Amifostine Attenuates Doxorubicin-Induced Subacute Hepatic and Renal Toxicity in Rats

Figures

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  Figure 1. Influence of treatment with amifostine and/or doxorubicin on the body weight of rats during 7 days after treatment. Statistical analysis was performed using the Student t-test. The results are expressed as a percentage related to the control group on day 0. *, **—p < 0.05, 0.01 for the results in comparison with the control group. #, ##—p < 0.05, 0.01 for the results in comparison with the related DOX group. Note: all animals in each experimental group survived until day 7, when 8 animals from each group were sacrificed.

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  Figure 2. Influence of treatment with amifostine and/or doxorubicin on the body weight of rats during 8 weeks after treatment. Statistical analysis was performed using the Student t-test. The results are expressed as a percentage related to the control group on day 0. *, **, ***—p < 0.05, 0.01, 0.001 for the results compared to the control group. #, ##—p < 0.05, 0.01 for the results in comparison to the DOX6 group. Note: all animals in the DOX10-treated group died 4 weeks after treatment. All animals in the other experimental groups survived until day 56, when 8 animals from each group were sacrificed.

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  Figure 3. Influence of treatment with amifostine and/or doxorubicin on absolute (g) liver weight of rats during 8 weeks after treatment. Statistical analysis was performed using the Student t-test. *, **—p < 0.05, p < 0.01 in comparison to the control group. #—p < 0.05 for the results in comparison with the DOX6 group. Note: all animals in the DOX10-treated group died 4 weeks after treatment. All animals in the other experimental groups survived until days 7 and 56, when 8 animals from each group were sacrificed.

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  Figure 4. Influence of treatment with amifostine and/or doxorubicin on absolute (g) kidney weight of rats during 8 weeks after treatment. Statistical analysis was performed using the Student t-test. ***—p < 0.001 for DOX10 in comparison to the control group. Note: all animals in the DOX10-treated group died 4 weeks after treatment. All animals in the other experimental groups survived until days 7 and 56, when 8 animals from each group were sacrificed.

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  Figure 5. (A–D) The influence of treatment with amifostine and/or doxorubicin on white blood cells (WBC), platelets (PLT), red blood cells (RBC) and haemoglobin (HB) values during 8 weeks after treatments. Statistical analysis was performed using the Student t-test. The results are expressed as a percentage related to the baseline values on day 0. $—p < 0.05 in the comparison to the DOX6 group. &—p < 0.05 in the comparison to the DOX10 group. Note: all animals in the DOX10-treated group died 4 weeks after treatment. All animals in the other experimental groups survived until day 56, when 8 animals from each group were sacrificed.

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  Figure 6. Light micrographs of the hepatic lesions in rats on day 7 after treatment. H&E stain. Magnification 200×. (A) Normal histological structure of the hepatic tissue. (B) The AMI300-treated group is characterised only by mild cytoplasmic vacuolisation of the hepatocytes and oedema in the sinusoidal spaces. (C) In the DOX6-treated group, foci of necrotic cells are surrounded by PMNCs. (D) The DOX10-treated group is presented with complete multilobular necrosis and massive accumulation of inflammatory cells. (E) In the AMI300 + DOX6-treated group, mild vacuolar degeneration of a single hepatocyte and discrete focal PMNCs infiltrates can be observed. (F) The AMI300 + DOX10-treated group is characterised by the granularity of the cytoplasm and nuclear pleomorphism.

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  Figure 7. Light micrographs of the hepatic lesions in rats on day 56 after treatment. H&E stain. Magnification 200×. (A) Normal histological structure of the hepatic tissue. (B) The AMI300-treated group only, mild hepatic vacuolisation and oedema in the sinusoidal spaces. (C) The DOX6-treated group, necrotic hepatocytes surrounded with PMNCs and hypertrophic Kupffer’s cells. (D) The AMI300 + DOX6-treated group, vacuolarly degenerated hepatocytes with small, irregular and hyperchromatic nuclei. (E) The AMI300 + DOX10-treated group, small vacuolar degeneration of hepatocytes and nuclear pleomorphism. Note: all animals in the DOX10-treated group died 4 weeks after treatment.

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  Figure 8. Light micrographs of the renal lesions of rats on day 7 after treatment. H&E stain. Magnification 200×. (A) Normal histological structure of the renal tissue. (B) The AMI300-only-treated group had mild oedema of tubular epithelial cells. (C) The DOX6-treated group showed moderate atrophy of some glomeruli and haemorrhagic foci. (D) The DOX10-treated group showed severe degeneration and reduction of tubular epithelial cells. (E) The AMI300 + DOX6-treated group showed focal cortical and medullary cell degeneration. (F) The AMI300 + DOX10-treated group showed diffuse cortical and medullary cell degeneration surrounded by inflammatory cell infiltration and focal haemorrhages.

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  Figure 9. Light micrographs of the renal lesions of rats on day 56 after treatment. H&E stain. Magnification 200×. (A) Normal histological structure of the renal tissue. (B) The AMI300-only-treated group, with mild oedema of tubular epithelial cells. (C) The DOX6-treated group showed atrophy of some glomeruli and haemorrhagic foci surrounded by PMNCs. (D) The AMI300 + DOX6-treated group showed mild degeneration and reduction of tubular epithelial cells. (E) The AMI300 + DOX10-treated group showed marked degeneration of tubular epithelial cells surrounded by haemorrhagic foci. Note: all animals in the DOX10-treated group died 4 weeks after treatment.

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  Figure 10. Hepatic damage score—HDS (Influence of treatment with amifostine and/or doxorubicin on frequency and severity of the hepatic lesions in rats). Statistical evaluation was performed using the Kruskal–Wallis test. **, ***—p < 0.01, 0.001 vs. control (7th, 56th day), ##, ###—p < 0.01, 0.001—vs. the same treatment (7th day), &, &&&—p < 0.05, 0.001 vs. DOX6 (7th day), ++—p < 0.01 vs. AMI300 + DOX6 (7th day). Note: all animals in the DOX10-treated group died 4 weeks after treatment. All animals in the other experimental groups survived until days 7 and 56, when 8 animals from each group were sacrificed.

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  Figure 11. Renal damage score—RDS (Influence of treatment with amifostine and/or doxorubicin on frequency and severity of the renal lesions in rats). Statistical evaluation was performed using the Kruskal–Wallis test. ***—p < 0.001 vs. control (7th, 56th day), #, ##, ###—p < 0.05, 0.01, 0.001—vs. the same treatment (7th day), &, &&, &&&—p < 0.05, 0.01, 0.001 vs. DOX6 (7th day), +, +++—p < 0.05, 0.001 vs. AMI300 + DOX6 (7th day). Note: all animals in the DOX10-treated group died 4 weeks after treatment. All animals in the other experimental groups survived until days 7 and 56, when 8 animals from each group were sacrificed.