Effects of pirfenidone on an acute phase of anti-Thy-1 nephritis

Abstract

Background. 5-Methyl-1-phenyl-2-(1H)-pyridone (pirfenidone [PD]) has anti-fibrotic and anti-inflammatory effects. Previous reports have indicated that PD can prevent the progression of chronic kidney fibrosis in some animal models. It has not yet been reported, however, whether PD is capable of controlling acute inflammation of the kidney.

Methods. The present study was designed to observe the effect of PD on an acute phase of anti-Thy-1 nephritis, a well known model for acute kidney inflammation. Male standard Wistar rats (specific pathogen-free [SPF] level), 7 weeks old (day −10, 141.52 ± 2.60 g) were divided into two groups. In group C (n = 7), 0.7 ml of anti-Thy-1 antibody was injected intravenously on day 0. In group P (n = 6), anti-Thy-1 antibody was injected similarly, and PD (500 mg/kg BW per day) was given daily by dietary intake starting 1 day before the first injection and continuing throughout the study. All rats were killed on day 7 and subjected to light microscopic and serum biochemical examinations. The degree of glomerular extracellular matrix (ECM) expansion was determined as a matrix score, using a semiquantitative method. Differences between the two group scores were analyzed by a non-parametric test.

Results. The mean matrix score for group C was 87.6 ± 11.8, against 71.5 ± 12.5 (P < 0.05) for group P. The mean cell count for the 140 glomeruli in group C was 75.3 ± 6.1, and for the 120 glomeruli in group P it was 78.2 ± 11.6 (no significant difference). However, the possibility could not be ruled out that the degree of initial mesangiolysis in group P had been smaller than that in group C. Serum creatinine and blood urea nitrogen (BUN) levels were within the normal range in both groups.

Conclusions. It is possible that PD is capable of partially controlling acute phases of anti-Thy-1 nephritis. More detailed studies in the future will establish the validity of the short-term effects of PD on this animal model.