Quantitative Analysis of Intralobular Distribution of Microcystin-LR in the Mouse Liver.

Abstract

We described the use of image analysis for determination of the intralobular distribution of microcystin-LR (L, L-leucine and R, L-arginine) and compared the results with liver injuries. Gray level was measured in each intralobular region and converted to optical density by using the equation, which was established by employing Kodak gray scales; the immunointensity was calculated by subtracting optical density in control animals from optical density in treated animals. When mice received a single injection of 0, 40.0, 48.0 or 57.6 μg/kg and were killed at 24 hours after treatment, immunointensity was increased in a dose-dependent manner. Microcystin-LR was localized most abundantly in the centrilobular region, moderately in the midlobular region, and slightly in the perilobular region. Higher frequency of apoptosis was only found in the centrilobular region at 57.6 and 48.0 μg/kg and in the midlobular region at 57.6 μg/kg. When mice received a single injection of 60.0 μg/kg and were killed at several time points within 24 hours, immunointensity showed a similar central-to-portal gradient in the hepatic lobule, attained the highest level at 11 hours, and then gradually decreased in a time-related manner. Microcystin-LR caused hemorrhage within 7 hours, followed by paracentral necrosis and apoptosis that were observed mostly in the centrilobular and midlobular regions. The results suggest that liver injuries might occur in association with the intensity and distribution of microcystin-LR.