Hepatotoxicity of mitoxantrone and doxorubicin

Rutin and Quercetin Counter Doxorubicin‐Induced Liver Toxicity in Wistar Rats via Their Modulatory Effects on Inflammation, Oxidative Stress, Apoptosis, and Nrf2

“…In a DXR-induced hepatotoxicity model, similar high levels of serum indices for hepatocellular damage as well as hepatobiliary deterioration were previously reported [ 58 – 61 ]. The current data are also consistent with those previously published elsewhere [ 60 , 62 – 65 ] as elevation of the activities of ALT, AST, and ALP in the serum of rats injected with DXR has been reported. Sathesh et al [ 66 ] also stated that DXR treatment caused tissue damage as well as an increase in enzyme membrane leakage.…”

“…As demonstrated in this research, DXR enhanced the activities of the cytoplasmic enzyme ALT, the cytoplasmic [58][59][60][61]. The current data are also consistent with those previously published elsewhere [60,[62][63][64][65] as elevation of the activities of ALT, AST, and ALP in the serum of rats injected with DXR has been reported. Sathesh et al…”

Rutin and Quercetin Counter Doxorubicin‐Induced Liver Toxicity in Wistar Rats via Their Modulatory Effects on Inflammation, Oxidative Stress, Apoptosis, and Nrf2

“…In a DXR-induced hepatotoxicity model, similar high levels of serum indices for hepatocellular damage as well as hepatobiliary deterioration were previously reported [ 58 – 61 ]. The current data are also consistent with those previously published elsewhere [ 60 , 62 – 65 ] as elevation of the activities of ALT, AST, and ALP in the serum of rats injected with DXR has been reported. Sathesh et al [ 66 ] also stated that DXR treatment caused tissue damage as well as an increase in enzyme membrane leakage.…”

“…As demonstrated in this research, DXR enhanced the activities of the cytoplasmic enzyme ALT, the cytoplasmic [58][59][60][61]. The current data are also consistent with those previously published elsewhere [60,[62][63][64][65] as elevation of the activities of ALT, AST, and ALP in the serum of rats injected with DXR has been reported. Sathesh et al…”

Cumulative Mitoxantrone‐Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study

“…However, microscopic data do not support the theory that the classic late cardiotoxicity of MTX [6] may contribute to promote a secondary hepatic lesion [8] considering the absence of significant centrilobular damage or dilatation of centrilobular sinusoids by blood congestion. In another study, the hepatic histophatological results of mice treated with MTX (15 mg/kg) demonstrated intense hydropic vacuolization of the cytoplasm, necrosis areas, picnosis and nuclear lysis not recovered until 5 days after the single dose administration [9]. Accordingly, in the present study, the MTXinduced hepatic damage continued until the end of the evaluations.…”

“…The apparent contradiction between our results (increased in the GSH hepatic levels) and the previously reported data (decreases in the GSH content) may be explained by the differences in the experimental design or models. Both referred studies assessed the GSH levels 3, 4 and 5 days after MTX administration or 6 hr after high MTX concentration incubation . In the present study, significant changes in the glutathione status were seen only at the last evaluated time‐point, 28 days after the last dose administration.…”

Manganese Phosphate-Doxorubicin-Based Nanomedicines Using Mimetic Mineralization for Cancer Chemotherapy

“…It should be noted that the DOX could induce severe systematic side effects. − Apparently, the DOX-induced systematic toxicity, including cardiotoxicity and hepatotoxicity, was further detected in the DOX alone treatment group (Figure g), and it was demonstrated that the liver cell inhibition and myocardial fiber rupture could be observed in correspondence to the confirmed characteristic systematic cytotoxicity, ,,, confirmed by H&E staining of the heart and liver slices (Figure g). Moreover, no noticeable pathological changes between the MnP-DOX group and MnP group compared with the control group both in the heart and liver, as well as in the spleen, lungs, and kidney, could be identified from the H&E staining results (Figure g).…”

Rutin and Quercetin Counter Doxorubicin‐Induced Liver Toxicity in Wistar Rats via Their Modulatory Effects on Inflammation, Oxidative Stress, Apoptosis, and Nrf2

“…In a DXR-induced hepatotoxicity model, similar high levels of serum indices for hepatocellular damage as well as hepatobiliary deterioration were previously reported [ 58 – 61 ]. The current data are also consistent with those previously published elsewhere [ 60 , 62 – 65 ] as elevation of the activities of ALT, AST, and ALP in the serum of rats injected with DXR has been reported. Sathesh et al [ 66 ] also stated that DXR treatment caused tissue damage as well as an increase in enzyme membrane leakage.…”

“…As demonstrated in this research, DXR enhanced the activities of the cytoplasmic enzyme ALT, the cytoplasmic [58][59][60][61]. The current data are also consistent with those previously published elsewhere [60,[62][63][64][65] as elevation of the activities of ALT, AST, and ALP in the serum of rats injected with DXR has been reported. Sathesh et al…”

Cumulative Mitoxantrone‐Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study

“…However, microscopic data do not support the theory that the classic late cardiotoxicity of MTX [6] may contribute to promote a secondary hepatic lesion [8] considering the absence of significant centrilobular damage or dilatation of centrilobular sinusoids by blood congestion. In another study, the hepatic histophatological results of mice treated with MTX (15 mg/kg) demonstrated intense hydropic vacuolization of the cytoplasm, necrosis areas, picnosis and nuclear lysis not recovered until 5 days after the single dose administration [9]. Accordingly, in the present study, the MTXinduced hepatic damage continued until the end of the evaluations.…”

“…The apparent contradiction between our results (increased in the GSH hepatic levels) and the previously reported data (decreases in the GSH content) may be explained by the differences in the experimental design or models. Both referred studies assessed the GSH levels 3, 4 and 5 days after MTX administration or 6 hr after high MTX concentration incubation . In the present study, significant changes in the glutathione status were seen only at the last evaluated time‐point, 28 days after the last dose administration.…”

Manganese Phosphate-Doxorubicin-Based Nanomedicines Using Mimetic Mineralization for Cancer Chemotherapy

“…It should be noted that the DOX could induce severe systematic side effects. − Apparently, the DOX-induced systematic toxicity, including cardiotoxicity and hepatotoxicity, was further detected in the DOX alone treatment group (Figure g), and it was demonstrated that the liver cell inhibition and myocardial fiber rupture could be observed in correspondence to the confirmed characteristic systematic cytotoxicity, ,,, confirmed by H&E staining of the heart and liver slices (Figure g). Moreover, no noticeable pathological changes between the MnP-DOX group and MnP group compared with the control group both in the heart and liver, as well as in the spleen, lungs, and kidney, could be identified from the H&E staining results (Figure g).…”

Rutin and Quercetin Counter Doxorubicin‐Induced Liver Toxicity in Wistar Rats via Their Modulatory Effects on Inflammation, Oxidative Stress, Apoptosis, and Nrf2

“…In a DXR-induced hepatotoxicity model, similar high levels of serum indices for hepatocellular damage as well as hepatobiliary deterioration were previously reported [ 58 – 61 ]. The current data are also consistent with those previously published elsewhere [ 60 , 62 – 65 ] as elevation of the activities of ALT, AST, and ALP in the serum of rats injected with DXR has been reported. Sathesh et al [ 66 ] also stated that DXR treatment caused tissue damage as well as an increase in enzyme membrane leakage.…”

“…As demonstrated in this research, DXR enhanced the activities of the cytoplasmic enzyme ALT, the cytoplasmic [58][59][60][61]. The current data are also consistent with those previously published elsewhere [60,[62][63][64][65] as elevation of the activities of ALT, AST, and ALP in the serum of rats injected with DXR has been reported. Sathesh et al…”

Cumulative Mitoxantrone‐Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study

“…However, microscopic data do not support the theory that the classic late cardiotoxicity of MTX [6] may contribute to promote a secondary hepatic lesion [8] considering the absence of significant centrilobular damage or dilatation of centrilobular sinusoids by blood congestion. In another study, the hepatic histophatological results of mice treated with MTX (15 mg/kg) demonstrated intense hydropic vacuolization of the cytoplasm, necrosis areas, picnosis and nuclear lysis not recovered until 5 days after the single dose administration [9]. Accordingly, in the present study, the MTXinduced hepatic damage continued until the end of the evaluations.…”

“…The apparent contradiction between our results (increased in the GSH hepatic levels) and the previously reported data (decreases in the GSH content) may be explained by the differences in the experimental design or models. Both referred studies assessed the GSH levels 3, 4 and 5 days after MTX administration or 6 hr after high MTX concentration incubation . In the present study, significant changes in the glutathione status were seen only at the last evaluated time‐point, 28 days after the last dose administration.…”

Manganese Phosphate-Doxorubicin-Based Nanomedicines Using Mimetic Mineralization for Cancer Chemotherapy

“…It should be noted that the DOX could induce severe systematic side effects. − Apparently, the DOX-induced systematic toxicity, including cardiotoxicity and hepatotoxicity, was further detected in the DOX alone treatment group (Figure g), and it was demonstrated that the liver cell inhibition and myocardial fiber rupture could be observed in correspondence to the confirmed characteristic systematic cytotoxicity, ,,, confirmed by H&E staining of the heart and liver slices (Figure g). Moreover, no noticeable pathological changes between the MnP-DOX group and MnP group compared with the control group both in the heart and liver, as well as in the spleen, lungs, and kidney, could be identified from the H&E staining results (Figure g).…”