Modulation Of Phosphodiesterase Activity In Chronic Kidney Disease An Experimental Study

Abstract

Background Chronic kidney disease causes a substantial burden, affecting 10% of the global population with an annual mortality of 1.2 million. In India, the prevalence of chronic kidney disease is 17%, leading to 1.3% mortality. The current treatment strategies are based on the stages of chronic kidney disease, primarily aiming to alleviate symptoms, decelerate disease advancement, and minimize complications. The available medications are non-specific and target co-morbid conditions rather than disease. Drug repurposing, on the other side, aids in discovering novel drug targets and mechanisms of action. This may lead to enhancing the understanding of disease pathology and exploring innovative therapeutic opportunities. Objective The study aimed to explore the potential role of roflumilast in chronic kidney disease and associated co-morbid conditions. The objective is to establish a molecular mechanism of action of roflumilast in mitigating inflammatory signals and alleviating chronic kidney disease. Experimental Design The effect of roflumilast was assessed in three in-vivo models: adenine-induced chronic kidney disease (50 mg/kg adenine for 28 days, p.o.), high-fat dietstreptozotocin-induced diabetic nephropathy (high-fat diet followed by a single injection of streptozotocin 30 mg/kg, i.p.), and cisplatin-induced nephrotoxicity (single injection of cisplatin 7 mg/kg, i.p). Animals were sacrificed as per the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) guideline on the 29th day, 12th week, and 16th day, respectively. For each study, urine, blood, and tissue samples were collected to perform various biochemical parameters, including serum levels of creatinine, urea, blood urea nitrogen, uric acid, total protein, albumin, sodium, potassium, chloride, calcium, magnesium, phosphorus, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, total cholesterol, and 24- vi hour urine analysis (creatinine, urea, total protein, albumin) were performed. TGF-and#946; and fasting i