Experimental monocrotaline toxication in rats: Histopathologic and immunohistochemical examinations

Histopathological and immunohistochemical studies were performed in experimentally induced monocrotalin toxication in rats. Monocrotaline is a member of pyrrolozidin alkaloids (PAs) and has been widely used as a model for pyrrolizidine alkaloid toxication. Eighty adult, male Wistar rats (120-200gr.) were divided into 5 groups (16 animals in each group) in terms of intraperitoneal monocrotaline injection including 50 mg / kg (I. group), 100 mg / kg (II. group), 150 mg / kg (III. group), and 200 mg / kg (IV. group) monocrotalin. Fifth group was designed as control group and these animals were administrated single dose of intraperitoneal physilogical saline. Thirty and 50 animals were euthanized in 18 hours and 6 weeks at postinoculation, respectively. Accordingly, following results were obtained. 1. At the end of 18 hours; the most striking lesion was hepatocytic apoptosis which was present in all experimental group sand the number of apoptotic cells increased in a dose dependent manner. The most common location of these apoptotoic cells were periportal and mid-zonal areas. TUNEL staining was completely in agreement to morphologic findings. Other changes detected were mild to moderate sinusoidal congestion, vacuolar and fatty degeneration. The degenerative changes were moderate to severe and diffuse in distribution in all test groups. 2. The extra-hepatic changes including renal, pulmonary, testicular, splenic and intestinal were minimal to absent in all the experiment, groups at the end of 18 hours. 3. At the end of 18 hours; no difference was present in proliferating cell antigen nüclear (PCNA) staining among the test and control groups liveer sections. 4. In regard to; Bax/Bcl-2 staining, there was statistically difference between in highest and moderate dose goups in control group. 5. At the end of 6 th weeks; dose dependent megalohepatocytosis, bile duct proliferation, post necrotic and capsular fibrosis were the main finding detected. In highest dose group; scant intranuclear inclusion bodies were also present. 6. Biochemically; ALT and AST levels in plazma were increased in all dozed groups as comparedto control at the end of 18 hours. Whereas, GGT level was incresaed in test groups and the end of 6 weeks. In conlusion, apoptotic changes in liver reached the highest values at the end of 18 th hour post-inoculaotion with the intra peritoneal monocrotaline application in chronic cases, apoptosis was observed to decrease megalocytosis occured as a result of antimitotic effect.