Protective effect of Octreotide on histological and ultrastructural changes in the exocrine pancreas of albino rats induced by L-asparaginase ( Elspar )

Hypothesis: this study aimed to assess the effect of Lasparaginase (ASNase) on rat pancreatic acinar cells and then investigated the preventive effects of the drug (Octreotide) one of the synthetic somatostatin analogue as a prophylactic drug against ASNase –induced pancreatic injury in rats. Material and methods: There were 7 groups of rats, control group (group1) received intraperitoneal (i.p) normal saline, experimental groups (II, IV, VI) received i.p. of ASnase at different doses 200, 500, and 1000 IU respectively for (5 days total time of experiment). The protective groups (III, V, VII) received octreotide (10μg/Kg/day) subcutaneously 8 hours before the ASNase different doses for 5 days. Results: The apparent histopathological changes observed lightly and ultrastructurally in rat pancreatic acinar cells compared to control rats were increase accumulation of apical zymogen granules of variable size and shape in acinar cells, edema, vacuolization which extend to apical portions of cells, congestion and dilatation of blood vessels and further damage in the form of focal areas of necrosis of pancreatic tissue with inflammatory infiltration of mononuclear cells mainly lymphocytes also some degree of interlobular fibrosis was detected with doses 500 and 1000 IU but minimal changes with dose 200IU. Biochemically there is significant increase of pancreatic amylase enzyme above the upper normal level in rats given 500IU ASNase group IVwhich obviously decrease after giving octreotide, no significant change in group II (ASNase 200IU),while in group VI (ASNase 1000IU) a slight non significant decrease was observed compared to control group which was slightly improved in group VII after giving octreotide. There was no significant difference between the control group and experimental groups for the serum lipase enzyme. However, Octreotide injection provided protection against histological damage manifested by disappearance of cytoplasmic vacuolation and restoration of more regular acinar pattern and the pancreatic enzymes remained within normal limits. Conclusion Although ASNase by itself did not cause pancreatitis, it did cause increased levels of pancreatic enzymes and histological damage to the pancreas associated with pancreatic injury or pre-pancreatitis in experimental animals. In this study prior treatment with octreotide prevented the development of ASNase-induced pancreatic injury, although previous clinical studies have established the usefulness of octreotide in the management of L-asparaginase induced pancreatitis and pseudocyst, they did not examine prophylactic application. [Nevine R.Taha, Hanan A.Amin and Zahraa A.ElBishi. Protective effect of Octreotide on histological and ultrastructural changes in the exocrine pancreas of albino rats induced by L-asparaginase (Elspar). Life Sci J 2013; 10(3):2609-2627]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 377