Necrosis of the pars recta (S3 segment) of the rat kidney produced by hexachloro 1:3 butadiene

Abstract

Administration of hexachloro 1:3 butadiene (HCBD) intraperitoneally at a dose of 200 mg/kg body weight caused necrosis of the parts recta of the proximal tubules situated in the outer stripe of the outer medulla of the rat kidney. The earliest morphological changes detectable by light microscopy were observed after eight hours, with several proximal tubules showing necrosis. By sixteen hours a distinct band of tubular necrosis was seen in the outer stripe of the outer medulla. One and two days after dosing proximal tubular necrosis was still evident whereas distal tubules were unaffected. By three days, vacuolation was observed in the pars convoluta of some proximal tubules. Active tubular regeneration was apparent by day five, which was accompanied by a marked increase in renal water and nonprotein sulphydryl content (NP-SH). By day fourteen substantial recovery had occurred. Ultrastructural changes were seen as early as one hour after HCBD (300 mg/kg, ip) although necrosis was not marked until 8 hr. Mitochondrial swelling was seen 1-4 hr after dosing in the S1 and S2 segments of the proximal tubule. By 8 hr the major pathological changes were largely confined to the S2 segment and consisted of loss of brush border, mitochondrial swelling and cellular necrosis. In conclusion HCBD produces a site-specific nephrotoxic effect on the proximal tubule in the rat. The pattern of injury was similar to that associated with some other nephrotoxic and ischaemic models of acute renal failure.