THE VALUES AND THE DIFFERENCES OF THE SEROTONIN LEVELS IN SERUM AND BRAIN TISSUE IN AN INDUCED DIABETIC NEPHROPATHY WHITE LABORATORY RAT UNDER THE IMPACT OF PERINDOPRIL AND CANDESARTAN

Abstract

Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-aldosterone system (RAAS) and plays a role in the pathophysiology of hypertension, heart failure, renal failure and other cardiovascular disorders. RAAS is activated in diabetic nephropathy (DN) and leads to more renal damage. Angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers suppress this (ARBs). A large body of evidence demonstrates that, in addition to its typical activity as a hormone, Ang II is a neuropeptide produced by the central nervous system (CNS) that acts as a regulator of neurotransmission and nerve cell excitability. Peripheral serotonin is an endocrine component that promotes energy storage efficiency. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue. However, the actions of serotonin extend beyond neuronal communication in the CNS and enteric nervous system (ENS) to peripheral tissues. Serotonin mediates numerous nonneuronal processes such as bladder function, respiratory drive, hemostasis, vascular tone, immune function, and intestinal inflammation . The goal of this study is to see how the ACE inhibitor perindopril and the ARB AT1 candesartan, taken singly and in combination (double blockade), affect serotonin levels in the serum and brain tissue of Wistar rats with DN caused by streptozotocin (STZ). The levels of serotonin in the serum and brain of four experimental groups of animals were measured using an enzyme-linked immunosorbent assay (ELISA): a control group with DN, a group with DN treated with perindopril, a group with DN treated with candesartan, and a DN group treated with a combination of perindopril and candesartan. Perindopril (6 mg/Kg/day), candesartan (5 mg/Kg/day), and dual therapy with perindopril (3 mg/Kg/day) and candesartan (2,5 mg/Kg/day) were given orally every day for eight weeks, beginning four weeks after STZ was given, whereas the control group received just water. The rats were slaughtered at the end of the therapy so that the serum and brain tissue could be used to test serotonin levels. The results showed that blocking the renin-angiotensin system (RAS) with perindopril, candesartan, or their combination considerably decreased serotonin levels in the serum but dramatically elevated serotonin levels in the brain tissue in all groups.