Effect of different combination of flaxseeds, melatonin, gum acacia and betaine in diabetic rats with experimentally- induced chronic kidney disease

Diabetes mellitus (DM) is a well-known chronic metabolic disease that is strongly related to macrovascular and microvascular complications of chronic kidney disease (CKD). CKD is a significant public health problem worldwide with a global prevalence of 11% to 13% and can lead to a high prevalence of morbidity and mortality. The pathophysiology and DM and CKD include inflammation, oxidative stress and apoptosis. Agents that inhibit inflammation and increase antioxidative capacity may be considered as adjunctive therapy for patients with DM and CKD. Flaxseed, melatonin, gum acacia and betaine all have been shown to possess strong antioxidant and anti-inflammatory properties. They have been found to be useful agents in animals with induced CKD. The effect of treatment with different combinations of these agents will be investigated in diabetic rats with adenine ? induced CKD, using several conventional and novel physiological, biochemical, histopathological, immunohistochemical and molecular parameters. Diabetes will be induced in rats by injection of nicotinamide ? streptozotocin and adenine (0.25% w/w, 4 weeks) will be used to induce CKD. This is a valid and reliable animal model of human CKD. These rats will then be randomly divided to receive different combination of flaxseed, melatonin, gum acacia and betaine. The physiological measurements will include changes in body and kidneys weight, blood pressure, as well as feed and water intake and fecal and urine output. The biochemical measurements in plasma, urine and renal homogenates will include conventional indices (e.g., urea, creatinine, creatinine clearance) and newer indices (e.g. NGAL, NAG, KIM, Cystatin C, and several oxidative and nitrosative, inflammatory, and anti-inflammatory indices). Several proteins and biomarkers (e.g. NF ?B, Nrf2 signaling pathways) will be studied by immunohistochemistry and Western blotting techniques.