This dissertation investigates the impact of paclitaxel-, streptozotocin-, and ethanol-induced neuropathy on the development of pathological changes in the major salivary glands of animals as well as explores the potential therapeutic benefits of cocarboxylase, nicotinamide, cobalamin, and ATP in the experimental correction of the condition. This study demonstrates that administration of paclitaxel, streptozotocin, and prolonged alcohol exposure in rats suppressed the amylolytic activity of the submandibular and sublingual salivary glands in 1.63 times (P<0.05), 1.92 times (P<0.05), and 1.7 times (P<0.05), respectively, compared to intact animals. This suggests a reduction in protein synthesis function and/or altered enzyme conformation due to oxidative stress under the impact of highly reactive free radicals, reactive oxygen species, which leads to oxidative protein modification.
The pro-oxidant and antioxidant system of the major salivary glands in animals with paclitaxel-induced neuropathy showed a decompensated imbalance, as indicated by a 2.26-fold increase in TBA- reactive substances (P<0.05) and a 1.35-fold rise in OMP (P<0.05), alongside a significant decrease in catalase activity. In conditions of diabetic neuropathy, the balance of pro- and antioxidant system in the major salivary glands of animals remains compensated, as indicated by the absence of statistically significant changes in OMP levels, alongside a notable increase in catalase activity. The most pronounced carbonyl-oxidative stress in the submandibular and sublingual salivary glands was observed in cases of alcoholic neuropathy, compared to streptozotocin- and paclitaxel-induced neuropathy. In the major salivary glands of animals subjected to prolonged alcohol exposure, there was a 1.4-fold increase in TBA- reactive substances (P<0.05) and a 3.5-fold rise in OMP levels (P<0.05) compared to the control group. The administration of streptozotocin and paclitaxel in animals led to compensatory changes in the proteinase-inhibitory potential of the major salivary glands, as evidenced by a 2.75-fold (P<0.05) and 1.71-fold (P<0.05) increase in
antitryptic activity, respectively, with no statistically significant changes in total proteolytic activity compared to intact animals. Streptozotocin-induced diabetic neuropathy results in alterations to the parenchymal components within the lobules of the submandibular salivary glands of rats. These changes manifest as dystrophic and destructive alterations in the
epithelial cells of the acinar and ductal structures, as well as impaired blood perfusion in the hemomicrocirculatory vessels. The combination of thiamine pyrophosphate, nicotinamide, cobalamin, and ATP prevents nerve conduction disorders induced by paclitaxel, streptozotocin, and ethanol, as evidenced by a significant reduction in pain sensitivity thresholds
by 28.75% (P<0.05), 109.2% (P<0.05), and 54.7% (P<0.05), respectively. The administration of this complex in streptozotocin- and paclitaxel-induced neuropathy mitigates oxidative stress that is demonstrated by a significant decrease in content of lipid peroxidation products: diene conjugates in 1.54 and 1.95 times (P<0.05), TBA- reactive substances in 1.8 and 2.23 times (P<0.05), and Schiff bases in 2 and 2.83 times (P<0.05) in the blood serum, alongside the normalization of antioxidant defense mechanisms. Metabolic correction of experimental paclitaxel-, streptozotocin-, and ethanol-induced neuropathy using neurotropic vitamins — thiamine, nicotinamide, cyanocobalamin, and ATP — administered over 9 days restored the protein-synthetic function of the major salivary glands in rats, suppressed oxidative stress, and normalized the proteinase-inhibitor balance. These findings underscore the practical significance of this study in preventing pathological changes in the salivary glands associated with complications from diabetes mellitus, chemotherapy for cancerous diseases, and alcoholism.
Key words: salivary glands, neuropathy, streptozocin, paclitaxel, ethanol, oxidative stress, reactive oxygen species, lipid peroxidation, toxicity, vitamins, thiamine, cyanocobalamin, chemotherapy, antioxidant defense, rats.
