Hydropic change in rat liver induced by hexachloro-1:3-butadiene

The effect of a single i.p. dose of 200 or 300 mg kg-1 hexachloro-1:3-butadiene (HCBD) on liver morphology, water, sodium and potassium ion content, cation movement and non-protein sulphydryl (NP-SH) content has been studied in rats. There was a rapid, dose-related increase in liver water which reached a maximum between 16 and 24 h after HCBD administration and then returned to control values by day 4. Associated with the increased water, there was an increase in the Na+ and K+ ions when related to the dry weight of the liver. However, the actual concentration of both cations in total liver water did not alter. The total liver DNA, protein or cytochrome P-450 concentration did not change, at a time when there was a maximal increase in liver water. There was a rapid decrease in liver NP-SH, which reached a nadir (50% of control) 8 h after HCBD administration, then increased to 150% of normal on day 5 and returned to normal by day 10. On histopathological examination, the liver appeared essentially normal, apart from a slight fatty change. Ultrastructural changes were, however, observed 8 h after dosing, when periportal hepatocytes contained occasional swollen mitochondria, whereas centrilobular hepatocytes appeared normal. By 16-24 h, mitochondrial swelling was marked in most periportal hepatocytes and some alteration in smooth endoplasmic reticulum was seen. It is suggested that HCBD or a metabolite causes disruption of mitochondria and this results in an influx of water into the cells. Normal concentrations of Na+ and K+ are, however, maintained by an intact Na+ pump.