Effect of hesperidin on mice bearing Ehrlich solid carcinoma maintained on doxorubicin

Abstract

Doxorubicin (DOX) is widely used in cancer therapy of many carcinomas types. Unfortunately, DOX is not sufficiently effective in many cases, and increasing the dosage of it is limited due to its systemic toxicity. A citrus flavonoid hesperidin (HES) is proved to be potent antioxidant and protective agent against many diseases including cancer. In this context, the objective of this study was to examine effect of HES along with DOX on solid Ehrlich carcinoma (SEC) in mice. Forty male mice were divided into four equal groups (n = 10): control SEC, DOX, HES, and DOX + HES. HES (50 mg/kg body weight orally) was given day after day for 16 days along with DOX (4 mg/kg body weight i.p. injection) for 5 cycles every 4 days in ESC-inoculated mice. After 20 days, tumor volume, tumor weight, survival rate, tumor glutathione, nitric oxide content, and serum glutathione were determined. Tumor tissue was examined for histopathological and immunohistochemical study for p53 and VEGF. Tumor resistance for mdr1a gene was assessed in tumor tissue by RT-PCR. HES induced significant increase in tissue and serum glutathione with significant decrease in tumor volume and tumor weight. A possible role of HES to modulate gene expression of mdr1a in tumor tissue was established. In addition, HES alleviated the histopathological changes with significant decrease in p53 and VEGF expression. The use of HES as adjuvant therapy with DOX would enhance the therapeutic efficacy and alleviate the resistance to DOX in treatment of solid tumors.

Exposure to Zinc Oxide Nanoparticles Induces Neurotoxicity and Proinflammatory Response: Amelioration by Hesperidin

“…However, decrease in MDA and increase in SOD levels was observed in the HSPpretreated group. This could be attributed to the antioxidant properties of HSP against oxidative stress which is consistent with other studies that have reported protective role of HSP against oxidative stress [55][56][57][58][59]. HSP also inhibits oxidative stress and inflammation in ultraviolet B irradiation-induced skin damage in mice [60].…”

Metformin augments doxorubicin cytotoxicity in mammary carcinoma through activation of adenosine monophosphate protein kinase pathway

“…37 Furthermore, Cruet-Hennequart et al 38 reported that DOX decreased DNA content in cultured human mesenchymal stem cells and in mammary gland carcinoma. 39 The anticancer effect of MET and DOX, as observed in this study, was associated with significant increase in P53 with induction of apoptosis. Histopathological findings showed that treatment of SEC mice with various treatments increased apoptotic cell count which was significant in co-treatment group rather than mono-treatment groups.…”

“…37 Furthermore, Cruet-Hennequart et al 38 reported that DOX decreased DNA content in cultured human mesenchymal stem cells and in mammary gland carcinoma. 39…”

Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

“…Tumor volume (mm 3 ) [ 87 ] and body weight were measured every 7 days until animals were anesthetized and sacrificed. After two weeks of treatment, all mice were euthanized under anesthesia via Matrx VMS anesthesia machine (Midmark Corporation) by continuous inhalation of CO 2 , 2% isoflurane gas for 5–10 min, Tumor inhibition rate (%) was determined [ 88 ].…”