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Salivary Redox Biomarkers in Insulin Resistance: Preclinical Studies in an Animal Model
Oxidative Medicine and Cellular Longevity Pub Date : 2021-09-14 , DOI: 10.1155/2021/3734252
Mateusz Maciejczyk 1 , Cezary Pawlukianiec 2 , Małgorzata Żendzian-Piotrowska 1 , Jerzy Robert Ładny 3 , Anna Zalewska 4
Affiliation  

Insulin resistance (IR) is a condition of impaired tissue response to insulin. Although there are many methods to diagnose IR, new biomarkers are still being sought for early and noninvasive diagnosis of the disease. Of particular interest in laboratory diagnostics is saliva collected in a stress-free, noninvasive, and straightforward manner. The purpose of the study was to evaluate the diagnostic utility of salivary redox biomarkers in preclinical studies in an animal model. The study was conducted on 20 male Wistar rats divided into two equal groups: a standard diet and a high-fat diet (HFD). In all rats fed the HFD, IR was confirmed by an elevated homeostasis model assessment (HOMA-IR) index. We have shown that IR is responsible for the depletion of the enzymatic (↓superoxide dismutase) and nonenzymatic (↓ascorbic acid, ↓reduced glutathione (GSH)) antioxidant barrier at both the central (serum/plasma) and salivary gland (saliva) levels. In IR rats, we also demonstrated significantly higher concentrations of protein/lipid oxidation (↑protein carbonyls, ↑4-hydroxynoneal (4-HNE)), glycation (↑advanced glycation end products), and nitration (↑3-nitrotyrosine) products in both saliva and blood plasma. Salivary nonenzymatic antioxidants and oxidative stress products generally correlate with their blood levels, while GSH and 4-HNE have the highest correlation coefficient. Salivary GSH and 4-HNE correlate with body weight and BMI and indices of carbohydrate metabolism (glucose, insulin, HOMA-IR) and proinflammatory adipokines (leptin, resistin, TNF-α). These biomarkers differentiate IR from healthy controls with very high sensitivity (100%) and specificity (100%). The high diagnostic utility of salivary GSH and 4-HNE is also confirmed by multivariate regression analysis. Summarizing, saliva can be used to assess the systemic antioxidant status and the intensity of systemic oxidative stress. Salivary GSH and 4-HNE may be potential biomarkers of IR progression. There is a need for human clinical trials to evaluate the diagnostic utility of salivary redox biomarkers in IR conditions.

中文翻译:

胰岛素抵抗中的唾液氧化还原生物标志物:动物模型的临床前研究

胰岛素抵抗 (IR) 是组织对胰岛素的反应受损的一种情况。尽管有许多诊断 IR 的方法,但仍在寻找新的生物标志物用于疾病的早期和非侵入性诊断。实验室诊断中特别感兴趣的是以无压力、无创和直接的方式收集唾液。该研究的目的是评估唾液氧化还原生物标志物在动物模型临床前研究中的诊断效用。该研究对 20 只雄性 Wistar 大鼠进行,分为两组:标准饮食和高脂饮食 (HFD)。在所有喂食 HFD 的大鼠中,IR 通过升高的稳态模型评估 (HOMA-IR) 指数得到证实。我们已经表明,IR 是导致酶(↓超氧化物歧化酶)和非酶(↓抗坏血酸,↓降低谷胱甘肽 (GSH)) 在中央(血清/血浆)和唾液腺(唾液)水平的抗氧化屏障。在 IR 大鼠中,我们还展示了显着更高浓度的蛋白质/脂质氧化(↑蛋白质羰基化合物、↑4-羟基壬醛(4-HNE))、糖基化(↑高级糖基化终产物)和硝化(↑3-硝基酪氨酸)产物。唾液和血浆。唾液非酶抗氧化剂和氧化应激产物通常与其血液水平相关,而 GSH 和 4-HNE 的相关系数最高。唾液 GSH 和 4-HNE 与体重和 BMI 以及碳水化合物代谢(葡萄糖、胰岛素、HOMA-IR)和促炎性脂肪因子(瘦素、抵抗素、TNF- 我们还证明唾液和血液中的蛋白质/脂质氧化(↑蛋白质羰基化合物、↑4-羟基壬醛(4-HNE))、糖基化(↑高级糖基化终产物)和硝化(↑3-硝基酪氨酸)产物浓度显着升高等离子体。唾液非酶抗氧化剂和氧化应激产物通常与其血液水平相关,而 GSH 和 4-HNE 的相关系数最高。唾液 GSH 和 4-HNE 与体重和 BMI 以及碳水化合物代谢(葡萄糖、胰岛素、HOMA-IR)和促炎性脂肪因子(瘦素、抵抗素、TNF- 我们还证明唾液和血液中的蛋白质/脂质氧化(↑蛋白质羰基化合物、↑4-羟基壬醛(4-HNE))、糖基化(↑高级糖基化终产物)和硝化(↑3-硝基酪氨酸)产物浓度显着升高等离子体。唾液非酶抗氧化剂和氧化应激产物通常与其血液水平相关,而 GSH 和 4-HNE 的相关系数最高。唾液 GSH 和 4-HNE 与体重和 BMI 以及碳水化合物代谢(葡萄糖、胰岛素、HOMA-IR)和促炎性脂肪因子(瘦素、抵抗素、TNF- 唾液非酶抗氧化剂和氧化应激产物通常与其血液水平相关,而 GSH 和 4-HNE 的相关系数最高。唾液 GSH 和 4-HNE 与体重和 BMI 以及碳水化合物代谢(葡萄糖、胰岛素、HOMA-IR)和促炎性脂肪因子(瘦素、抵抗素、TNF- 唾液非酶抗氧化剂和氧化应激产物通常与其血液水平相关,而 GSH 和 4-HNE 的相关系数最高。唾液 GSH 和 4-HNE 与体重和 BMI 以及碳水化合物代谢(葡萄糖、胰岛素、HOMA-IR)和促炎性脂肪因子(瘦素、抵抗素、TNF-α )。这些生物标志物以非常高的敏感性 (100%) 和特异性 (100%) 将 IR 与健康对照区分开来。多变量回归分析也证实了唾液 GSH 和 4-HNE 的高诊断效用。总之,唾液可用于评估全身抗氧化状态和全身氧化应激的强度。唾液 GSH 和 4-HNE 可能是 IR 进展的潜在生物标志物。需要进行人体临床试验来评估唾液氧化还原生物标志物在 IR 条件下的诊断效用。
更新日期:2021-09-14
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