Protective effect of L-ascorbic acid on nickel induced pulmonary nitrosative stress in male albino rats Shaheenkousar H. Hattiwale Sikha Saha Saeed M. Yendigeri Jameel G. Jargar Salim A. Dhundasi Kusal K. Das Received: 18 October 2012 / Accepted: 24 February 2013 / Published online: 6 March 2013 Ó Springer Science+Business Media New York 2013 Abstract Nickel sulfate stimulates inducible nitric oxide synthase (i-NOS) and increases serum nitric oxide concentration by overproduction of reactive nitrogen species due to nitrosative stress. The present study was undertaken to assess possible protective role of L-ascorbic acid as an antioxidant against nickel induced pulmonary nitrosative stress in male albino rats. We studied the effect of the simultaneous treatment with L-ascorbic acid (50 mg/100 g b. wt.; orally) and nickel sulfate (2.0 mg/100 g b. wt.; i.p.) on nitric oxide synthesis by quantitative evaluation of serum i-NOS activities, serum and lung nitric oxide, L-ascorbic acid and protein concentrations of Wister strain male albino rats. We have further studied histopathological changes in lung tissue after nickel sulfate treatment along with simultaneous exposure of L-ascorbic acid. Nickel sulfate treatment significantly increased the serum i-NOS activity, serum and pulmonary nitric oxide concentra- tion and decreased body weight, pulmonary somatic index, serum and lung L-ascorbic acid and protein concentration as compared to their respective controls. Histopathological changes induced by nickel sulfate showed loss of normal alveolar architecture, inflamma- tion of bronchioles, infiltration of inflammatory cells and patchy congestion of alveolar blood vessels. The simultaneous administration of L-ascorbic acid and nickel sulfate significantly improved all the above biochemical parameters along with histopathology of lung tissues of rats receiving nickel sulfate alone. The study clearly showed a protective role of L-ascorbic acid against nickel induced nitrosative stress in lung tissues. Keywords Nickel sulfate Á i-NOS activity Á Nitrosative stress Á Lung histopathology Á L-ascorbic acid Introduction Some heavy metals have bio-importance as trace elements but, the toxic effects of many of them in human biochemistry are of great concern (Duruibe et al. 2007). The vast industrial use of nickel has led to the environmental pollution by metal and its by-prod- ucts during production, recycling, and disposal. Nickel is a known hematotoxic, immunotoxic, hepatotoxic, pulmotoxic, and nephrotoxic agent (Das and Buchner 2007). Several heavy metals including nickel have S. H. Hattiwale Á J. G. Jargar Á S. A. Dhundasi Á K. K. Das (&) Environmental Health Research Unit, Department of Physiology, Al Ameen Medical College, Bijapur 586108, Karnataka, India e-mail: kusaldas@yahoo.com S. Saha Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, Faculty of Medicine & Health, University of Leeds, Leeds LS2 9JT, UK S. M. Yendigeri Department of Pathology, Al Ameen Medical College, Bijapur 586108, Karnataka, India 123 Biometals (2013) 26:329–336 DOI 10.1007/s10534-013-9617-3