Pathological and immunohistochemical changes in the liver of monocrotaline-treated rats

Abstract

Pathological and immunohistochemical changes in livers were investigated in monocrotaline-treated rats. Eighty adult-male Wistar rats were distributed in 5 groups, each containing 16 animals according to monocrotaline dose (Group I: 50 mg/kg, Group II: 100 mg/kg, Group III: 150 mg/kg, and Group IV: 200 mg/kg). The control group was administered with physiological saline. Half of the animals in each group were euthanized at the 18th hour while the remaining half at the 6th week postinoculation. At the end of the 18th hour, the most prominent lesion was hepatocytic apoptosis which was dose-dependent. Apoptotic cells were mostly located in periportal and mid-zonal areas. The TUNEL staining was consistent with morphological findings. Mild to moderate sinusoidal congestion, vacuolar and fatty degeneration were present in all the experimental groups. On the other hand, no difference was detected between the experimental and control groups in proliferating cell antigen nuclear (PCNA) staining, whereas Bax/Bcl-2 staining was present in all the experimental groups with a dose-dependent manner. At the end of the 6th week, hepatic megalocytosis, bile duct proliferation, postnecrotic fibrosis were the main findings. The severity of the lesions was dose-dependent, and few intranuclear inclusion bodies were also detected at the highest dose. At this period, hepatocytes were slightly stained by Bax and Bcl-2, whereas PCNA and TUNEL staining were intensive. In conclusion, monocrotaline showed different effects on the liver depending on dose and duration of the exposure, and the use of doses below 100 mg/kg may be recommended for long-term monocrotalin toxicity studies.