Effects of Diabetogenic Agent Streptozotocin on Hematological Parameters of Wistar Albino Rats "An Experimental Study"

Background: Diabetes mellitus has remained the major concern for medical sciences researches due to its deleterious effects on general, physical and mental health of patients. To understand the pathophysiology and to explore better treatment options for such kind of metabolic disorders it is necessary to generate the experimental animal models. To create diabetic animal models, streptozotocin has shown predominance in selectivity as a diabetogenic agent. While studying effects of any intervention in the diabetic animal models, being a cytotoxic drug streptozotocin may affect the study results by inhibiting highly replicating cells especially hematopoietic cells. Keywords: Streptozotocin; animal model; hematological parameters. 1. INTRODUCTION Diabetes mellitus has remained the major concern for medical sciences researches not only due to its high incidence and prevalence rate but also due its deleterious effects on general, physical and mental health of the patients [1]. To understand the pathophysiology and to explore better treatment options for such kind of metabolic disorders it is necessary to generate the experimental animal models [2]. To create diabetic animal models, surgical (pancreatectomy) and pharmacological (alloxan monohydrate and streptozotocin) options have been used in research but pharmacological options particularly use of streptozotocin has shown predominance in selectivity as a diabetogenic agent [1,2]. Chemically, streptozotocin is a derivative of synthetic Nitrosoureido Glucopyranose and has been used for cancer chemotherapies [3], being its potential to inhibit DNA synthesis in bacterial and mammalian cells [4]. While its diabetogenic effect is thought to be attributed to its ability to cause pancreatic β cells’ death by DNA alkylation and hence used to induce diabetes mellitus in experimental animals [5,6]. The methods to induce diabetes in animal models by streptozotocin fall under three categories 1. Multiple small doses (i.e. 40 mg/kg) of streptozotocin over a period of several days 2. A single moderate dose (i.e. 60 mg/kg) of streptozotocin or 3. A single large dose (100 mg/kg) of streptozotocin produce diabetes in 48- 72 hours. Usually a single large dose of streptozotocin is used to induce diabetes in experimental models as reported by Ito et al. 100 mg / kg of streptozotocin produced non-insulin dependent diabetes mellitus in experimental animals [7]. Streptozotocin can be administered by various routes including subcutaneous and intramuscular routes but intraperitoneal and intravenous administration routes are preferred. [8]. After 3-4 days of streptozotocin administration fasting blood glucose levels are obtained to confirm the accuracy of procedure [9] and on 5th day when 180-500 mg/dl serum glucose levels are obtained experimental animals are considered as diabetic [10]. Though streptozotocin is preferred pharmaco- logical method for induction of diabetes [11], many studies have reported spontaneous recovery from hyperglycemia due to reactive hyperinsulinemia insulinoma [12,13,14]. Streptototozin, not only affects pancreas and cause diabetes in experimental animals but also have a potential to produce toxic effects on other body tissues as well. It has been learnt through a number of studies that streptozotocin is associated with high incidence of hepatic and renal tumors [15], increase in permeability of blood brain barrier [16], renal hypertrophy [17] and retinal damage in experimental animal models [18]. As already discussed that streptozotocin damages DNA by alkylation and produces free radicals, therefore it may harm any organ system of animals [19]. Despite of aforementioned, streptozotocin is still employed Aims: The aim of study was to analyze the effects of streptozotocin on various cellular components of blood such as RBCs, WBCs (Lymphocytes, Neutrophils, Eosinophils), Hb%, HCT and Platelets, at baseline, 5th day and 15th day without any intervention. Study Design: Animal based Experimental study. Place and duration of Study: The study was conducted at animal house of faculty of Pharmacy Ziauddin University Karachi, while laboratory work was performed at MDRL-1 Ziauddin University. Methodology: In Group A normal saline and in group B and C 60 mg / kg streptozotocin diluted in normal saline was administered intraperitoneally. After the confirmation of induction of Diabetes in rats, on fifth day blood samples were drawn from Group A and B and were analyzed. While blood samples from group C were drawn on fifteenth day. Results: Analysis of various hematological parameters on 5th day revealed that there was a decrease in the levels of Hb, HCT, RBCs and WBCs with an increase in platelet count in group B in comparison to group A (control). On the other hand, in Group C (15th day), blood cell counts (Hb, HCT, RBCs, WBCs, Lymphocytes, Neutrophils and platelets) seemed to recover from streptozotocin induced decline that was observed in group B, however did not reach the baselines as in group A(control). Conclusion: It is concluded that change in hematological parameters of rats after administration of streptozotocin is reversible. The blood parameters may recover near to base line values without any intervention within two weeks.