Potential anti-fibrotic effect of deferoxamine in concanavalin A-induced liver fibrosis.
Samar Fathy Moustafa Darwish;
Abstract
The current work was designed to elucidate the possible anti-fibrotic effect of DFO in rat model of immunological liver fibrosis, which resembles the pathological changes in autoimmune and viral hepatitis in human, and to investigate the additional usefulness of DFO to peg IFN-α-based therapy and the possible underlying mechanisms. To fulfill these goals, this study was divided into two parts:
Part I: Screening the hepatoprotective dose of DFO against Con A-induced acute hepatotoxicity:
Thirty six male albino rats were divided into six groups(n=6). Group 1 was control rats and injected only with normal saline, group 2 received single dose of Con A dissolved in saline (20 mg/kg, i.v.) andgroups (3, 4, 5 and 6) were injected with different doses of DFO dissolved in saline (75, 150, 300, 600 mg/kg, i.p., respectively), then after 1 h they were injected by Con A.After 24 h from Con A injection, serum samples were collected from each group,then the animals were sacrificed and liver tissues were isolated.
Studied parameters in part I:
a) Assessment of Liver enzymes: ALT & AST
b) Histopathological examination of liver using H&E stain.
The present results revealed that, single injection of Con A induced acute hepatotoxicity, through the significant increase in liver enzymes, associated with degenerative changes andinflammatory infiltration upon histopathological examination. Screening different doses of DFO showed that, pre-treatment with 300 mg/kg of DFO represented the most hepatoprotective dose, evidenced by the significant improvement in liver enzymes levels, and preserving the normal architecture of hepatocytes.
Part II: Studying the potential anti-fibrotic mechanisms of DFO in chronic immunological model of liver fibrosis:
The chosen dose of the DFO(300mg/kg) in the previous stepwas tested for the possible anti-fibrotic effect using immunologic model of liver fibrosis. Seventy rats were randomized into 7 groups (n=10) and treated for 6 weeks. Group 1: control group and received only saline. Groups 2 or 3 received only DFO (300 mg/kg, 3times/week, i.p.) or peg IFN-α (1.5 µg/kg/week, s.c.), respectively. Group 4 was injected with Con A (15mg/kg/week, i.v.) to induce liver fibrosis. Groups 5, 6 or 7 received Con A together with DFO, peg IFN-α or both, respectively. At the end of the experiment, serum samples were collected from each group,then the animals were sacrificed and liver tissues were isolated.
Studied parameters in part II:
a) Assessment of hepatotoxicity indices:
1- Body weight & Liver index
2- Liver enzymes: ALT & AST
3- Total cholesterol
4- Triglycerides
5-Albumin
6- Total bilirubin
b) Histopathological examination of liver using H&E stain.
c) Assessment of oxidative stress markers:
1- TAC of liver
2- Liver content of GSH
3- Liver content of lipid peroxides as MDA
4- SOD activity in liver
Part I: Screening the hepatoprotective dose of DFO against Con A-induced acute hepatotoxicity:
Thirty six male albino rats were divided into six groups(n=6). Group 1 was control rats and injected only with normal saline, group 2 received single dose of Con A dissolved in saline (20 mg/kg, i.v.) andgroups (3, 4, 5 and 6) were injected with different doses of DFO dissolved in saline (75, 150, 300, 600 mg/kg, i.p., respectively), then after 1 h they were injected by Con A.After 24 h from Con A injection, serum samples were collected from each group,then the animals were sacrificed and liver tissues were isolated.
Studied parameters in part I:
a) Assessment of Liver enzymes: ALT & AST
b) Histopathological examination of liver using H&E stain.
The present results revealed that, single injection of Con A induced acute hepatotoxicity, through the significant increase in liver enzymes, associated with degenerative changes andinflammatory infiltration upon histopathological examination. Screening different doses of DFO showed that, pre-treatment with 300 mg/kg of DFO represented the most hepatoprotective dose, evidenced by the significant improvement in liver enzymes levels, and preserving the normal architecture of hepatocytes.
Part II: Studying the potential anti-fibrotic mechanisms of DFO in chronic immunological model of liver fibrosis:
The chosen dose of the DFO(300mg/kg) in the previous stepwas tested for the possible anti-fibrotic effect using immunologic model of liver fibrosis. Seventy rats were randomized into 7 groups (n=10) and treated for 6 weeks. Group 1: control group and received only saline. Groups 2 or 3 received only DFO (300 mg/kg, 3times/week, i.p.) or peg IFN-α (1.5 µg/kg/week, s.c.), respectively. Group 4 was injected with Con A (15mg/kg/week, i.v.) to induce liver fibrosis. Groups 5, 6 or 7 received Con A together with DFO, peg IFN-α or both, respectively. At the end of the experiment, serum samples were collected from each group,then the animals were sacrificed and liver tissues were isolated.
Studied parameters in part II:
a) Assessment of hepatotoxicity indices:
1- Body weight & Liver index
2- Liver enzymes: ALT & AST
3- Total cholesterol
4- Triglycerides
5-Albumin
6- Total bilirubin
b) Histopathological examination of liver using H&E stain.
c) Assessment of oxidative stress markers:
1- TAC of liver
2- Liver content of GSH
3- Liver content of lipid peroxides as MDA
4- SOD activity in liver
Other data
| Title | Potential anti-fibrotic effect of deferoxamine in concanavalin A-induced liver fibrosis. | Other Titles | إحتمالية تأثير الديفيروكسامين كمضاد للتليف في تليف الكبد المحدث بالكونكانافالين أ | Authors | Samar Fathy Moustafa Darwish | Issue Date | 2015 |
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