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

IF 2.5 Q3 CELL BIOLOGY
Halina Tkaczenko, Oleksandr Lukash, Piotr Kamiński, Natalia Kurhaluk
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引用次数: 0

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 per os 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 Nω-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.

阐明L-精氨酸和Nω-硝基-L-精氨酸在治疗不同缺氧耐受性和暴露于硝酸铅的大鼠中的作用
背景/目的:个体对缺氧的抵抗力是生物体生理特征的一个重要特征,尤其是在铅诱导毒性方面:我们的研究重点是评估低耐受性(LR)和高耐受性(HR)大鼠肝脏中线粒体耗氧量、微粒体氧化、脂过氧化过程强度和抗氧化防御能力等参数,以阐明在接触硝酸铅之前或之后左旋精氨酸和 NO 合酶抑制剂 L-NNA 的作用机制:我们的研究表明,在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在暴露于硝酸铅(每天 3.6 毫克硝酸铅/千克体重,持续 30 天)期间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,给动物服用剂量为 600 毫克/千克体重(静注,30 分钟)的 L-精氨酸或剂量为 35 毫克/千克体重(静注,30 分钟)的 NO 合酶抑制剂 Nω-硝基-L-精氨酸(L-NNA)。我们的实验证明了使用硝酸铅通过肝脏组织中的铅含量来模拟铅相关毒性过程的有效性;我们还证明了亚硝酸盐和硝酸盐(即一氧化氮系统的稳定代谢产物)在 LR 和 HR 动物中的含量显著降低。氨基酸 L-精氨酸的作用稳定了硝酸铅暴露对 LR 和 HR 两组大鼠的负面影响。我们观察了线粒体能量供应过程的效率,发现在接触硝酸铅的过程中,HR 大鼠肝脏中依赖 NADH 的氧化作用更加脆弱:结论:在 LR 组中,L-精氨酸启动了 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(使用 L-NNA)时,这种过程的方向性更为有效。我们对接触硝酸铅期间大鼠肝脏组织中关键抗氧化酶活性的研究显示,过氧化氢酶-过氧化物酶活性比率发生了变化。我们发现,用硝酸铅和左旋精氨酸或左旋 NNA 处理的大鼠肝组织中抗氧化酶的活性不同,在暴露于硝酸铅之前和之后服用左旋精氨酸时,LR 组 GPx 活性显著增加。
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来源期刊
CiteScore
5.80
自引率
0.00%
发文量
86
审稿时长
1 months
期刊介绍: Cellular Physiology and Biochemistry is a multidisciplinary scientific forum dedicated to advancing the frontiers of basic cellular research. It addresses scientists from both the physiological and biochemical disciplines as well as related fields such as genetics, molecular biology, pathophysiology, pathobiochemistry and cellular toxicology & pharmacology. Original papers and reviews on the mechanisms of intracellular transmission, cellular metabolism, cell growth, differentiation and death, ion channels and carriers, and the maintenance, regulation and disturbances of cell volume are presented. Appearing monthly under peer review, Cellular Physiology and Biochemistry takes an active role in the concerted international effort to unravel the mechanisms of cellular function.
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