Effect of Icariin in Diabetic Rats With or Without Experimentally Induced Chronic Kidney Disease

Diabetes mellitus (DM) is a prevalent chronic non-communicable disease that poses a significant health burden worldwide. It causes a number of macrovascular and microvascular complications. Chronic kidney disease (CKD) is one of the major and morbid complications of DM. CKD is a significant public health problem worldwide with a high prevalence of morbidity and mortality. It is hypothesized that elevated intracellular glucose levels contribute to the generation of reactive oxygen species, which subsequently disrupts several downstream pathways, including the activation of protein kinase C and the activation of advanced glycation end products. This induces several pathways of inflammation, oxidative stress and apoptosis. Herbal agents that possess anti-inflammatory and antioxidative properties could be studied as adjunctive therapy for patients with DM and CKD Icariin (ICA), a flavonoid compound derived from the herb Epimedium brevicornum Maxim, has demonstrated wide pharmacological effects in many in vivo and in vitro studies, including osteoporosis, cancer, inflammation, neurodegenerative diseases, cardiovascular diseases and diabetes. In diabetic rat models, ICA has been shown to improve diabetes retinopathy and early diabetic nephropathy. ICA has also demonstrated its protective effects against nephrotoxicity in various animal models. However, the effects of ICA on diabetic rats with adenine-induced CKD have not been investigated. Therefore, this study aims to investigate the effect of ICA on adenine-induced CKD in STZ-induced diabetics in rats. To the best of our knowledge, the effect of ICA on such widely used diabetic and CKD model has not been studied before. Diabetes will be induced in rats by injection of streptozotocin, and CKD by adenine (0.25% w/w, 4 weeks). This is a valid and reliable animal model of human CKD. Various measurements and parameters will be used to establish the effect of ICA on DM with CKD. These include physiological measurements such as changes in body and kidneys weight, water intake and fecal and urine output; biochemical measurements such as urea, creatinine, creatinine clearance; oxidative and nitrosative, inflammatory parameters such as interleukin-6, interleukin-10, interleukin-1? and tumor necrosis factor-?; histopathological studies; and Western blotting techniques.