Department of Medical Elementology and Toxicology, Faculty of Science, Hamdard University, New Delhi 110062, India.
Voiland School of Chemical Engineering and Bioengineering, Pullman, WA 99164, USA.
Molecules. 2022 Jul 7;27(14):4362. doi: 10.3390/molecules27144362.
Oxidative stress induced by well-known toxins including ferric nitrilotriacetate (Fe-NTA), carbon tetrachloride (CCl) and thioacetamide (TAA) has been attributed to causing tissue injury in the liver and kidney. In this study, the effect of glyceryl trinitrate (GTN), a donor of nitric oxide and NG-nitroarginine methyl ester (l-NAME), a nitric oxide inhibitor on TAA-induced hepatic oxidative stress, GSH and GSH-dependent enzymes, serum transaminases and tumor promotion markers such as ornithine decarboxylase (ODC) activity and [H]-thymidine incorporation in rats were examined. The animals were divided into seven groups consisting of six healthy rats per group. The six rats were injected intraperitoneally with TAA to evaluate its toxic effect, improvement in its toxic effect if any, or worsening in its toxic effect if any, when given in combination with GTN or l-NAME. The single necrogenic dose of TAA administration caused a significant change in the levels of both hepatic and serum enzymes such as glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), γ-glutamyl transpeptidase (GGT), glucose 6-phosphate dehydrogenase (G6PD), alanine aminotransferase (AST) and aspartate aminotransferase (ALT). In addition, treatment with TAA also augmented malondialdehyde (MDA), ornithine decarboxylase (ODC) activity and [H]-thymidine incorporation in rats liver. Concomitantly, TAA treatment depleted the levels of GSH. However, most of these changes were alleviated by the treatment of animals with GTN dose-dependently. The protective effect of GTN against TAA was also confirmed histopathologically. The present data confirmed our earlier findings with other oxidants including Fe-NTA and CCl. The GTN showed no change whatsoever when administered alone, however when it was given along with TAA then it showed protection thereby contributing towards defending the role against oxidants-induced organ toxicity. Overall, GTN may contribute to protection against TAA-induced oxidative stress, toxicity, and proliferative response in the liver, according to our findings.
已知包括铁氮川三乙酸盐（Fe-NTA）、四氯化碳（CCl）和硫代乙酰胺（TAA）在内的氧化应激物会导致肝脏和肾脏组织损伤。在这项研究中，我们研究了甘油三硝酸酯（GTN）——一种一氧化氮供体，以及一氧化氮抑制剂 NG-硝基精氨酸甲酯（l-NAME）对 TAA 诱导的肝氧化应激、GSH 和 GSH 依赖性酶、血清转氨酶以及鸟氨酸脱羧酶（ODC）活性和 [H]-胸腺嘧啶掺入等肿瘤促进标志物的影响。动物被分为七组，每组 6 只健康大鼠。6 只大鼠经腹腔注射 TAA，以评估其毒性作用，如果与 GTN 或 l-NAME 联合使用，观察其毒性作用是否改善或恶化。单次给予致坏死剂量的 TAA 会导致肝脏和血清酶（如谷胱甘肽 S-转移酶（GST）、谷胱甘肽还原酶（GR）、谷胱甘肽过氧化物酶（GPx）、γ-谷氨酰转肽酶（GGT）、葡萄糖 6-磷酸脱氢酶（G6PD）、丙氨酸氨基转移酶（AST）和天冬氨酸氨基转移酶（ALT））的水平发生显著变化。此外，TAA 处理还会增加大鼠肝脏中的丙二醛（MDA）、鸟氨酸脱羧酶（ODC）活性和 [H]-胸腺嘧啶掺入。同时，TAA 处理还会降低 GSH 的水平。然而，这些变化中的大多数都可以通过 GTN 剂量依赖性地治疗动物来缓解。GTN 对 TAA 的保护作用也通过组织病理学得到了证实。这些数据证实了我们之前用其他氧化剂（包括 Fe-NTA 和 CCl）所做的发现。GTN 单独使用时没有变化，但与 TAA 一起使用时则显示出保护作用，从而有助于对抗氧化剂诱导的器官毒性。总的来说，根据我们的研究结果，GTN 可能有助于防止 TAA 诱导的肝氧化应激、毒性和增殖反应。
