Hepatic Histopathological Alterations induced by L-Arginine and/or Dexamethasone in Adult Male Albino Rats

Abstract

The liver is critical organ for metabolic homeostasis and toxic substance clearance and plays an important role in the systemic response to critical illness. Acute panreatitis (AP) progresses with a local production of inflammatory mediators, eventually leading to systemic inflammatory response syndrome. Knowing that almost all pancreatic mediators released from the pancreas to the blood stream may pass through the liver before their dilution in the systemic circulation, it would be reasonable to assume a determinant role of this organ in development of the inflammatory response associated with acute pancreatitis. Objectives: The study aimed to investigate the time courses of the effects of the exogenous glucocorticoids agonist dexamethasone on microscopical changes occurring in the liver of rats used as a model of AP induced by L-Arginine. Materials and Methods: 60 adult male albino rats weighing 150-200 gm were used. They were divided into 3 groups: Control group: Which is also divided into 2 subgroups (a & b) each of animals of the first were IM injected with 0.5ml/100gm B.W saline and those of second were injected by 0.5mg/100gm B.W dexamethasone. L-Arginine group: which received L-Arginine to induce AP. The animals of this group were divided into 3 subgroups a, b and c the animals of which were sacrificed 3 days, 2 weeks and 1 month after L-Arginine injection respectively. Dexamethasone and L-Arginine group: in which the animals were injected with both L-Arginine and dexamethasone. They were also divided into 3 subgroups a, b and c, the animals of which were sacrificed 3 days. 2 weeks, one month after the injection of the drugs. The liver of the scarified animals were dissected out and prepared for microscopical examination. Results: The histopathological changes that occurred in the livers of acute pancreatitis (AP) model animals started in the periphery of the classic hepatic lobules and progressively extended in a centripetal manner to involve all the cells of the lobules in the late period of the experiment. These changes were in the form of ballooning of the hepatocytes, progressive vacuolation of their cytoplasm most propably with fat globules and depletion of the PAS+ve glycogen granules. Injection of dexamethasone in AP model animals did not improve the case, but on the contrary it made the changes more intense, severe, and rapid. One month after injection of L-Arginine and dexamethasone, the hepatocytes all over the hepatic lobules were severely affected. They were markedly ballooned with severely vacuolated cytoplasm which was completely depleted from its PAS +ve glycogen granules, indicating severe fatty degeneration of the liver. Conclusion: From the previous data, it can be concluded that treatment of AP with dexamethasone is caused a late bad effect on the liver, where it causes its late fatty liver changes.