Examination of caspase-dependent apoptotic and necrotic changes in rat kidney exposed to different doses of permethrin

Abstract

We investigated dose-related pathological alterations and apoptosis in rat kidney tissue exposed to permethrin. Histopathological findings, apoptotic cell death and urinary 3-phenoxybenzoic acid concentrations (3-PBA) were evaluated. Different doses of permethrin were administered to animals by oro-gastric gavage. A dose-dependent increase of urine 3-PBA concentration was observed in all the permethrin-treated groups. SDS-PAGE separated 30-45 kD and 100-220 kD protein bands in all experimental groups. Histopathologically, degenerative changes were observed in the epithelial lining of the S1, S2, and S3 segments of the renal proximal tubules. Apoptotic cells were seen in the inner stripe of the outer medulla in Group I, and both the cortex and medulla in Groups II and III. Immunohistochemical staining of caspase 3 and caspase 9 also was observed in the same areas. Our results suggest that damage to regions of the proximal tubules is dose-related, and caspase-9-dependent, mitochondria-related apoptotic cell death could play an important role in permethrin-induced nephrotoxicity. We also observed morphologically necrotic cells. We concluded that both necrosis and apoptosis are produced by permethrin.