Morphogenesis of Postmortem Hepatocyte Vacuolation and Liver Weight Increases in Sprague-Dawley Rats

Abstract

Accurate interpretation of microscopic changes in tissues is critical in hazard identification and risk assessment. To address a possible confounder, the effects of postmortem interval on hepatocyte vacuolation and liver weight were studied in fasted and nonfasted Sprague-Dawley rats. Male and female rats (5/sex/interval) were euthanized with CO2, weighed, and necropsied either immediately or after remaining in the closed CO2 chamber for 5, 10, or 25 minutes after respirations ceased. The liver was removed, weighed, and fixed for light microscopy, immunohistochemistry, and electron microscopy. The liver weight and liver to body weight ratio increased significantly in both male and female rats. Postmortem hepatocellular vacuolation was more prominent in males than in females. Both fasted and nonfasted males were similarly affected, however, fasted females were affected more than nonfasted females at the 25-minute interval. Ultrastructurally, intracytoplasmic vacuoles in hepatocytes and/or endothelial cells contained electron-lucent material that was morphologically similar to plasma in sinusoidal spaces. Results of our study suggest that hepatocyte vacuoles were formed in a postmortem time-dependent manner as a result of plasma influx into the cytoplasm. This change was associated with hepatic sinusoidal congestion and increases in liver weight. Males were more sensitive than females to postmortem hepatocyte vacuolation.

Keywords

Hepatocyte vacuolation liver weight postmortem artifact rat fasted nonfasted.

References

Chandra AMS , Campbell AG , Reddy G. , Qualls CW (1999). Neurotoxicity of 1,35-trinitrobenzene (TNB): immunohistochemical study of cerebrovascular permeability. Vet Pathol 36: 212—220.

Farnell D. (1991). Centrilobular vacuolation of livers in normal rats and mice: etiologic considerations. Toxicol Pathol 19: 623.

Gottardi CJ , Gumbiner BM (2001). Adhesion signaling: how beta-catenin interacts with its partners. Curr Biol 11: R792—794.

Heid HW , Moll R. , Schwetlick I. , Rackwitz H. , Keenan TW (1998). Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tiss Res 294: 309—321.

Kasischke K. , Huber R. , Li H. , Timmler M. , Riepe MW (1999). Primary hypoxic tolerance and chemical preconditioning during estrus cycle in mice. Stroke 30: 1256—1262.

Kimura M. , Abe M. (1994). Histology of postmortem changes in rat livers to ascertain hour of death. Intl J Tiss React 16: 139—150.

LeBouton AV , Masse JP (1980). A random arrangement of albumin-containing hepatocytes seen with histo-immunologic methods. II. Conditions that produce the artifact . Anat Rec 197: 195—201.

Micozzi MS (1986). Experimental study of postmortem changes under field conditions: effects of freezing, thawing, and mechanical trauma. J Forensic Sci 31: 953—961.

Nunley WC , Dickie MW , Schuit KE (1973). Delayed, in vivo hepatic postmortem autolysis. II. Morphological changes in reticulo-endothelial cells. Virch Arch B Cell Pathol 14: 285—291.

10.

Nunley WC , Schuit KE , Dickie MW , Kinlaw JB (1972). Delayed, in vivo hepatic post-mortem autolysis . Virch Archiv B Cell Pathol 11: 289—302.

11.

Shimizu M. , Hayashi T. , Saitoh Y. , Ohta K. , Itoh H. ( 1990). Postmortem autolysis in the pancreas: multivariate statistical study. The influence of clinicopathological conditions. Pancreas 5: 91—94.

12.

Splitter GA , McGavin MD (1974). Sequence and rate of postmortem autolysis in guinea pig liver. Amer J Vet Res 35: 1591—1596.

13.

Stupfel M. , Pesce VH , Gourlet V. , Bouley G. , Elabed A. , Lemercerre C. (1984). Sex-related factors in acute hypoxia survival in one strain of mice. Aviat Space Environ Med 55: 136—140.

14.

Sykes BI , Penny E. , Purchase FH (1976). Hepatocyte vacuolation and increased liver weight occurring in anoxic rat. Toxicol Appl Pharmacol 36: 31—39.

15.

Trowell OA (1946). The experimental production of watery vacuolation of the liver. J Physiol 105: 268—297.