility of correction of the identified changes with vitamin B/ATP complex.

Materials and methods: To simulate toxic neuropathy, animals were injected i/p with paclitaxel 2 mg/kg for 4 days. In order to correct the identified changes, rats were injected i/m with vitamin B/ATP complex (1 mg/ kg) for 9 days. In the homogenate of the submandibular salivary glands, α-amylase activity, total proteolytic activity, total antitryptic activity, the content of medium mass molecules, thiobarbituric acid reactive substances (TBARS), oxidatively modified proteins, and catalase activity were determined.

Results: A significant increase in the content of oxidatively modified proteins, medium mass molecules, and the content of TBARS and significant decrease in the activity of catalase and amylase were determined in the salivary glands of animals with toxic neuropathy compared to these parameters in intact animals. Administration of vitamin B/ATP complex for 9 days against the background of paclitaxel-induced neuropathy led to normalization of antitryptic activity and amylase activity, a significant decrease in the content of oxidatively modified proteins, medium mass molecules, and TBARS along with a significant increase in catalase activity in the salivary glands of animals compared to the untreated rats with neuropathy.

Conclusion: Paclitaxel-induced neuropathy caused the development of pathological changes in the salivary glands of rats, which was evidenced by a carbonyl- oxidative stress and impaired protein synthetic function. The correction with vitamin B/ATP complex restored the protein-synthetic function and the proteinase-inhibitor balance, suppressed the oxidative stress and normalized free radical processes in the salivary glands of rats.

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