The leukotriene B4 receptor antagonist ONO-4057 inhibits mesangioproliferative changes in anti-Thy-1 nephritis

Abstract

ONO-4057 is a specific leukotriene B4 (LTB4) receptor antagonist which inhibits human neutrophil aggregation, chemotaxis and degranulation induced by LTB4. This study was conducted to evaluate the role of LTB4 in glomerulonephritis, and to examine whether ONO-4057 moderated anti-Thy-1 nephritis. Experiment 1: Sixty Wistar rats were divided into three groups. Rats of Group A (n = 20) underwent intraperitoneal administration of placebo as a control group, rats of Group B (n = 20) first underwent intraperitoneal administration of 100 mg/kg ONO-4057 and rats of Group C (n = 20) first underwent intraperitoneal administration of 300 mg/kg ONO-4057 daily from day 3 before anti-Thy-1 antibody (OX7) injection to day 14 after OX7 injection, respectively. Experiment 2: Forty rats were divided into two groups. ONO-group (n = 20) was treated with 300 mg/kg BW of ONO-4057 and placebo-group (n = 20) with placebo daily from days 1 to 13 after OX7 injection. Urine and blood samples were collected and the kidneys were extirpated from five rats of each group sacrificed at 3 h, 24 h, day 7 or day 14 after the injection of OX7 in both experiments. Urinary protein excretion, renal function and pathological findings were analysed in each group of both experiments. (1) Glomerular infiltration by polymorphonuclear leucocytes (PMNs) and macrophages at 3 h was less in Groups B and C than in Group A, and matrix scores at day 7 were lower in Groups B and C than in Group A. Injury scores did not differ among the groups. (2) Urinary protein excretion at day 7 was less in Group C than in Group A. (3) Neither pathological findings nor urinary protein excretion differed between ONO-group and placebo-group. These results suggest that LTB4 is associated not with the pathogenesis of complement-dependent mesangial cell lysis but with that of mesangial proliferative change in anti-Thy-1 nephritis.