Novel Study on N-Nitrosamines as Risk Factors of Cardiovascular Diseases

Abstract

Millions of people are exposed daily to N-nitrosamines from different environmental sources. The present study aims at investigating the role of N-nitrosamines in the alteration of homocysteine, lipid profile, oxidative stress, paraoxonase activity, antioxidant enzymes, and free radicals which are important risk factors for CVD. In addition, biomarkers of cardiovascular diseases such as creatine kinase MB activity (CK-MB) and lactate dehydrogenase (LDH) as well as protein expression of both glutathione peroxidase and glutathione S-transferase π isozyme were assayed after treatment of rats with 0.2 mg/kg body weight of N-nitrosodibutylamine (NDBA), N-nitrosoethylbutylamine (NEBA), N-nitrosobutylpropylamine (NBPA), N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), and N-nitrosodiphenylamine (NDPA) as a daily dose for two weeks. LDL levels, paraoxonase activity, reduced glutathione levels, and glutathione reductase activities were increased, whereas HDL levels decreased after treatment of rats with most of N-nitrosamines compared to control group. Moreover, levels of free radicals and catalase activity increased, whereas protein expression of both glutathione peroxidase and glutathione S-transferase decreased after treatment of rats with some N-nitrosamines. The data showed that most N-nitrosamines increased CK-MB and LDH activities. It is concluded that N-nitrosamines increased levels of free radicals, and decreased the activity of antioxidant enzymes which may consequently increase the incidence of CVDs.

N‐nitrosamines induced infertility and hepatotoxicity in male rabbits

“…The second, third, fourth, and fifth group received 0.5 mg/kg BW of methyethylnitrosamine, (MEN), diethylnitrosamine (DEN), diphenylnitroasamine (DPN) and dimethylnitrosamine (DMN) respectively as a daily dose for 12 weeks. All compounds were dissolved in distilled water and the administered doses were selected according to Sheweita et al, (2014)…”

“…N‐nitrosamines are known to be hepatic carcinogens in different animal species and are metabolized by the liver microsomal enzymes including cytochrome P‐450 system leading to biologically active derivatives . N‐nitrosamines and/or their metabolites can interact with cellular DNA to form a broad spectrum of DNA adducts . It is thought that DNA alkylation can be a critical event in cancer induction .…”

Cnidoscolus aconitifolius leaf extract and ascorbate confer amelioration and protection against dimethyl nitrosamine-induced renal toxicity and testicular abnormalities in rats

“…Nitrosamines which include DMN and diethyl nitrosamine (DEN) have been widely reported to stimulate or initiate oxidative stress and tissue destruction via the production of free radicals, which are released during the metabolism of nitrosamines by the cytochrome P 450 enzymes, forming reactive electrophiles [ 62 , 63 ]. Due to the instability of these ROS, they attack the electron rich components of cell membranes, thereby destroying the cells and altering cellular functions [ 64 , 65 ].…”

Cigarette- and snus-modified association between unprotected exposure to noise from hunting rifle caliber weapons and high frequency hearing loss. A cross-sectional study among swedish hunters

“…Tobacco contains, apart from nicotine, different types of TSNAs. [14282930] TSNAs are mainly known as potent carcinogens,[31] by damaging the cell's deoxyribonucleic acid (DNA). [32] This cytotoxic effect can be potentiated in cell cultures by free radicals.…”