Sarpogrelate, a serotonin receptor (5HT_{2 ar} ) antagonist, ameliorates renal damage in experimental mesangial proliferative glomerulonephritis

Abstract

Background. Because platelets (PLTs) and mesangial cells (MCs) express serotonin receptors (5HT_{2 ar} ), 5HT_{2 ar} blockade may ameliorate glomerulonephritis, in which these cells increase.

Methods. Anti-Thy 1.1 nephritis (ATN) was induced in 16 rats (8 animals per group) by two injections of anti-Thy 1.1 monoclonal antibody, given 2 weeks apart. Group S ingested sarpogrelate (S), a 5HT_{2 ar} antagonist dissolved in tragacanth (T) daily throughout the experimental period, whereas group T was given only the vehicle (T). Group C rats received injections of saline instead of the antibody. Rats were killed 2 and 13 weeks after the first injection (at 3 h and 11 weeks, respectively, after the second injection,). Urinary albumin (Alb)/24 h was measured by an immunodiffusion method. Urinary hydroxyindole acetic acid (U5HIAA)/24 h was measured on days 0, 7, and 14. The point-counting method was used to calculate the mesangial matrix index (MMI) and tubulointerstitial index (TII) on renal sections stained by conventional methods. Immunohistochemistry, aiming at labelling monocytes/macrophages (Mf), PLTs, and activated platelets (APLTs) by staining with ED₁, β₃-integrin, and p-selectin, respectively, was also performed.

Results. Alb/24 h was decreased in group S vs group T during the experimental period. U5HIAA/24 h was decreased in group S vs group T on day 14. At week 13, MMI and TII in group T were greater than in group S and group C, being similar in the latter two groups. Similar results were obtained in terms of ED₁, β₃-integrin, and p-selectin expression.

Conclusions. Decrease of renal injury (MMI,TII, and Mf infiltration) in association with decreased U5HIAA/24 h and p-selectin expression, indicated the suppressive role of S in the activation of 5HT_{2 ar} -bearing cells (PLT/MC), which links to amelioration of ATN.