Amelioration of doxorubicin-induced myocardial oxidative stress and immunosuppression by grape seed proanthocyanidins in tumour-bearing mice

Zhang, Xiaoyu; Li, Wenguang; Wu, Yongjie; Gao, Ming-Tang

doi:10.1211/0022357056523

Cited by 64 publications

(50 citation statements)

References 42 publications

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“…Previous in vivo anticancer combinatorial study of doxorubicin showed that the combination of doxorubicin and proanthocyanidin strongly improved the anti-tumour effect of doxorubicin and immune responses, and eliminated myocardial oxidative stress on rats induced by doxorubicin (Zhang et al, 2005a). In vivo study of apigenin on in vitro and in vivo genotoxicity showed decreasing doxorubicin induced genotoxicity on in vitro model, and decreasing genotoxicity on rats induced by cyclophosphamide, possibly due to inhibition of chemotherapeutics metabolic activation (Bokulić et al, 2011).…”

Section: Discussionmentioning

confidence: 98%

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Immunomodulatory Effects of Hexane Insoluble Fraction of Ficus septica Burm. F. in Doxorubicin-treated Rats

Nugroho

Hermawan²,

Nastiti³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The use of chemotherapeutics induces cardiotoxicity and affects immune functions, therefore development of combinatorial agents against cardiotoxicity and immunosuppression needs to be explored. Previous studies of the hexane insoluble fraction (HIF) of an ethanolic extract of Ficus septica leaves showed anticancer effects singly and in combination with doxorubicin on T47D breast cancer cells. In this present study, it was evaluated for its immunomodulatory activities in doxorubicin-treated rats. Thirty male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, receiving oral saline 10 ml/kg BW (control group); Group 2, receiving HIF dose 750 mg/kg BW orally, once daily; Group 3, receiving HIF dose 1.500 mg/kg BW orally, once daily; Group 4, given oral saline 10 ml/kg BW (normal group); Group 5, receiving HIF dose 1.500 mg/kg BW orally, once daily. The rats of group 1-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1 and 4 to suppress immune functions. Concomitantly, the rats were treated with saline or HIF for seven consecutive days (1 to 7). Treatment of HIF succeeded in reducing side effects of doxorubicin based on increasing lymphocyte density and phagocytosis activity and capacity of macrophages, as well as increasing the CD8+ blood level and decreasing spleen IL-10 expression. Hexane insoluble fraction of of ethanolic extract of Ficus septica leaves has potential as a protective agent combined with doxorubicin.

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Section: Discussionmentioning

confidence: 98%

“…Reportedly, doxorubicin suppressed the production of IL-2 and INF-gamma, NK cell cytotoxicity, lymphocyte proliferation and CD4+/CD8+ ratio in tumour-bearing mice (Zhang et al, 2005a). Administration of doxorubicin on rats also increase production of pro inflammatory cytokines (Santos et al, 2010).…”

Section: Introductionmentioning

confidence: 96%

Immunomodulatory Effects of Hexane Insoluble Fraction of Ficus septica Burm. F. in Doxorubicin-treated Rats

Nugroho

Hermawan²,

Nastiti³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…The suppression of immune system will lead to patient susceptible to infections and other diseases (Patel et al, 2007). Previous study from Zhang et al (2005) showed that doxorubicin inhibits lymphocyte proliferation and decrease the number of leukocytes as the result. Doxorubicin can cause DNA damage in cells of the spinal cord (Uspenskaya et al, 2004), leading to suppression of immune cells.…”

Section: Ecd Repair Hematology Profile Against Immunosupressan Effectmentioning

confidence: 99%

“…However, the use of doxorubicin is reported to have side effects included hair loss, sore throat, even cardiotoxicity (Bustova, 2009). In addition, doxorubicin also affects the immune system by decreasing the production of interferon-γ, natural killer cells (NK), the expression of IL-2, proliferation of lymphocytes, and the ratio of CD4 + / CD8 + (Zhang et al, 2005). Therefore, cochemotherapeutic agent works synergistically with doxorubicin is needed to counteract the effects of immunosuppression of doxorubicin.…”

Section: Introductionmentioning

confidence: 99%

Elettaria cardamomum Distillate Increases Cellular Immunity in Doxorubicin Treated Rats

Raksamiharja

Zulharini

et al. 2012

Indones J Cancer Chemoprevent

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Doxorubicin is one of chemotherapeutic agent used for cancer therapy. However, doxorubicin usage causes some adverse effects, such as lymphocyte, CD4+ and CD8+ cells number. Therefore, the co-chemotherapeutic agent is required to reduce the imunosuppression effect. Cardamom (Elettaria cardamomum) contains terpenoid 1,8 cineol. This research aimed to know the effect of Elettaria cardamomum distillate (ECD) in combination with doxorubicin on Sprague Dawley rat's hematology profile and the amount of CD4+ and CD8+ cells. The experiment was done for 13 days using 6 groups of rats: I doxorubicin (dox) 15 mg/kg BW; II dox + ECD5 mg/kg BW; III dox + ECD 50 mg/kg BW; IV dox + ECD 100 mg/kg BW; V ECD 100 mg/kg BW; VI control without treatment. The hematology profile and the amount of CD4+ and CD8+ were counted before and after treatment using flowcytometer. The results show that ECD increases the amount of lymphocyte, white blood, CD4+ and CD8+ cells in dose dependent manner in doxorubicin treated rats. Based on the data, it can be concluded that ECD is potential to be developed as immunostimulant agent for chemotherapy.

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“…DOX side effects, such as cardiomyopathy, have been found to be related to the formation of free radicals after reacting with oxygen [2]. DOX can also affect the immune system by decreasing interleukin-2 (IL-2) and producing interferon-γ (INF-γ), decreasing natural killer cells, lymphocyte cells, the CD4+/CD8+ ratio, as well as damaging the thymus organ [3,4]. Because of these harmful side effects, the use of natural products as a complementary therapy for cancer treatment has been widely accepted.…”

Section: Introductionmentioning

confidence: 99%

Polysaccharide-Rich Fraction of Noni Fruit (Morinda citrifolia L.) as Doxorubicin Co-Chemotherapy: Evaluation of Catalase, Macrophages, and TCD8+ Lymphocytes

Sasmito

2015

Sci. Pharm.

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Noni fruit (Morinda citrifolia L.) has been acknowledged for its cytotoxic and immunostimulatory activity. Our previous results on the immunomodulatory effect of a noni juice polysaccharide-rich fraction encouraged this research to evaluate the potency of the polysaccharide-rich fraction as co-chemotherapy with doxorubicin (DOX) administration. Macrophage activity (MA) was evaluated with the latex bead method. The phagocytic index (PI) was measured as the number of latex beads ingested by 100 macrophages, while the phagocytosis ratio (PR) was indicated by the percentage of macrophages that ingested three or more latex beads. The CEC was evaluated by using a commercial assay kit, while CD8+ T lymphocyte proliferation was evaluated using a flowcytometry method following in vivo administration. Thirty male Wistar rats were divided into five groups (n = 6 each). The control group received DOX via i.p. at a concentration of 4.67 mg/kg BW on days 1 and 4; four treatment groups received PF p.o. at a concentration of 25; 50; 100; 200 mg/kg BW daily, respectively, and additionally DOX i.p. 4.67 mg/kg BW (days 1 and 4) for 7 days. The phagocytic activity was not affected significantly by PF administration compared to the Dox control, but PF administration at a dose of 25 and 50 mg/kg BW has been proven to increase TCD8+ cell proliferation in combination 480 E. Sasmito et al.: Sci Pharm. 2015; 83: 479-488 with DOX. The catalase concentration, on the other hand, significantly decreased following PF administration at a dose of 100 mg/kg BW. The results suggest that the polysaccharide-rich fraction of noni juice might induce immunomodulatory effects via TCD8+ activation, have antioxidant activity, and thus might be a potential candidate to be used as an adjuvant to DOX chemotherapy.

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Amelioration of doxorubicin-induced myocardial oxidative stress and immunosuppression by grape seed proanthocyanidins in tumour-bearing mice

Cited by 64 publications

References 42 publications

Immunomodulatory Effects of Hexane Insoluble Fraction of Ficus septica Burm. F. in Doxorubicin-treated Rats

Immunomodulatory Effects of Hexane Insoluble Fraction of Ficus septica Burm. F. in Doxorubicin-treated Rats

Elettaria cardamomum Distillate Increases Cellular Immunity in Doxorubicin Treated Rats

Polysaccharide-Rich Fraction of Noni Fruit (Morinda citrifolia L.) as Doxorubicin Co-Chemotherapy: Evaluation of Catalase, Macrophages, and TCD8+ Lymphocytes

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