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Selective cytoprotective effect of histamine on doxorubicin-induced hepatic and cardiac toxicity in animal models

View Article: PubMed Central - PubMed

ABSTRACT

The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5 mg/kg for rats and 1 mg/kg for mice, daily subcutaneous injection starting 24 h before treatment with Dox), Dox (2 mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox-induced cardiac and hepatic toxicity, and encourage the translation to clinical practice.

No MeSH data available.


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Histamine blocks doxorubicin-induced cytotoxic and oxidative damage in rat’s heart. (a) Heart weight determined as percentage of body weight. (b) Serum cholesterol levels. (c) Serum CK-MB levels. (d) TBARS levels expressed as nmol/mg of cardiac tissue. (e) Thiols content expressed as nmol/mg of tissue. (f) SOD activity expressed as U/mg of heart proteins. (Six to eight rats per group, *P<0.05, **P<0.01, ***P<0.001 versus control; #P<0.05, ##P<0.01 versus Dox).
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fig2: Histamine blocks doxorubicin-induced cytotoxic and oxidative damage in rat’s heart. (a) Heart weight determined as percentage of body weight. (b) Serum cholesterol levels. (c) Serum CK-MB levels. (d) TBARS levels expressed as nmol/mg of cardiac tissue. (e) Thiols content expressed as nmol/mg of tissue. (f) SOD activity expressed as U/mg of heart proteins. (Six to eight rats per group, *P<0.05, **P<0.01, ***P<0.001 versus control; #P<0.05, ##P<0.01 versus Dox).

Mentions: Dox-induced cardiotoxicity was also manifested by an increase in CK-MB and cholesterol levels and a decrease in the ratio of heart weight to body weight (Figures 2a–c). In addition, myocardial tissue from Dox-treated rats showed significant increases in TBARS production and SOD levels (Figures 2d and f).


Selective cytoprotective effect of histamine on doxorubicin-induced hepatic and cardiac toxicity in animal models
Histamine blocks doxorubicin-induced cytotoxic and oxidative damage in rat’s heart. (a) Heart weight determined as percentage of body weight. (b) Serum cholesterol levels. (c) Serum CK-MB levels. (d) TBARS levels expressed as nmol/mg of cardiac tissue. (e) Thiols content expressed as nmol/mg of tissue. (f) SOD activity expressed as U/mg of heart proteins. (Six to eight rats per group, *P<0.05, **P<0.01, ***P<0.001 versus control; #P<0.05, ##P<0.01 versus Dox).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4979467&req=5

fig2: Histamine blocks doxorubicin-induced cytotoxic and oxidative damage in rat’s heart. (a) Heart weight determined as percentage of body weight. (b) Serum cholesterol levels. (c) Serum CK-MB levels. (d) TBARS levels expressed as nmol/mg of cardiac tissue. (e) Thiols content expressed as nmol/mg of tissue. (f) SOD activity expressed as U/mg of heart proteins. (Six to eight rats per group, *P<0.05, **P<0.01, ***P<0.001 versus control; #P<0.05, ##P<0.01 versus Dox).
Mentions: Dox-induced cardiotoxicity was also manifested by an increase in CK-MB and cholesterol levels and a decrease in the ratio of heart weight to body weight (Figures 2a–c). In addition, myocardial tissue from Dox-treated rats showed significant increases in TBARS production and SOD levels (Figures 2d and f).

View Article: PubMed Central - PubMed

ABSTRACT

The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5&thinsp;mg/kg for rats and 1&thinsp;mg/kg for mice, daily subcutaneous injection starting 24&thinsp;h before treatment with Dox), Dox (2&thinsp;mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox-induced cardiac and hepatic toxicity, and encourage the translation to clinical practice.

No MeSH data available.


Related in: MedlinePlus