Differential Effects of Losartan and Finerenone on Diabetic Remodeling, Oxidative Stress and ACE Activity in the Gastrointestinal Tract of Streptozotocin-Induced Diabetic Rats

Gastrointestinal (GI) complications are common in diabetes, but the role of the local renin-angiotensin-aldosterone system (RAAS) in gut remodeling remains unclear. This study examined histomorphometric alterations, oxidative stress, and systemic and tissue-specific angiotensin converting enzyme (ACE) and ACE2 activity in streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats (<i>n</i> = 24) were assigned to control (CTRL), diabetic (STZ), and diabetic groups treated with losartan (STZ-LOS, 20 mg/kg/day) or finerenone (STZ-FIN, 10 mg/kg/day). After 14 days, gut samples were collected from the stomach, duodenum, jejunum, ileum, and colon for histology, glutathione measurements (GSH/GSSG), and ACE/ACE2 activity assessment. Diabetic rats exhibited increased GI wall thickness-particularly in the mucosal and muscular layers-elevated GSSG levels, and a reduced GSH/GSSG ratio. Losartan prevented these changes, whereas finerenone did not produce a significant effect. Circulating ACE and ACE2 levels were elevated, but the ACE2/ACE ratio remained unchanged. Locally, ACE activity increased across gut segments, whereas ACE2 remained stable, lowering the ACE2/ACE ratio, particularly in the duodenum and jejunum. The Z-FHL/h-HL ratio was above 1 across segments but decreased in these same regions (jejunum and duodenum). These findings highlight the protective role of losartan against diabetic GI remodeling via AT₁R blockade and suggest complex, segment-specific RAAS regulation in diabetic gut pathology.