Int. J. Pharm. Sci. Rev. Res., 38(2), May – June 2016; Article No. 40, Pages: 219-226 ISSN 0976 – 044X International Journal of Pharmaceutical Sciences Review and Research Available online at www.globalresearchonline.net © Copyright protected. Unauthorised republication, reproduction, distribution, dissemination and copying of this document in whole or in part is strictly prohibited. 219 Farouk K. El-Baz* 1 , Wagdy K. B. Khalil 2 , Hoda F. Booles 2 , Hanan F. Aly 3 , Gamila H. Ali 4 1 Plant Biochemistry Department, National Research Centre (NRC), 33 EL Bohouth st. (former EL Tahrir st.), Dokki, Giza, Egypt. 2 Cell Biology Department, National Research Centre (NRC), 33 EL Bohouth st. (former EL Tahrir st.), Dokki, Giza, Egypt. 3 Therapeutic Chemistry Department, National Research Centre (NRC), 33 El Bohouthst. (former El Tahrir st.), Dokki, Giza, Egypt. 4 Water pollution Research Department, National Research Centre (NRC), 33 El Bohouth st. (former El Tahrir st.), Dokki, Giza, Egypt. *Corresponding author’s E-mail: fa_elbaz@hotmail.com Accepted on: 10-05-2016; Finalized on: 31-05-2016. ABSTRACT The aim of the present investigation is to study the protective effect of the Dunaliella slina extract against streptozotocin (STZ)- induced type 2 diabetes mellitus (T2DM) in male rats. Paraoxonase-1 (PON1), transforming growth factor-β (TGF-β), apoptosis assay as well as expression of the apoptosis and inflammatory related genes were assessed. The results revealed that the antioxidant biomarker PON1 decreased in diabetic rats, however, TGF-β level was elevated in diabetic rats. Whereas, the treatment of rats with STZ increased the apoptosis rates and the alterations of the pro-apoptosis (Eotaxin, Caspase-1 and Caspase-2) as well as inflammation (NF-κ β1 and AIF-1) related genes. Aside from, treatment of diabetic rats with D. salina ethanolic extract, they demonstrated an increase in PON1 level, while reduction in the elevated TGF-β level was monitored. However, treatment of STZ- injected rats with D. salina extract exhibited low apoptosis rates and decreased the alteration of the pro-apoptosis and inflammatory related genes induced by STZ in rats. The biological effect of D. salina could be attributed to its high level of 9-cis - carotene which protect cells from the oxidative stress, hence, treatment of diabetic rats with D. salina extract declared therapeutic potential in hyperglycemia dominance which need further clinical trial for usage as nutraceutical product, in diabetic regimen. Keywords: Dunaliella slina, type 2 diabetes mellitus, Paraoxonase-1, transforming growth factor-β, apoptosis. INTRODUCTION iabetes mellitus (DM) is a global health problem that will rise in the following twenty years, with special hazards due to the increase number of diabetic patients in children and adolescents categories. 1 Paraoxonase (PON), an enzyme linked to high-density lipoprotein (HDL), intones both roles of antioxidant and anti-inflammatory of HDL beside it may have a protective role in the prevention of these complications. 2 Low activity of PON1 has been detected in diabetic status associated with high tendency for cardiovascular attack, as PON1 activity is dependent contributing risk factor for coronary artery disease. 3 Chronic and low-grade inflammations are related to type 2 diabetes where, pro- inflammatory and anti-inflammatory cytokines are released mainly by the adipose tissue. 4 Among these cytokines, transforming growth factor-β (TGF-β) which is played the central role in inflammatory process in T2DM. 4 TGF-β1, acts as anti-inflammatory immunemediator, inhibits or reverses the macrophages activation by interfering with signaling throughout toll-like receptor- dependent pathways. High levels of TGF-β1 and interleukin-1 receptor antagonist (IL-1Ra) were accompanied with T2DM, leading to diabetic complication hence, TGF-β1 may act in both sides. 5 Reactive oxygen species (ROS) induced by drugs such as anticancer drugs lead to considerable cellular damage and to a point of no return in apoptosis. 6 In the model of STZ-mediated hyperglycemia, the hydroxyl (OH), reactive oxygen species (ROS), acts as a reactive intermediate initiating liver apoptosis. 7 The authors declared that, OH radicals increased in the diabetic rats liver play a serious role in the elevation of hepatic lipid peroxidation (LPO), leading to increment in pro-apoptotic events. Apoptosis, or programmed cell death, is a physiological process, genetically controlled and it essential for normal tissue development and homeostasis. Eotaxin gene is one of the pro-apoptotic genes and it is encoding protein belong to cytokines. A recent study reported that eotaxin is a ligand for C-C chemokine receptor type 5 (CCR5) may explain the macrophage accumulation that occurred at 24 h. 8 However, infiltrating leukocytes may often be sources of pro-inflammatory chemokines, and it is more likely that the delayed recruitment of macrophages into the tissue reflects secondary processes dependent upon the induction of other chemokines rather than being dependent directly upon the action of eotaxin or eotaxin-2. One of the best-known the mediators of apoptosis are caspases, which are cysteine-dependent, aspartate- specific proteases involved in pro-inflammatory cytokine activation and are the effectors of apoptotic pathways. 9 Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Grant and Dixit 10 reported that, caspase-1 controls the secretion of bioactive IL-1β throughout some, a multiprotein that is composed of NLRP3 (nucleotide-binding domain, leucine- rich-containing family, pyrin domain-containing-3) ASC Dunaliella salina Suppress Oxidative Stress, Alterations in the Expression of Pro-Apoptosis and Inflammation Related Genes Induced by STZ in Diabetic Rats D Research Article