Abstract
Serum and liver selenium levels were studied during the pathogenesis of N-nitrosodimethylamine (NDMA) induced hepatic fibrosis in rats. The degree of fibrosis was assessed with Masson’s trichrome staining and quantifying collagen content in the liver. Lipid peroxides were measured in blood and liver samples and total glutathione and glutathione peroxidase were assayed in the liver tissue to evaluate oxidative stress. Interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) were measured in the serum. Selenium levels were determined using inductively coupled plasma-mass spectrometry (ICP-MS) after acid digestion and hydride generation of selenium. Serial administrations of NDMA produced well-developed fibrosis and early cirrhosis in the liver with 4-fold increase of total collagen content and deposition of collagen fibers. Blood and hepatic lipid peroxides, serum IL-6 and TGF-β1 were significantly increased. There was significant reduction in hepatic glutathione and glutathione peroxidase levels. Serum and liver selenium were remarkably decreased on all the days studied. The results suggest that decreased selenium and glutathione peroxidase contribute to the impairment of cellular antioxidant defense, which in turn results in oxidative stress and trigger pathogenesis of hepatic fibrosis. The study further demonstrated that ICP-MS with hydride generation technique is a reliable and sensitive method for determination of selenium in biological samples.
Acknowledgments
The author is thankful to Dr. C. K. Mathews, Director, Chemical Group, Indira Gandhi Center for Atomic Research (IGCAR), Kalpakkam, Tamil Nadu, India for his permission to use the PerkinElmer SCIEX ELAN Inductively Coupled Plasma-Mass Spectrometer for the measurement of selenium. The technical assistance of Dr. Lisa George and Ms. S. Vijayalakshmi, Chemical Group, IGCAR, Kalpakkam is gratefully acknowledged. This work was supported by the Indian Council of Medical Research (Funder Id: 10.13039/501100001411), New Delhi, India, by grant no. 3/1/2/3/(9201540)/92-NCD-III to the author.
Conflicts of interest statement: The author does not have any conflicts of interest to declare in connection with this article.
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