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

Marwan T. M. Abofila, Azab Elsayed Azab, Asma Nagib Ali, Adel Salah El Din Zohdy, Ghada Farouk Mohammed, Azza Abdel Monaem Attia

Universal Journal of Gastroenterology and Hepatology 1(1); 10.31586/ujgh.2022.509 - November 04, 2022

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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.

Figure 1. Photomicrographs of sections of the livers of animals of subgroup IA showing the normal control structure of the liver. CV = central vein, P.A. Portal area. Notice the minimal collagenous fibres content in the stroma, especially in portal areas. (P.A) [figure D]. Also moderate content of PAS +ve glycogen granules is appeared in the hepatocytic cytoplasm [figure B]. A - H&E 40, B - H&E 200, C - PAS 400, D - Masson tricome 100.

Figure 2. Photomicrographs of sections of the livers of animals of subgroup IB showing the ballooned hepatocytes with their severely vacuolated cytoplasm (A) which is intensely packed with PAS +ve glycogen granules (B). a - H&E 400, b - PAS 400

Figure 3. A photomicrograph of section of the liver of an animal of subgroup IIA showing the increased ballooning and vacuolation of hepatocytes at the periphery of the hepatic lobules (zone I&II). H&E 200

Figure 4. A photomicrograph of section of the liver of an animal of subgroup IIA showing the hepatocytes of the periphery of the hepatic lobules more depleted and vacuolated with well circumscribed vacuoles compared to the central zone. PAS 200

Figure 5. A photomicrograph of section of the liver of an animal of subgroup IIA showing the minimal content of collagenous fibers stroma. Masson trichome 100

Figure 6. A photomicrograph of section of the liver of an animal of subgroup IIB showing the dilated blood sinusoids and the vacuolated hepatocytes all over the lobules. H&E 200.

Figure 7. A photomicrograph of a section of the liver of an animal of subgroup IIB showing that the hepatocytes are relatively depleted from the PAS +ve granules content and vacuolated with well circumscribed vacuoles. PAS 400

Figure 8. A photomicrograph of section of the liver of an animal of subgroup IIB showing the minimal content of collagenous fibres stroma. Notice a focal area of necrosis (*). Masson trichome 100

Figure 9. Two photomicrographs of sections of the livers of animals of subgroup IIC showing marked ballooning of the hepatocytes and vaculation of their cytoplasm with well circumscribed vacuoles as well depletion of the cytoplasmic PAS +ve glycogen granules specially in the periphery of the hepatic lobules. A – H&E 200, B – PAS 400.

Figure 10. A photomicrograph of a section of the liver of an animal of subgroup IIC showing mild increase in the collagen fibers content in the stroma compared to the control specially in the portal area. Masson trichome 100

Figure 11. Photomicrographs of sections of the livers of animals of subgroup IIIA showing that the hepatocytes in a wide area of the periphery of the hepatic lobules are ballooned and has deeply stained eccentric nuclei. The cytoplasm is occupied by well circumscribed vacuoles and depleted from its PAS +ve glycogen granules. A: H&E 100, B: H&E 200, C: PAS 400

Figure 12. A photomicrograph of a section in the liver of an animal of subgroup IIIA showing the minimal collagen fibers content in the stroma comparable with the control group. Masson tricome 100

Figure 13. Two photomicrographs of sections of the livers of animals of subgroup IIIB showing the extension of the hepatocytic ballooning, vacuolation and depletion of PAS +ve granules all over the lobules. a - Masson trichome 100, b - PAS 400

Figure 14. Two photomicrographs of sections of the livers of animals of subgroup IIIC showing the severe affection of the hepatocytes all over the hepatic lobules. The cells appear severely ballooned, vacuolated and completely depleted from their PAS +ve granules. A relative increase in collagenous fibrosis of the stroma is appearent. a- Masson trichome 100, b- PAS 100

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