Pakistan J. Zool., vol. 47(4), pp. 1109-1116, 2015. Effect of STZ-Induced Diabetes on Spleen of Rats: Improvement by Camel Whey Proteins Hossam Ebaid, 1,2 * Jameel Al-Tamimi, 1 Ali Metwalli, 3,4 Ahmed Allam, 1,5 Kairy Zohir, 6 Jamaan Ajarem, 1 Ahmed Rady, 1 Ibrahim M. Alhazza 1 and Khaled E. Ibrahim 1 1 Department of Zoology, College of Science, King Saud University, Riyadh, KSA 2 Department of Zoology, Faculty of Science, El-Minia University, El-Minia, Egypt 3 Department of Food Science, College of Agriculture and Food Science, King Saud University, Riyadh, KSA 4 Department of Dairy, Faculty of Agriculture, El-Minia University, El-Minia, Egypt. 5 Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 65211, Egypt. 6 Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, KSA Abstract.- Diabetes is the most prevalent disease, and the number of people affected by this disease is still increasing. This study was conducted to assess the effect of whey proteins (WPs) on the spleen tissues of diabetic rats. Data showed that a significant decrease in the total body weight was recorded in diabetic animals compared with the non-diabetic control ones. The extent of this weight loss was significantly less in the WP–treated diabetic group. Relative spleen weight in the diabetic animals revealed that splenic atrophy was more pronounced compared to those of control ones. Results showed that diabetes significantly up-regulated both the reactive oxygen spices FMO2 mRNA and Fas mRNA when compared with the control animals. Light microscopy showed white pulps that were greatly diffused with highly distributed trabeculae in the spleen tissue of diabetic rats. Moreover, Perl’s Prussian blue staining revealed impaired phagocytic activity in diabetic animals. Interestingly, feeding diabetic animals on WPs successfully restored the histological integrity of their spleens. Furthermore, induced diabetes was found to significantly up- regulate both reactive oxygen spices, FMO2 mRNA and Fas mRNA in diabetic animals compared to the control ones. In addition, WPs were found to significantly down-regulate the Fas mRNA in both control and diabetic animals. In conclusion, the current study proved that WPs restored the oxidative stability and the splenic structural integrity and activity, which may be proposed as natural candidates for the treatment of diabetes and oxidative stress. Key words: Spleen, Whey proteins, FMO2, oxidative stress, diabetes. INTRODUCTION Diabetes is the most prevalent disease in the Kingdom of Saudi Arabia (KSA), where the number of people affected by this disease is still increasing. Type 1 diabetes (T1D) is caused by autoimmune destruction of insulin-producing ß- cells. In this process, ß-cell apoptosis involves multiple signaling cascades stimulated by interleukin-1beta (IL)-1β, interferon-gamma (IFN- γ), and tumor necrosis factor-alpha (TNF-α) (Faloon et al., 2011). Whey proteins (WPs) contain several biologically active components, including lactoerrin, beta-lactoglobulin, alpha-lactalbumin, glycomacro- peptide, and immunoglobulins. Therefore, it demonstrates a range of immune-enhancing ___________________________ * Corresponding author: hossamebaid@yahoo.com 0030-9923/2015/0004-1109 $ 8.00/0 Copyright 2015 Zoological Society of Pakistan properties in diabetes (Ebaid, 2014a). The primary mechanism by WPs is thought to exert its effects by intracellular conversion of the amino acid cysteine to glutathione, a potent intracellular antioxidant (Bounous et al., 1988, 1989; Ebaid et al., 2012). A number of clinical trials have successfully been performed using WPs in the treatment of cancer, HIV, hepatitis B, cardiovascular disease, osteoporosis, and as an antimicrobial agent (Marshall, 2004). Spleen represents a large lymphatic tissue passed by re-circulating lymphocytes, which are able to promptly elicit specific T or B lymphocyte- mediated immune reactions. This study was designed to assess the effect of WP on the spleen tissues following diabetes. __________________________________________ Abbreviations: CMC, Carboxymethyl cellulose; Fas, Programmed cell death- receptor; H&E, Haematoxylin-eosin; IFN-γ, Interferon gamma; IL-6, Interleukin 6; MTT, Cell proliferation assay; STZ: Streptozotocin; TNF-α, Tumour necrosis factor-alpha; WPs: