Anti-cancer and cardioprotective effects of indol-3-carbinol in doxorubicin-treated mice.

Doxorubicin (DOX) is a broad-spectrum antitumor antibiotic used in treatment of cancer. Its effect may be complicated by increased risk of cardiotoxicity. It was suggested that natural compounds with anticancer properties can be used in combination with DOX to decrease its dose and side effects. Indole-3-carbinol (I3C) is one of the phytochemicals that was shown to have anti-cancer effect. Our aim was to detect the possible chemosensitizing effects of I3C in DOX-induced cytotoxicity and the possible cardioprotective effects of I3C in DOX-induced cardiotoxicity. One hundred mice were divided into five equal groups: Control untreated group, solid Ehrlich carcinoma (SEC), SEC + DOX, SEC + I3C, SEC + DOX + I3C. Tumor volume, serum creatinine kinase and lactate dehydrogenase were measured. Also, tissue malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), sphingosine kinase-1 (SphK1) activity and interleukin-6 (IL-6) were determined. Parts of the tumor and cardiac tissues were subjected to histopathological examination. DOX or I3C alone or in combination induced significant increase in tumor CAT and SOD with significant decrease in tumor volume, tumor MDA, SphK1 activity and IL-6 and alleviated the histopathological changes with significant increase in the apoptotic index and significant decrease in tissue bcl2 compared to SEC group. Also, DOX induced cardiotoxicity which was ameliorated by I3C. In conclusion, DOX/I3C combination had a better effect than each of DOX or I3C alone against SEC in mice with marked improvement of the cardiotoxicity induced by DOX.

Effect of atorvastatin and methotrexate on solid Ehrlich tumor.

Hydroxymethyl glutaryl CoA reductase is the key enzyme in cholesterol synthesis. A relationship was found between cholesterol and the development of many types of cancer. Atorvastatin is a hypolipidemic drug that may have a role in treatment of cancer. Moreover, atorvastatin was reported to decrease the resistance of cancer cells to many chemotherapeutic agents. The aim of this work was to study the effect of each of methotrexate (MTX) and atorvastatin alone and in combination on solid Ehrlich carcinoma (SEC) in mice. Fifty BALB/c mice were divided into five equal groups: control untreated group, SEC, SEC+MTX, SEC+atorvastatin, SEC+MTX+atorvastatin. Tumor volume, tissue glutathione reductase (GR), catalase, malondialdehyde (MDA), cholesterol and tumor necrosis factor alpha (TNF-α) were determined. A part of the tumor was examined for histopathological and immunohistochemical study. MTX or atorvastatin alone or in combination induced significant increase in tissue catalase and GR with significant decrease in tumor volume, tissue MDA, cholesterol and TNF-α and alleviated the histopathological changes with significant increase in p53 expression and apoptotic index compared to SEC group. In conclusion, the combination of MTX and atorvastatin had a better effect than each of MTX or atorvastatin alone against solid Ehrlich tumor in mice.

Comparative study between the effect of methotrexate and valproic acid on solid Ehrlich tumour.

BACKGROUND: SEC is an undifferentiated tumour used in tumour studies. MTX is an antimetabolite used in treatment of cancer, autoimmune diseases and induction of abortion. VPA is used as anticonvulsant and is under investigation for treatment of cancer. The aim of this work was to compare between the effect of each of MTX and VPA on solid Ehrlich tumour in mice. METHODS: Forty albino mice were divided into 4 equal groups: control untreated group, SEC group, SEC+MTX group, and SEC+VPA group. Tumour volume, tissue CAT, tissue GR, tissue MDA, tissue cholesterol and tissue TNF-α were determined. A part of the tumour was examined for histopathological and immunohistochemical study. RESULTS: MTX alone or VPA alone induced a significant increase in tissue CAT and GR with a significant decrease in the tumour volume, tissue MDA, cholesterol and TNF-α and alleviated the histopathological changes with a significant increase in p53 expression compared to SEC group. This effect was more significant in MTX treated group compared to VPA treated group. CONCLUSION: MTX has more antitumour effect than VPA against SEC.

Oral Nigella sativa oil ameliorates ovalbumin-induced bronchial asthma in mice.

Nigella sativa oil (NSO) is used in folk medicine as a therapy for many diseases including bronchial asthma. We investigated the possible modulating effects of NSO on asthma-like phenotypes in a mouse model of bronchial asthma. BALB/c mice were actively sensitized by intraperitoneal injections of 50 µg ovalbumin (OVA) with 1mg alum on days 0 and 12. Starting on day 22, they were exposed to OVA (1% (w/v), in sterile physiological saline) for 30 min, three times every 4th day. Negative control animals were exposed to saline in a similar manner. NSO was administered orally for 31 day from day 0 to day 30. On the day of sensitization and challenge, NSO was given 30 min before the treatment. Airway function, number of inflammatory cells in bronchoalveolar lavage fluid (BALF), levels of interleukin (IL)-4, IL-5, IL-13 and interferon (IFN)-γ in BALF, serum levels of total IgE, OVA-specific IgE, IgG1 and IgG2a, and histopathological examination of lung tissues were investigated. Oral treatment with NSO showed significant decrease in airway hyperresponsiveness, the number of total leukocytes, macrophages and eosinophils, levels of IL-4, IL-5 and IL-13 in BALF, serum levels of total IgE, OVA-specific IgE and IgG1, and significant increase in BALF level of IFN-γ and serum level of OVA-specific IgG2a, indicating restoration of local Th1/Th2 balance. Furthermore, it significantly abrogated the histopathological changes of the lungs, as the images were nearly normal. These results suggest that the treatment with oral NSO could be a promising treatment for bronchial asthma in humans.

Study of Atorvastatin in experimental allergic airway inflammation in mice.

BACKGROUND: Inflammation and oxidative stress are associated with airway diseases. There is growing evidence that Atorvastatin could be used as a therapy for these conditions. OBJECTIVE: On these bases, we evaluated Atorvastatin as a protective and reversal treatment for the allergic airway diseases in mice model. We also looked at the possible interaction with the currently used effective medication. METHODS: Mice were sensitized and challenged with ovalbumin (OVA) to develop features of allergic airway diseases mainly of bronchial inflammation. Atorvastatin was injected during or after the sensitization and challenge process to evaluate its protective or reversal effects, respectively. Total and differential cells in the BAL fluids together with IL-4, IL-5 and IL-10 cytokine levels were evaluated. Total IgE and cholesterol levels in serum were studied. RESULTS: In the protective phase, Atorvastatin inhibited the OVA-induced cellular infiltration of lung bronchi, decreased IL-4 and IL-5 and prevented the increase in IL-10 cytokine levels. Also, it reduced the OVA-induced high serum total IgE level. Injection of Atorvastatin after challenge was not effective in reversing the inflammatory process, with no major contribution towards augmenting the actions of Dexamethasone. The cholesterol lowering effect was marked in the protective phase while less effective for the reversal phase. CONCLUSION: Our results indicate that Atorvastatin reduced the allergic inflammatory features in mice and it could be useful towards developing a better therapeutic regimen for the treatment of allergic diseases.