Nitric Oxide Synthase and Nitric Oxide Involvement in Different Toxicities

Abstract

Nitric oxide (NO) is known to have a very short half-life, and it is oxidized to nitrate (NO 3 − ) and nitrite (NO 2 − ). The activity and/or expression of nitric oxide synthases (NOSs) can change in response to toxins or therapeutic medications. For example, in recent studies in our laboratory and others, it has been reported that the amount of NO was increased in the serum of N-nitroso compounds-treated animals. N-nitroso compounds, which are found in different types of foodstuffs, including meat, salted fish, alcoholic beverages, agricultural drugs, insecticides, cigarettes, and several vegetables, are known to have carcinogenic effects. In addition, it is experimentally used to induce liver carcinoma to study the mechanisms of liver cytotoxic injury. Uncontrolled, prolonged, and/or massive production of NO by inducible NOS may cause liver damage, inflammation, and even tumor development during N-nitroso compound toxicity. In this chapter, we explain the roles of NOS and NO in various toxicity conditions, such as toxicity in environment pollutant or food additive, and present the evaluation of the toxicity and the importance of NOSs in human health.

Thiols: Role in Oxidative Stress-Related Disorders

“…Nitric oxide is produced during the reaction which arginine is converted to citrulline catalyzed by nitric oxide synthase (NOS) which is NADPH-dependent enzyme [36,37]. There are three isoforms of NOS: neuronal (nNOS) endothelial (eNOS) and inducible (iNOS) and it is known to be present in every cell component [17,38]. NO is an uncharged lipophilic molecule containing unpaired electron.…”

“…Most of its direct physiological effects are cyclic guanosine 3′,5'monophosphate-mediated (cGMP). It can also interact with proteins containing iron and zinc or create S-nitrosothiols through nitrosylation [2,[13][14][15][16][17]. Many antioxidants work in the organism to prevent damage caused by ROS and RNS.…”

Carcinogenic effects of N-nitroso compounds in the environment

“…It is determined that the metabolism of DMN is done by the cytochrome P-450 monooxygenase enzyme which further initiates their toxic effects. So, instead of their excretion with urine, they initiate the onset of necrosis, cancer, and mutations through the formation of a covalent bond with the biomolecules (Atakisi and Merhan, 2017). There is a direct association between the synthesis of N-nitroso compounds with the help of bacteria and raised risk for nasopharynx, esophagus, stomach, and liver cancer (Kamangar et al, 2010).…”

“…There is a direct association between the synthesis of N-nitroso compounds with the help of bacteria and raised risk for nasopharynx, esophagus, stomach, and liver cancer (Kamangar et al, 2010). The toxic effects of Diethylnitrosamine and other N-nitroso compounds can be decreased by the administration of antioxidant molecules such as αlipoic acid, beta-carotene, blueberry, omega-3 and other secondary metabolites (like tannins, terpenoids, alkaloids, glycosides, and phenols) procured from the medicinal plants (Atakisi and Merhan, 2017;Jain et al, 2020;Prakash et al, 2019;Razzak et al, 2020;Verma et al, 2020).…”

Biochemical and Pharmacological Properties of Biogenic Amines

“…The pharmacological effects of putrescine, cadaverine, spermine, and spermidine are at lower levels according to histamine, tyramine, and phenylethylamine [77]. Putrescine, causing hypotension, bradycardia, and lockjaw, creates carcinogenic heterocyclic compounds including nitrosamine, nitrosopyrrolidine, and nitrosopiperidine as some biogenic amines such as cadaverine, spermine, and spermidine react with the nitrite [5,10,39,78].…”