Content and Redistribution of Vitamin E in Tissues of Wistar Rats Under Oxidative Stress Induced by Hydrazine

Abstract

Hydrazine toxicity is associated with generation of several kinds of free radicals and oxidative stress in cell. Experiments in vivo have demonstrated that oxidative stress could either diminish or increase concentration of vitamin E in some tissues. Thus in the present study we performed experiments to determine whether hydrazine-induced oxidative stress would change the tissue levels of the vitamin. Seven days of hydrazine intoxication led to accumulation of different amounts of vitamin E: 215% in the liver, 118% in the heart, 135% in the spleen, and 100% in the muscle over control value. There were no changes in the level of the vitamin in kidney and pancreas, despite its significant depletion in the serum. In tissue that accumulated vitamin E after hydrazine treatment, an increased of oxidative stress measured by the concentration of lipid-soluble fluorophore was observed. Significant increases of 107%, 46%, 72%, and 58% over control values were observed in the liver, heart, spleen, and muscle, respectively. Rats treated with hydrazine and pharmacological doses of alpha-tocopherol accumulated higher concentrations of vitamin E in all studied tissues compared with the alpha-tocopherol-only treated rats. However, in tissues with elevated levels of fluorophore as liver, heart, spleen, and muscle, the accumulation of vitamin E was 5.03, 4.5, 4.03, and 4.6 times higher than in alpha-tocopherol-treated rats, respectively. Vitamin E concentration was much higher than in kidney and pancreas, where the accumulation was only 2.31 and 2.6 times higher. On the other hand, 3 days of hydrazine treatment did not change either the level of lipid-soluble fluorophore or the level of vitamin E in the liver mitochondria, microsomes, and homogenate. In skeletal muscle vitamin E caused decreased lipofuscin accumulation, and in pancreas vitamin E increased lipofuscin accumulation. Our data indicate that hydrazine is able to modify significantly vitamin E status in different rat tissues.

Current Development of Thiazole-Containing Compounds as Potential Antibacterials against Methicillin-Resistant Staphylococcus aureus

“…Hydrazine is an essential active unit for the antibacterial activity of phenylthiazole compounds, as discovered by Hagras et al Hydrazine and hydrazine-containing groups were considered to be toxic and could produce the corresponding toxic diazo intermediates and increase the incidence of oxidative stress in living tissues. − Hence, the hydrazine moiety is an uncommon structural motif in approved therapeutics, such as isoniazid. Compounds with toxic structures like isoniazid also carry a black box warning due to acute hepatotoxicity .…”

Development of Biphenylthiazoles Exhibiting Improved Pharmacokinetics and Potent Activity Against Intracellular Staphylococcus aureus

“… Lastly, intensive efforts were reported to optimize the cationic part, in which the hydrazine moiety potentiates the antibacterial activity (Figure ). Hydrazine and hydrazine-like structures are considered toxicophores that increase the incidence of oxidative stress in living tissues. , Hence, hydrazine moiety is an uncommon structural motif in approved therapeutics, and those containing such toxic moiety, isoniazid as an example, are associated with a black box warning due to acute hepatotoxicity . Hydrazine-containing structures exert their toxic effect via metabolic activation into diazonium derivative and subsequent generation of aryl free radicals .…”