Abstract
Nitrites and morpholine are ubiquitous environmental contaminants found in drinking water and food. NMOR can be formed endogenously from nitrite and morpholine. Increased levels of reactive oxygen species/ reactive nitrite species (ROS/RNS) are involved in the mechanism of NMOR toxicity. Certain antimicrobial, antifungal and antioxidant potential were observed in heterocyclic benzimidazole derivatives and dimethyl sulfoxide (DMSO). This study was designed to evaluate the biological potential of 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile in the protection of lung and colon tissues against the increased levels of ROS/RNS that are induced by administration of nitrite and morpholine in drinking water for 15 weeks. Forty adult male rats were categorized into 4 groups, 10 rats each. The results showed a significant increase in NO, lipid peroxidation (LPO), total peroxides (TPO), superoxide anion (O2-) and DNA fragmentation in lung and colon tissues of rats treated with nitrite and morpholine compared to the control group. Moreover, histological observation of the lung and colon tissues showed cell necrosis, increase in the leukocyte infiltration and blood vessel congestion. Immunostaining for inducible nitric oxide synthase (iNOS) showed positive reaction for lung and colon tissues. After the co-treatment of rats with DEMSO and 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile, all the previous biochemical changes were reduced in addition to the relative improvement in the morphological changes of both lung and colon. In conclusion, the injury in lung and colon tissues induced by nitrite and morpholine may return to the increased production of ROS and to the alterations in the levels of antioxidants. Co-treatment of rats with 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile and DMSO may protect them against nitrite and morpholine toxicity. Key words: Nitrite, morpholine, nitrosomorpholine (NMOR), inducible nitric oxide synthase (iNOS), benzimidazole derivatives, dimethyl sulfoxide (DMSO), colon, lung, rat.
Highlights
The importance of considering chemical mixture exposure in dealing with environmental issues has recently become better recognized
The present study was designed to evaluate the biological activity of the 3aminothiazolo[3-2a]benzimadzole-2-carbonitrile and its solvent dimethyl sulfoxide (DMSO), in the protection of lung and colon tissues against oxidative stress induced by nitrite and morpholine as precursor of NMOR and to evaluate the role of inducible nitric oxide synthase in NMOR toxicity
When 3aminothiazolo[3-2a]benzimadzole-2-carbonitrile or its solvent DMSO was given to sodium nitrite and morpholine administered rats, they significantly inhibited the increase of lipid peroxidation (LPO), Nitric oxide (NO), total peroxides (TPO) and O2- in colon and DNA fragmentation percent in lung and colon
Summary
The importance of considering chemical mixture exposure in dealing with environmental issues has recently become better recognized. Nitrites and secondary amines which represent precursors of NNC are contained in many kinds of common food and can react under acidic conditions in the stomach (Erkekoglu and Baydar, 2010). NMOR and their precursors in the environment in certain occupational location as well as their endogenous formation in the human body from dietary components are associated with an increased risk of gastrointestinal cancer (Hord et al, 2009). The present study was designed to evaluate the biological activity of the 3aminothiazolo[3-2a]benzimadzole-2-carbonitrile and its solvent DMSO, in the protection of lung and colon tissues against oxidative stress induced by nitrite and morpholine as precursor of NMOR and to evaluate the role of inducible nitric oxide synthase (iNOS) in NMOR toxicity
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