Naringin attenuates melamine-induced renal biochemical alterations in rats: Histopathological and immunohistochemical assessment

Naringin has shown nephroprotective activity in several toxicant models. This study evaluated renal outcomes during concurrent naringin administration and repeated melamine exposure.

Thirty Sprague-Dawley rats were allocated to five groups, each containing three males and three females: control, naringin alone (100 mg/kg/day), melamine alone (300 mg/kg/day), and melamine plus naringin (50 or 100 mg/kg/day). Treatment continued orally for 28 days. We assessed serum creatinine, urea, and uric acid; renal superoxide dismutase activity; tumor necrosis factor-α concentrations; histopathology; and 15A3 immunoreactivity. Factorial models used individual SOD values and rounded group means, standard deviations, and sample sizes for the other biochemical outcomes to estimate treatment contrasts averaged equally across sexes. Tissue-score frequencies were summarized descriptively.

Treatment-group effects were significant for all five biochemical outcomes (all p < 0.001). Compared with melamine alone, the 100 mg/kg naringin regimen was associated with a sex-balanced mean creatinine difference of -0.640 mg/dL (Tukey-adjusted 95% CI -0.809 to -0.471). Both naringin regimens showed partial attenuation of the measured biochemical abnormalities, with larger differences at 100 mg/kg. These contrasts remained significant in a heteroscedastic sensitivity analysis. Renal SOD activity was higher than with melamine alone but remained below control values. Selected within-sex pairwise comparisons of H&E injury scores and 15A3 staining categories among the melamine-only and two co-treatment groups were not significant after Holm adjustment (all adjusted p ≥ 0.300). Separate weekly treatment-group comparisons of body weight were not significant.

Concurrent naringin administration was associated with partial attenuation of the measured biochemical abnormalities during melamine exposure. The selected pairwise analyses did not establish differences in H&E injury or 15A3 staining categories among the melamine-only and co-treatment groups. These findings do not establish recovery of renal filtration or tubular function. Small samples, summary-data inference, and antibody specificity limit conclusions about sex differences and DNA-specific injury.