N‐nitrosodimethylamine changes the expression of glutathione S‐transferase in the liver of male mice: The role of antioxidants

Abstract

The present study investigated the protective effect of gossypol, selenium, zinc, or glutathione (GSH) against dimethylnitrosamine (DMN)-induced hepatotoxicity in the livers of male mice. The expression and the activity of glutathione S-transferase (GST), levels of GSH, and free radicals (malondialdehyde (MDA)), as well as the activity of glutathione reductase were determined after the treatment of mice for seven consecutive days with low or high doses of gossypol, selenium, zinc, or GSH. In experimental groups, DMN was administered as a single dose for 2 h after the repeated dose treatments of mice for seven consecutive days with each antioxidant. DMN reduced the expression and inhibited the activity of GST. However, repeated treatments of mice with low-dose gossypol or high dose of either selenium or GSH followed by a single dose of DMN induced the expression and the activity of GST. In contrast, low-dose treatments of mice with zinc, selenium, or GSH followed by a single dose of DMN reduced the expression and the activity of GST compared to either control or DMN-treated groups. In addition, high-dose treatment with either gossypol or selenium markedly induced the levels of GSH compared to either control or DMN-treated groups. Interestingly, pretreatment of mice with high dose of either gossypol or selenium for seven consecutive days followed by a single dose of DMN decreased the levels of MDA, whereas DMN induced such levels. It is concluded that high dose of either gossypol or selenium is a stronger protector than zinc and GSH in ameliorating the toxic effects of DMN.

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

“…In addition, the level of GSH was increased after treatment of rats with all tested N-nitrosamines (Table 2). It is taught that increment in GSH might be due to induction of GSH synthase and gamma-glutamyltransferase [63–65]. However, in the present study, the increased level of GSH was found to be dependent on the activity of GR since the activity of GR was also potentially induced after treatment of rats with N-nitrosamines (Table 2).…”

N‐nitrosamines induced infertility and hepatotoxicity in male rabbits

“…N‐nitrosamines are mainly metabolized by cytochrome P450 2E1 at a greater extent in the liver than any other organs into more toxic alkylating agents that bind covalently with DNA and other macromolecules . The toxicity of the alkylating agents could be alleviated after induction of GST activity and enhancement of GSH levels . Therefore, inducers of GSTs are generally considered as protective agents against toxicity of various toxic compounds including N‐nitrosamines.…”

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 ].…”