Antiproliferative and Apoptotic Effects of Shemamruthaa, a Herbal Preparation, in 7,12-Dimethylbenz(a)Anthracene-Induced Breast Cancer Rats

2015 ◽  
Vol 20 (4) ◽  
pp. 259-268 ◽  
Author(s):  
Ayyakkannu Purushothaman ◽  
Elumalai Nandhakumar ◽  
Palanivelu Shanthi ◽  
Thiruvaiyaru Panchanatham Sachidanandam

A herbal preparation, Shemamruthaa (SM), was formulated to investigate the molecular mechanism by which it exhibits anticancer effects in mammary carcinoma bearing rats. Female Sprague-Dawley rats were used for the study, and mammary carcinoma was induced by administration of 7,12-dimethylbenz( a)anthracene, intragastrically. After 3 months of induction period, the rats were treated with SM (400 mg/kg body weight) for 14 days. Our study shows that SM-treated mammary carcinoma rats showed regression in tumor volume with concomitant increase in p53, Bax, caspase-3, and caspase-9 mRNA and protein levels compared with mammary carcinoma–induced rats. Proliferating cell nuclear antigen and anti-apoptotic Bcl-2 were markedly increased in mammary carcinoma–induced rats, whereas the SM treatment significantly decreased the expression of these proteins. The expression pattern of apoptotic signaling molecules analyzed in the present study signifies the therapeutic efficacy of SM against breast cancer.

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Deena Priscilla Henry ◽  
Jasmine Ranjan ◽  
Rajesh Kumar Murugan ◽  
Annapoorani Sivanantham ◽  
Manikandan Alagumuthu

Abstract Background Plant extracts are effectively acting as the natural medicinal cocktail, non-side effective, efficacious, and freely available. The present study aimed to unveil the pharmacological and medicinal effects of Terminalia chebula plant extract in 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Sprague Dawley rats. The plant extract obtained was subjected to in vivo antioxidant and anticancer studies in various concentrations after an analytical technique such as FTIR, GCMS, and HPLC-based chemo-profiling in Sprague Dawley rats. Results Apart from the antiproliferative effect on breast cancer cell line (MCF-7) and normal breast epithelial cells (MCF-10a), we have measured the changes in body weight, along with other tumor parameters such as tumor volume, tumor incidence, tumor weight, tumor burden, serum biochemical parameters, and histopathological findings of breast tissue. As the oxidative stress further enhances the development of cancer, the antioxidant property of the plant extract demonstrates its use against cancer treatment. One hundred fifty milligrams per milliliter (IC50 250 μg/mL) concentration of the ethanolic extract was vital for the proliferation of MCF-7 cell lines (Fig. 7a). Meanwhile, 300 μg/mL (IC50 150 μg/mL) was an effective dose to attain a maximum HDAC inhibition of 78%. Also, the normal liver and kidney functioning revealed the non-toxicity nature of the plant. Conclusion Terminalia chebula could be one of the effective naturally obtained anti-breast cancer medications. Isolation and characterization of individual bioactive compounds of T. chebula would be the future perspective.


Author(s):  
Karthick Dharmalingam ◽  
Stalin Ramakrishnan ◽  
Sachidanandam Panchanatham ◽  
Shanthi Palanivelu*

ABSTRACTObjective: To study the restorative effect of Tridham (TD) and 1,2,3,4,6-penta-o-galloyl-β-D-glucose (PGG) on 7,12-dimethyl benz(a)anthracene(DMBA)-induced mammary carcinoma in female Sprague-Dawley rats.Methods: Rats were divided into seven groups of six animals each. Group I rats served as control. Group II - mammary carcinoma was inducedby DMBA. Group III and Group IV were induced with DMBA and subsequently treated with TD and PGG, respectively, for 48 days. Group V wastreated with DMBA and subsequently with a standard drug, cyclophosphamide (CYC). Group VI and Group VII were given TD and PGG alone,respectively, for 48 days. After the experimental period, the levels of lipid peroxides (LPO), activities of enzymic and non-enzymic antioxidantssuch as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, reduced glutathione, vitamin C, and vitamin E wereevaluated in the breast tissue of control and experimental rats. Levels of LPO, marker enzymes such as 5’-nucleotidase and lactate dehydrogenase,were also evaluated.Results: The levels of enzymic and non-enzymic antioxidants were decreased in DMBA-induced rats when compared to control rats. The levels oftumor markers were increased in DMBA-induced rats when compared to control rats. These parameters were restored to near normal levels ontreatment with TD and PGG.Conclusions: The results suggest that TD and PGG have a cytoprotective role in DMBA-induced breast cancer-bearing rats. The effect of TD and PGGwas found to be more pronounced than CYC, a standard drug.Keywords: Breast cancer, Tridham, Penta galloyl glucose, Antioxidants, Tumor markers, Sprague-Dawley rats.


2021 ◽  
pp. 1-9
Author(s):  
Guizhen Liu ◽  
Yuchuan Sun ◽  
Fei Liu

<b><i>Objective:</i></b> The purpose of this study was to explore the role of curcumin (Cur) in isoflurane (ISO)-induced learning and memory dysfunction in Sprague-Dawley rats and further elucidate the mechanism of the protective effect produced by Cur. <b><i>Methods:</i></b> Rat models of cognitive impairment were established by inhaling 3% ISO. The Morris water maze test was used to assess the cognitive function of rats. ELISA and qRT-PCR were used to analyze the protein levels of pro-inflammatory cytokines and expression levels of miR-181a-5p, respectively. <b><i>Results:</i></b> Cur significantly improved the ISO-induced cognitive dysfunction in rats and alleviated the ISO-induced neuroinflammation. miR-181a-5p was overexpressed in ISO-induced rats, while Cur treatment significantly reduced the expression of miR-181a-5p. Overexpression of miR-181a-5p promoted the cognitive impairment and the release of inflammatory cytokines and reversed the neuroprotective effect of Cur. <b><i>Conclusion:</i></b> Cur has a protective effect on ISO-induced cognitive dysfunction, which may be achieved by regulating the expression of miR-181a-5p.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Na Cui ◽  
Hao Wang ◽  
Yun Long ◽  
Longxiang Su ◽  
Dawei Liu

The aim of this study is to determine the mechanism of sepsis-induced vascular hyperpermeability and the beneficial effect of glucocorticoid in protecting vascular endothelium. Male Sprague-Dawley rats were given either a bolus intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli055:B5, 10 mg/kg, Sigma) or vehicle (pyrogen-free water). Animals of treatment groups were also given either dexamethasone (4 mg/kg, 30 min prior to LPS injection) or the matrix metalloproteinases (MMPs) inhibitor doxycycline (4 mg/kg, 30 min after LPS injection). Both activities and protein levels of MMP-2p<0.001and MMP-9p<0.001were significantly upregulated in aortic homogenates from LPS-treated rats, associated with decreased ZO-1p<0.001and syndecan-1p=0.011protein contents. Both dexamethasone and doxycycline could significantly inhibit MMPs activity and reserve the expressions of ZO-1 and syndecan-1. The inhibition of MMPs by dexamethasone was significantly lower than that by doxycycline, while the rescue of syndecan-1 expression from LPS-induced endotoxemic rat thoracic aorta was significantly higher in the dexamethasone-treated compared to the doxycycline-treatedp=0.03. In conclusion, activation of MMPs plays important role in regulating ZO-1 and syndecan-1 protein levels in LPS mediated endothelial perturbation. Both dexamethasone and doxycycline inhibit activation of MMPs that may contribute to the rescue of ZO-1 and syndecan-1 expression.


2017 ◽  
Vol 92 ◽  
pp. 207-214 ◽  
Author(s):  
Kalyani Chowdary Karnam ◽  
Maheswara Ellutla ◽  
Lakshmi Narendra Bodduluru ◽  
Eshvendar Reddy Kasala ◽  
Shravan Kumar Uppulapu ◽  
...  

2000 ◽  
Vol 89 (4) ◽  
pp. 1483-1490 ◽  
Author(s):  
William G. Schrage ◽  
Christopher R. Woodman ◽  
M. Harold Laughlin

The purpose of this study was to test the hypothesis that endothelium-dependent dilation is impaired in soleus resistance arteries from hindlimb-unweighted (HLU) rats. Male Sprague-Dawley rats (300–350 g) were exposed to HLU ( n = 14) or weight-bearing control (Con, n = 14) conditions for 14 days. After the 14-day treatment period, soleus first-order (1A) arterioles were isolated and cannulated with micropipettes to assess vasodilator responses to an endothelium-dependent dilator, ACh (10−9–10−4 M), and an endothelium-independent dilator, sodium nitroprusside (SNP, 10−9–10−4 M). Arterioles from HLU rats were smaller than Con arterioles (maximal passive diameter = 140 ± 4 and 121 ± 4 μm in Con and HLU, respectively) but developed similar spontaneous myogenic tone (43 ± 3 and 45 ± 3% in Con and HLU, respectively). Arteries from Con and HLU rats dilated in response to increasing doses of ACh, but dilation was impaired in arterioles from HLU rats ( P = 0.03), as was maximal dilation to ACh (85 ± 4 and 65 ± 4% possible dilation in Con and HLU, respectively). Inhibition of nitric oxide (NO) synthase (NOS) with N ω-nitro-l-arginine (300 μM) reduced ACh dilation by ∼40% in arterioles from Con rats and eliminated dilation in arterioles from HLU rats. The cyclooxygenase inhibitor indomethacin (50 μM) did not significantly alter dilation to ACh in either group. Treatment with N ω-nitro-l-arginine + indomethacin eliminated all ACh dilation in Con and HLU rats. Dilation to sodium nitroprusside was not different between groups ( P = 0.98). To determine whether HLU decreased expression of endothelial cell NOS (ecNOS), mRNA and protein levels were measured in single arterioles with RT-PCR and immunoblot analysis. The ecNOS mRNA and protein expression was significantly lower in arterioles from HLU rats than in Con arterioles (20 and 65%, respectively). Collectively, these data indicate that HLU impairs ACh dilation in soleus 1A arterioles, in part because of alterations in the NO pathway.


2014 ◽  
Vol 87 (2) ◽  
pp. 263-276 ◽  
Author(s):  
Shanna J. Smith ◽  
Long Gu ◽  
Elizabeth A. Phipps ◽  
Lacey E. Dobrolecki ◽  
Karla S. Mabrey ◽  
...  

1974 ◽  
Vol 11 (2) ◽  
pp. 153-164 ◽  
Author(s):  
J. E. Gray ◽  
R. N. Weaver ◽  
A. Purmalis

The kidneys of 43 male Sprague-Dawley rats, mostly 12-18 months old, were examined by electron microscopy. Paraffin sections stained with the allochrome procedure and thick epoxy sections stained with toluidine blue were used to select sites of nephrotic changes. Protein levels in urine were monitored periodically. The basement membranes of affected nephrons showed a two- to threefold thickening in the capillary loops and Bowman's capsule. Epithelial cells in the glomeruli underwent compensatory changes of hypertrophy, fusion of foot processes and occasionally microvillar transformation. Dense granular material as well as protein absorption droplets formed in the epithelial cells. Epithelial cells of proximal convolutions atrophied and disappeared as the basement membrane thickened to several micrometers. An increase of dense bodies, granular material, and focal cytoplasmic degradation was observed in these cells. The ongoing irreversible deterioration of scattered nephrons suggested the designation of chronic progressive nephrosis for this common disease of Sprague-Dawley rats over 1 year old.


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