阐明 L-精氨酸和 N-硝基-L-精氨酸在不同缺氧耐受水平的大鼠和接触硝酸铅治疗中的作用。

Elucidation of the Role of L-Arginine and N-Nitro-L-Arginine in the Treatment of Rats with Different Levels of Hypoxic Tolerance and Exposure to Lead Nitrate.

机构信息

Institute of Biology, Pomeranian University in Słupsk, Arciszewski Str. 22b, 76-200 Słupsk, Poland.

Department of Ecology, Geography and Nature Management, T.H. Shevchenko National University "Chernihiv Colehium", 53 Hetmana Polubotka Str., Chernihiv, 14013, Ukraine.

出版信息

Cell Physiol Biochem. 2024 Jul 30;58:336-360. doi: 10.33594/000000716.

DOI:10.33594/000000716

PMID:39092511

Abstract

BACKGROUND/AIMS: Individual resistance to hypoxia is an important feature of the physiological profile of an organism, particularly in relation to lead-induced toxicity.

METHODS

Our study focused on evaluating parameters of mitochondrial oxygen consumption, microsomal oxidation, intensity of lipoperoxidation processes and antioxidant defences in the liver of rats with low (LR) and high (HR) resistance to hypoxia to elucidate the mechanisms of action of L-arginine and the NO synthase inhibitor L-NNA before or after exposure to lead nitrate.

RESULTS

Our study suggests that the redistribution of oxygen-dependent processes towards mitochondrial processes under the influence of the nitric oxide precursor amino acid L-arginine is an important mechanism for maintaining mitochondrial respiratory chain function during lead nitrate exposure (3.6 mg lead nitrate/kg bw per day for 30 days). Animals were given L-arginine at a dose of 600 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate or the NO synthase inhibitor N-nitro-L-arginine (L-NNA) at a dose of 35 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate. Our experiments demonstrated the efficacy of using lead nitrate to simulate lead-related toxic processes via Pb levels in liver tissue; we demonstrated significantly reduced levels of nitrites and nitrates, i.e. stable metabolites of the nitric oxide system, in both LR and HR animals. The effect of the amino acid L-arginine stabilised the negative effects of lead nitrate exposure in both groups of LR and HR rats. We observed the efficiency of mitochondrial energy supply processes and showed a greater vulnerability of NADH-dependent oxidation during lead nitrate exposure in the liver of HR rats.

CONCLUSION

L-arginine initiated the processes of oxidation of NADH-dependent substrates in the LR group, whereas in the HR group this directionality of processes was more effective when the role of the nitric oxide system was reduced (use of L-NNA). Our study of key antioxidant enzyme activities in rat liver tissue during lead nitrate exposure revealed changes in the catalase-peroxidase activity ratio. We found different activities of antioxidant enzymes in the liver tissue of rats treated with lead nitrate and L-arginine or L-NNA, with a significant increase in GPx activity in the LR group when L-arginine was administered both before and after exposure to lead nitrate.

摘要

背景/目的：个体对缺氧的抵抗力是机体生理特征的一个重要特征，尤其是与铅诱导的毒性有关。

方法

我们的研究集中在评估低（LR）和高（HR）耐缺氧大鼠肝脏中线粒体氧消耗、微粒体氧化、脂质过氧化过程强度和抗氧化防御的参数，以阐明 L-精氨酸和一氧化氮合酶抑制剂 L-NNA 在暴露于硝酸铅之前或之后的作用机制。

结果

我们的研究表明，在硝酸铅暴露期间（每天 3.6 毫克硝酸铅/千克体重，持续 30 天），作为一氧化氮前体氨基酸 L-精氨酸的影响下，氧依赖过程向线粒体过程的重新分配是维持线粒体呼吸链功能的重要机制。在暴露于硝酸铅之前和之后，给动物注射 600mg/kg bw 的 L-精氨酸（腹腔内，30 分钟），或者在暴露于硝酸铅之前和之后，给动物注射 35mg/kg bw 的一氧化氮合酶抑制剂 N-硝基-L-精氨酸（L-NNA）（腹腔内，30 分钟）。我们的实验证明了使用硝酸铅模拟与铅相关的毒性过程的有效性，通过肝组织中的铅水平；我们在 LR 和 HR 动物中都观察到亚硝酸盐和硝酸盐水平显著降低，即一氧化氮系统的稳定代谢物。氨基酸 L-精氨酸稳定了 LR 和 HR 两组大鼠暴露于硝酸铅的负面影响。我们观察到了线粒体能量供应过程的效率，并显示了 HR 大鼠肝组织中硝酸铅暴露时 NADH 依赖性氧化的更大脆弱性。

结论

L-精氨酸在 LR 组中启动了 NADH 依赖性底物的氧化过程，而在 HR 组中，当一氧化氮系统的作用降低时（使用 L-NNA），这个过程的方向性更有效。我们在硝酸铅暴露期间研究了大鼠肝组织中关键抗氧化酶活性，发现了过氧化氢酶-过氧化物酶活性比的变化。我们发现了用硝酸铅和 L-精氨酸或 L-NNA 处理的大鼠肝组织中抗氧化酶活性的不同，当在暴露于硝酸铅之前和之后都给予 L-精氨酸时，LR 组的 GPx 活性显著增加。