scholarly journals The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells: A Bioassay-Guided Approach

2015 ◽  
Vol 36 (3) ◽  
pp. 988-1003 ◽  
Author(s):  
Hamed Karimian ◽  
Mehran Fadaeinasab ◽  
Soheil Zorofchian Moghadamtousi ◽  
Maryam Hajrezaei ◽  
Maryam Zahedifard ◽  
...  
Keyword(s):  
Sesquiterpene Lactone ◽  
Histopathological Examination ◽  
Cancer Control ◽  
Control Group ◽  
High Dose ◽  
Mcf7 Cells ◽  
Carcinogenic Effect ◽  
Chemopreventive Effect

Background: Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE) using in in vivo and in vitro models. Methods and Results: Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels. Conclusion: This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis.

scholarly journals Antiskin Cancer and Antioxidant Activities of Formulated Agar from Brown Seaweed Laminaria digitata (Hudson) in Dimethyl Benzanthracene-Induced Swiss Albino Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jeneesha George ◽  
A. Thabitha ◽  
N. Vignesh ◽  
V. Manigandan ◽  
R. Saravanan ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Histopathological Examination ◽  
Brown Seaweed ◽  
Cancer Control ◽  
In Vitro Cytotoxicity ◽  
Control Group ◽  
High Dose ◽  
Laminaria Digitata ◽  
Group 2

This study explores the antiskin cancer effect of formulated agar (FA) from Laminaria digitata on dimethyl benzanthracene- (DMBA-) induced skin cancer mice. The agar was extracted and formulated (emulgel), and FA was biochemically characterized. The in vitro cytotoxicity of FA was tested using NTT 3T3 mice fibroblast cells. The mice were divided into 5 groups: group 1 served as control mice, group 2 mice were considered as DMBA-induced cancer control, group 3 mice were FA pretreated (low dose) + DMBA-induced mice, group 4 mice were FA pretreated (high dose) + DMBA-induced mice, and group 5 were positive control + DMBA-induced mice. The behaviour and biochemical markers of cancer were significantly decreased in group 2 (DMBA-induced) mice, which were brought to near normalcy by FA pretreated mice (groups 3 and 4). The levels of p53 and keratin were significantly elevated in group 2 mice and these levels were decreased in 3 and 4 mice as well. The histopathological examination of DMBA-induced mice was shown degenerated cervical patches in the skin, cirrhosis in liver, oedema in the renal tissue, and swollen and damage in cardiac tissue, which were reduced for the mice applied with FA. This confirms that FA pretreatment offered potential antiskin cancer property.

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

scholarly journals Taurine Attenuates Carcinogenicity in Ulcerative Colitis-Colorectal Cancer Mouse Model

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Guifeng Wang ◽  
Ning Ma ◽  
Feng He ◽  
Shosuke Kawanishi ◽  
Hatasu Kobayashi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Drinking Water ◽  
Mouse Model ◽  
Histopathological Examination ◽  
Tumor Formation ◽  
Water Model ◽  
Control Group ◽  
Ki 67

Taurine (2-aminoethane-sulfonic acid) is a type of amino acids and has numerous physiological and therapeutic functions, including anti-inflammation. However, there are few studies on the anticancer action of taurine. Our previous studies have demonstrated that taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells in vitro. In this study, we have investigated whether taurine has an anticancer effect, using azoxymethane (AOM)/sulfate sodium (DSS)- induced mouse model for colon carcinogenesis. All mice, except those in control group, received a single intraperitoneal injection of AOM and DSS in the drinking water for 7 days twice, with 1-week interval. After the first DSS treatment, mice were given distilled water (model group) or taurine in the drinking water (taurine group) ad libitum. No tumor was observed in the control group. Taurine significantly suppressed AOM+DSS-induced tumor formation. Histopathological examination revealed AOM/DSS treatment induced colon cancer in all mice (8/8, 100%), and taurine significantly inhibited the progression of colon cancer (4/9, 44.4%). Taurine significantly attenuated cell proliferation in cancer tissues detected by Ki-67 staining. Taurine significantly increased the levels of an apoptosis marker cleaved caspase-9 and tumor suppressor protein PTEN. This is the first study that demonstrated that taurine significantly reduced carcinogenicity in vivo using AOM/DSS-induced colon cancer mouse model.

scholarly journals In Vivo and In Vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 478 ◽  
Author(s):  
Rasha Al-Rikabi ◽  
Hanady Al-Shmgani ◽  
Yaser Hassan Dewir ◽  
Salah El-Hendawy
Keyword(s):  
Breast Cancer ◽  
Chromatin Condensation ◽  
Control Group ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Protective Effects ◽  
Mcf7 Cells ◽  
Tnf Α

(1) Background: Plant flavonoids are efficient in preventing and treating various diseases. This study aimed to evaluate the ability of hesperidin, a flavonoid found in citrus fruits, in inhibiting lipopolysaccharide (LPS) induced inflammation, which induced lethal toxicity in vivo, and to evaluate its importance as an antitumor agent in breast cancer. The in vivo experiments revealed the protective effects of hesperidin against the negative LPS effects on the liver and spleen of male mice. (2) Methods: In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH) and catalase (CAT), whereas in spleen, the concentration of cytokines including IL-33 and TNF-α was measured. The in vitro experiments including MTT assay, clonogenity test, and sulforhodamine 101 stain with DAPI (4′, 6-diamidino-2-phenylindole) were used to assess the morphological apoptosis in breast cancer cells. (3) Results: The results of this study revealed a significant increase in the IL-33 and TNF-α cytokine levels in LPS challenged mice along with a considerable elevation in glutathione (GSH); moreover, the catalase (CAT) level was higher compared to that of the control group. Cytotoxicity of the MCF-7 cell line revealed significant differences among the groups treated with different concentrations when compared to the control groups, in a concentration-dependent manner. Hesperidin significantly inhibited the colony formation of MCF7 cells when compared to that of control. Clear changes were observed in the cell shape, including cell shrinkage and chromatin condensation, which were associated with a later apoptotic stage. (4) Conclusion: The results indicate that hesperidin might be a potential candidate in preventing diseases.

scholarly journals Doxorubicin-induced myocardial failure in rats with malignant neoplasm: Protective role of fullerenol C60(OH)24

2008 ◽  
Vol 62 (3) ◽  
pp. 197-204 ◽  
Author(s):  
Rade Injac ◽  
Aleksandar Djordjevic ◽  
Borut Strukelj
Keyword(s):  
Untreated Control ◽  
Malignant Neoplasm ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Untreated Control Group ◽  
Cardiac Damage

The therapeutic utility of the anthracycline antibiotic doxorubicin is limited due to its cardiotoxicity. Our aim was to investigate the efficacy of fullerenol C60(OH)24 in preventing single, high-dose doxorubicin-induced cardiotoxicity in rats with malignant neoplasm. In vitro and in vivo studies have shown that fullerenol C60(OH)24, has strong antioxidative potential. Experiment was performed on adult female Sprague Dawley rats with chemically induced mammary carcinomas. All 32 rats (2-5 groups) received i.p. applications of 1-methyl-l-nitrosourea (MNU; 50 mg/kg body weight) on the 50th and 113th day of age. Animals were randomly divided into five groups as follows: (1) Untreated control group - rats received saline only; (2) Cancer control group - rats received MNU and saline; (3) Dox group - rats received MNU and Dox 8 mg/kg; (4) Full/Dox group -rats received MNU and Full 100 mg/kg 30 min before Dox 8 mg/kg; (5) Full group - rats received MNU and Full 100 mg/kg. Tumor incidence was 4.94 +- 0.576 per rat. The animals were sacrificed 2 days after the application of doxorubicin and/or fullerenol, and the serum activities of CK, LDH and ?-HBDH, as well as the levels of MDA, GSH, GSSG, GSH-Px, SOD, CAT, GR and TAS in the heart, were determined. The results obtained from the enzymatic activity in the serum show that the administration of a single dose of 8 mg/kg in all treated groups induces statistically significant damage. There are significant changes in the enzymes of LDH and CK (p < 0.05), after an i.p. administration of doxorubicin/fullerenol and fullerenol. Comparing all groups with untreated control group, point to the conclusion that in the case of a lower oc-HBDH/LDH ratio, results in more serious the liver parenchymal damage. The results revealed that doxorubicin induced oxidative damage and that the fullerenol antioxidative influence caused significant changes in MDA, GSH, GSSG, GSH-Px, SOD, CAT, GR and TAS level in the heart (p < 0.05). Ultra structural analysis of heart tissues from rats treated with doxorubicin and indicated that the hearts of the rats were protected from doxorubicin-induced subcellular damage. Doxorubicin/fullerenol rats did not appear to show significant cardiac damage although occasional focal loss of cristae in the mitochondria was observed. Therefore, it is suggested that fullerenol might be a potential cardioprotector in doxorubicin-treated individuals.

scholarly journals Evaluation of Arylimidamides DB1955 and DB1960 as Candidates against Visceral Leishmaniasis and Chagas' Disease:In VivoEfficacy, Acute Toxicity, Pharmacokinetics, and Toxicology Studies

2012 ◽  
Vol 56 (7) ◽  
pp. 3690-3699 ◽  
Author(s):  
Xiaohua Zhu ◽  
Qiang Liu ◽  
Sihyung Yang ◽  
Toufan Parman ◽  
Carol E. Green ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Histopathological Examination ◽  
Clinical Signs ◽  
Infection Model ◽  
High Dose ◽  
Repeat Dose ◽  
Dosing Regimen ◽  
Peak Parasitemia

ABSTRACTArylimidamides (AIAs) have shown outstandingin vitropotency against intracellular kinetoplastid parasites, and the AIA 2,5-bis[2-(2-propoxy)-4-(2-pyridylimino)aminophenyl]furan dihydrochloride (DB766) displayed goodin vivoefficacy in rodent models of visceral leishmaniasis (VL) and Chagas' disease. In an attempt to further increase the solubility andin vivoantikinetoplastid potential of DB766, the mesylate salt of this compound and that of the closely related AIA 2,5-bis[2-(2-cyclopentyloxy)-4-(2-pyridylimino)aminophenyl]furan hydrochloride (DB1852) were prepared. These two mesylate salts, designated DB1960 and DB1955, respectively, exhibited dose-dependent activity in the murine model of VL, with DB1960 inhibiting liver parasitemia by 51% at an oral dose of 100 mg/kg/day × 5 and DB1955 reducing liver parasitemia by 57% when given by the same dosing regimen. In a murineTrypanosoma cruziinfection model, DB1960 decreased the peak parasitemia levels that occurred at 8 days postinfection by 46% when given orally at 100 mg/kg/day × 5, while DB1955 had no effect on peak parasitemia levels when administered by the same dosing regimen. Distribution studies revealed that these compounds accumulated to micromolar levels in the liver, spleen, and kidneys but to a lesser extent in the heart, brain, and plasma. A 5-day repeat-dose toxicology study with DB1960 and DB1955 was also conducted with female BALB/c mice, with the compounds administered orally at 100, 200, and 500 mg/kg/day. In the high-dose groups, DB1960 caused changes in serum chemistry, with statistically significant increases in serum blood urea nitrogen, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase levels, and a 21% decrease in body weight was observed in this group. These changes were consistent with microscopic findings in the livers and kidneys of the treated animals. The incidences of observed clinical signs (hunched posture, tachypnea, tremors, and ruffled fur) were more frequent in DB1960-treated groups than in those treated with DB1955. However, histopathological examination of tissue samples indicated that both compounds had adverse effects at all dose levels.

scholarly journals Assessment The Efficacy of Thymol Against Toxocara Vitulorum In Experimentally Infected Rats

2021 ◽  
Author(s):  
Shawky M Aboelhadid ◽  
Sahar Abdel Aleem Abdel-Aziz
Keyword(s):  
Histopathological Examination ◽  
Treated Group ◽  
Control Group ◽  
Albino Rats ◽  
Untreated Control Group ◽  
Toxocara Vitulorum ◽  
The Third ◽  
Ifn Γ

Abstract The effect of thymol and ivermectin on the development and embryonation of Toxocara vitulorum (T. vitulorum) eggs, as well as their migration in albino rats was investigated in vitro. A total of forty male albino rats were divided into four groups for an in vivo experiment. The first group was uninfected; the second group was infected but left untreated; the third group received thymol at a dose of 40 mg/kg; and the fourth group received ivermectin (0.2 mg/kg). Thymol inhibited the development of Toxocara larvae within the eggs in vitro. Ivermectin; however, produced inconsistent results. The in vivo results indicated that the recovery rates of Toxocara larvae from the liver and lungs on day 7 post-infection were significantly lower in the thymol- or ivermectin-treated group than in the infected untreated control group. Histopathological examination demonstrated that thymol and ivermectin were effective in reducing larval load, reducing the number and size of granulomas in the absence of larvae, and improving tissue architectures. Albumin levels were significantly increased in the thymol-treated group. Nitric oxide, IL-4, and IFN- γ levels were significantly decreased in the serum of the thymol- or ivermectin-treated group. The current study concluded that thymol possessed anti-Toxocara activity in a rat model. Additionally, thymol possessed ovicidal properties and may be used as a disinfectant.

scholarly journals Potential Mechanisms Responsible for the Antinephrolithic Effects of an Aqueous Extract of Fructus Aurantii

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaoran Li ◽  
Qiang Liang ◽  
Yunji Sun ◽  
Long Diao ◽  
Ze Qin ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Significant Inhibition ◽  
Control Group ◽  
High Dose ◽  
Crystal Formation ◽  
Crystal Dissolution ◽  
Therapeutic Groups ◽  
Immunohistochemical Analyses

The potential effects of Fa extract on the prevention and treatment of CaOx nephrolithiasis were analyzed in an ethylene glycol- (EG-) induced CaOx crystallization model in rats and anin vitroassay. Multiple biochemical variables were measured in the urine and kidney. Kidney sections were subjected to histopathological and immunohistochemical analyses. Urolithiasis-related osteopontin (OPN) was evaluated by Western blotting. Thein vitroassay revealed the significant inhibition of crystal formation (3.50±1.43) and dilution of formed crystals (12.20±3.35) in the group treated with 1 mg/mL Fa extract compared with the control group (52.30±4.71and53.00±4.54, resp.) (p<0.05). Thein vivoexperiments showed that prophylactic treatment with Fa aqueous extract significantly prevented EG-induced renal crystallization and pathological alterations compared with nephrolithic rats (p<0.05). Significantly lower levels of oxidative stress, oxalate, and OPN expression as well as increased citrate and urine output levels were observed in both the low- and high-dose prophylactic groups (p<0.05). However, in the low- and high-dose therapeutic groups, none of these indexes were significantly improved (p>0.05) except for urinary oxalate in the high-dose therapeutic groups (p<0.05). Fa extract prevented CaOx crystallization and promoted crystal dissolutionin vitro. Additionally, it was efficacious in preventing the formation of CaOx nephrolithiasis in rats.

scholarly journals Neferine induces mitochondrial dysfunction to exert anti-proliferative and anti-invasive activities on retinoblastoma

2020 ◽  
Vol 245 (15) ◽  
pp. 1385-1394
Author(s):  
Jing Wang ◽  
Yanmin Dong ◽  
Qiuming Li
Keyword(s):  
Tumor Volume ◽  
Significant Inhibition ◽  
Control Group ◽  
High Dose ◽  
Tumor Weight ◽  
New Treatment ◽  
Xenotransplantation Model

Retinoblastoma is common primary intraocular malignancy of infants and childhood. Neferine is a major bisbenzylisoquinoline alkaloid derived from the lotus plumule in Nelumbo nucifera. This study evaluated the mitigation role of Neferine on retinoblastoma in vitro and in vivo. Xenotransplantation model was established by injecting WERI-Rb-1 cells subcutaneously. Upon induction of retinoblastoma , mice were intraperitoneally injected with Neferine (0, 0.5, 1, 2 mg/kg) or ethanol every 3 days for 30 days. Tumor weight and tumor volume were measured every three days and compared between four groups. Then, mice were sacrificed and immunohistochemical examination was performed to compare Ki67, VEGF content between groups. WERI-Rb-1 cells were used for in vitro experiments and the anti-angiogenic role of Neferine was assessed by analyzing nodes/HPF number. In WERI-Rb-1 xenotransplantation model, compared with control group, 1 mg/kg Neferine treatment significantly inhibited tumor weight (0.39 ± 0.04 g vs. 0.25 ± 0.03 g, P< 0.05) and tumor volume (2163 ± 165 mm3 vs. 1276 ± 108 mm3, P< 0.05) after 30 days. Compared with ethanol-injected mice, 2 μM Neferine treatment significantly enhanced apoptosis rate (2.1 ± 0.6% vs. 14.6 ± 2.6%, P< 0.05), accompany downregulation of Ki67 (0.09 ± 0.02% vs. 0.01 ± 0.004%, P< 0.05) and VEGF (0.28 ± 0.04% vs. 0.05 ± 0.03%, P< 0.05) expression. Additionally, 2 μM Neferine treatment significantly decreased JC-1 red/green percentage. High-dose Neferine could decrease retinoblastoma angiogenesis in association with a significant inhibition on tumor growth and invasion. These findings suggested that Neferine could be a new treatment or adjuvant against retinoblastoma.

scholarly journals Treatment of Non-Alcoholic Steatosis: Preclinical Study of a New Nutraceutical Multitarget Formulation

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1819
Author(s):  
Laura Micheli ◽  
Alessandra Pacini ◽  
Lorenzo Di Cesare Mannelli ◽  
Elena Trallori ◽  
Roberta D’Ambrosio ◽  
...  
Keyword(s):  
Control Group ◽  
High Dose ◽  
Standard Diet ◽  
Dependent Manner ◽  
Post Injury ◽  
In Vivo Models ◽  
Pathologic Features ◽  
Anti Inflammatory

Multifactorial pathogenesis of non-alcoholic steatohepatitis (NASH) disease, a wide-spread liver pathology associated with metabolic alterations triggered by hepatic steatosis, should be hit by multitarget therapeutics. We tested a multicomponent food supplement mixture (AP-NHm), whose components have anti-dislipidemic, antioxidant and anti-inflammatory effects, on in vitro and in vivo models of NASH. In vitro, hepatic cells cultures were treated for 24 h with 0.5 mM oleic acid (OA): in the co-treatment set cells were co-treated with AP-NH mixtures (AP-NHm, 1:3:10 ratio) and in the post-injury set AP-NHm was added for 48 h after OA damage. In vivo, C57BL/6 mice were fed with high-fat diet (HFD) for 12 weeks, inducing NASH at 7th week, and treated with AP-NHm at two dosages (1:3 ratio) in co-treatment or post-injury protocols, while a control group was fed with a standard diet. In in vitro co-treatment protocol, alterations of redox balance, proinflammatory cytokines release and glucose uptake were restored in a dose-dependent manner, at highest dosages also in post-injury regimen. In both regimens, pathologic dyslipidemias were also ameliorated by AP-NHm. In vivo, high-dose-AP-NHm-co-treated-HFD mice dose-dependently gained less body weight, were protected from dyslipidemia, and showed a lower liver weight. Dose-dependently, AP-NHm treatment lowered hepatic LDL, HDL, triglycerides levels and oxidative damage; co-treatment regimen was anti-inflammatory, reducing TNF-α and IL-8 levels. Hepatic lipidic infiltration significantly decreased in co-treated and post-injury-AP-NHm-HFD animals. The multitarget approach with AP-NHm was effective in preventing and reducing NASH-related pathologic features, warranting for the clinical development of this compound.

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