Zinc improves antioxidative enzymes in red blood cells and hematology in lithium-treated rats Anshoo Malhotra, Devinder K. Dhawan ⁎ Department of Biophysics, Panjab University, Chandigarh 160014, India Received 29 June 2007; revised 5 October 2007; accepted 9 November 2007 Abstract The present study was designed to evaluate the protective role of zinc in attenuating the adverse effects induced by lithium in blood of female Wistar rats. Female Wistar rats received lithium in the form of lithium carbonate in diet at a dose level of 1.1 g/kg diet, zinc alone in the form of zinc sulfate in drinking water at a dose level of 227 mg/L drinking water, or lithium plus zinc treatments in the combined group for a total duration of 2 months. Effects of the treatments were studied on antioxidant defense system, various hematologic parameters, and percentage of 65 Zn-specific activity. Lithium treatment resulted in a significant increase in lipid peroxidation levels but caused a significant decrease in reduced glutathione levels and the activities of catalase, glutathione S-transferase, and superoxide dismutase. Lithium treatment also caused a significant decrease in the activities of aminolevulinic acid dehydratase and Na + K + adenosine triphosphatase. However, it resulted in a significant increase in total leukocyte counts, neutrophils, and lymphocyte counts as well as zinc protoporphyrin levels, whereas a significant decrease in counts of monocytes, eosinophils, and percentage specific activity of 65 Zn in blood and its various fractions was noticed. Furthermore, lithium treatment caused a significant decrease in serum zinc levels. However, zinc supplementation to lithium-treated rats effectively raised the reduced glutathione levels and also normalized lipid peroxidation and the activities of antioxidative enzymes, which included catalase, glutathione S-transferase, and superoxide dismutase. Moreover, zinc supplementation could raise the activities of the enzymes aminolevulinic acid dehydratase and Na + K + adenosine triphosphatase as well as the percentage uptake values of 65 Zn in blood and its fractions. The study suggests that zinc, as a nutritional supplement, has the potential in attenuating most of the adverse effects induced by lithium in rat blood. © 2008 Elsevier Inc. All rights reserved. Keywords: Lithium; Zinc; ALAD; ZPP; Rats 1. Introduction Lithium is being used worldwide as an important drug in the treatment of mental disorders especially in mania and in the prophylaxis of bipolar manic-depressive psychosis [1]. Lithium is considered to affect metabolism, neuronal communication, and cell proliferation [2]. Lithium effects have been investigated in detail on the brain, intestine, thyroid, and liver functions [3-9]. Lithium has also been reported to affect the synthesis, activation, and inactivation of various neurotransmitters such as norepinephrine, ser- otonin, and dopamine [10]. During lithium therapy, a significant decrease in the levels of zinc in serum has been reported [11]. Lithium treatment has been shown to affect membrane dynamics of red blood cells (RBCs) [12] as well as to cause an increase in total leukocyte counts (TLCs) [13]. Zinc is an essential trace element as well as a micronutrient that is required for a broad range of biologic activities and is nontoxic with the exception of a very high dose [14]. Zinc is a fundamental element of more than 200 Available online at www.sciencedirect.com Nutrition Research 28 (2008) 43 – 50 www.elsevier.com/locate/nutres ⁎ Corresponding author. E-mail address: dhawan@pu.ac.in (D.K. Dhawan). 0271-5317/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.nutres.2007.11.002