3,3′-Diindolylmethane Encapsulated Chitosan Nanoparticles Accelerates Inflammatory Markers,ER/PR,Glycoprotein and Mast Cells Population During Chemical Carcinogen Induced Mammary Cancer in Rats

The present study aimed to investigate the effect of 3,3′-diindolylmethane (DIM) on inflammatory markers, estrogen receptors (ER), progesterone receptors (PR), level of glycoprotein and the mast cell population in 7,12-dimethylbenz (a) anthracene (DMBA) 25 mg/kg b.wt. induced rat mammary carcinogenesis. After 8 weeks of tumor formation, rats had access to an oral administrated with DIM 10 mg/kg b.wt. and DIM@CS-NP 0.5 mg/kg body weight respectively for 8 weeks. The oral administration of DIM@CS-NP 0.5 mg/kg b.wt. suppressed the Cox-2, NF-κB and TNF-α protein expression on DMBA induced rats compared to DIM 10 mg/kg b.wt. The ER/PR levels were increased on DMBA induced rats, treated with DIM@CS-NP 0.5 mg/kg b.wt. reduced ER/PR level as well as glycoprotein and mast cell population than DIM 10 mg/kg b.wt. The result shows that, DIM@CS-NP 0.5 mg/kg b.wt. has the potentially inhibit abnormal levels of inflammatory markers, ER, PR, levels of glycoprotein and mast cell population compared to DIM 10 mg/kg b.wt.     

Potential Chemoprevention of 7,12-Dimethylbenz[a]anthracene Induced Renal Carcinogenesis by Moringa oleifera Pods and Its Isolated Saponin

Present investigation shows that hydroethanolic extract of Moringa oleifera (MOHE) and its isolated saponin (SM) attenuates DMBA induced renal carcinogenesis in mice. Isolation of SM was achieved by TLC and HPLC and characterization was done using IR and ¹H NMR. Animals were pre-treated with MOHE (200 and 400 mg/kg body weight; p.o), BHA as a standard (0.5 and 1 %) and SM (50 mg/kg body weight) for 21 days prior to the administration of single dose of DMBA (15 mg/kg body weight). Administration of DMBA significantly (p < 0.001) enhanced level of xenobiotic enzymes. It enhanced renal malondialdehyde, with reduction in renal glutathione content, antioxidant enzymes and glutathione-S-transferase. The status of renal aspartate transaminase, alanine transaminase, alkaline phosphatase and total protein content were also found to be decreased along with increase in total cholesterol in DMBA administered mice. Pretreatment with MOHE and SM significantly reversed the DMBA induced alterations in the tissue and effectively suppressed renal oxidative stress and toxicity.     

Protective Effect of Allyl Isothiocyanate on Glycoprotein Components in 7,12-dimethylbenz(a)anthracene Induced Mammary Carcinoma in Rats

The present study aimed to investigate the protective effect of allyl isothiocyanate (AITC) on glycoprotein components in 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in female Sprague–Dawley rats. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near mammary gland. The levels of glycoprotein components such as hexose, hexosamine and sialic acid were analyzed colorimetrically in plasma, mammary and liver tissues. We observed an increased levels of glycoprotein components in plasma, mammary and liver tissues in cancer bearing rats. It was further confirmed by Periodic Acid Schiff staining in mammary and liver tissues. Upon oral administration of AITC to DMBA injected rats, the abnormal changes were reverted back to near normal levels and biochemical findings are supported by histological analysis. This could be due to the anti-neoplastic potential of AITC against DMBA-induced mammary carcinogenesis. The result shows that AITC has the potential to inhibit abnormal glycosylation that favors neoplastic transformation.     

Modulation of Angiogenesis,Proliferative Response and Apoptosis by β-Sitosterol in Rat Model of Renal Carcinogenesis

As expanded understanding of molecular tumor characteristics, which drive renal cancer growth and progression gives a promising future for renal carcinoma therapy. The objective of the present study was designed to examine the effect of β-sitosterol on a rat model of experimental renal carcinogenesis. Renal carcinogenesis was induced in rats treated with N-diethylnitrosamine (DEN; 200 mg/kg bw single i.p., injection) and ferric nitrilotriacetate (Fe-NTA; 9 mg Fe/kg bw i.p., twice a week for 16 weeks). β-sitosterol pretreatment (20 mg/kg bw in 0.1 % carboxymethyl cellulose (CMC) p.o., thrice a week for 24 weeks) was started 2 weeks before the exposure to carcinogens. Expression of angiogenesis marker (VEGF), proliferative markers (cyclin D1, PCNA) and apoptotic markers (Bcl-2, Bax, caspase-3 and caspase-9) were analyzed to assess the anti-cancer potential of β-sitosterol in renal carcinogenesis model. mRNA and protein expression changes were determined by qRT-PCR, Western blotting, ELISA technique and immunohistochemistry. Our results showed that oral administration of β-sitosterol pretreatment significantly (P < 0.05) reversed the expression of all the above mentioned markers and histological features which have been modified by renal carcinogen. It is concluded that, the protective effects of β-sitosterol against renal cancer is associated with the induction of apoptosis and the inhibition of cellular proliferation.     

Exploring the Potential Role of Chemopreventive Agent,Hesperetin Conjugated Pegylated Gold Nanoparticles in Diethylnitrosamine-Induced Hepatocellular Carcinoma in Male Wistar Albino Rats

Liver cancer is the fifth most common cancer and is still one of the leading causes of death world wide, due to food additives, alcohol, fungal toxins, air, toxic industrial chemicals, and water pollutants. Chemopreventive drugs play a potential role in liver cancer treatment. Obviously in the production of anticancer drugs, the factors like poor solubility, bioavailability, biocompatibility, limited chemical stability, large amount of dose etc., plays a major role. Against this backdrop, the idea of designing the chemopreventive nature of bio flavanoid hesperetin (HP) drug conjugated with pegylated gold nanoparticles to increasing the solubility, improve bioavailability and enhance the targeting capabilities of the drug during diethylnitrosamine (DEN) induced liver cancer in male wistar albino rats. The dose fixation studies and the toxicity of pure HP and HP conjugated gold nanoparticles (Au-mPEG₍₅₀₀₀₎-S-HP) were analysed. After concluded the dose fixation and toxicity studies the experimental design were segregated in six groups for the anticancer analysis of DEN induced HCC for 16 weeks. After the experimental period the body weight, relative liver weight, number of nodules and size of nodules, the levels of tumor markers like CEA, AFP and the level of lipid peroxidation, lipid hydroperoxides and the activities of antioxidant enzymes were assessed. The administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma glutamyl transpeptidase. The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase, catalase, reduced glutathione, glutathione peroxidise, and glutathione reductase. HP supplementation (20 mg/kg b.wt) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer and the HP loaded gold nanoparticels (Au-mPEG₍₅₀₀₀₎-S-HP) treated animals shows the better treatment than the pure HP due to the solubility of drug, bioavailability and the target drug delivery of the biodegradable polymer. Histological observations were also carried out, which added supports to the chemopreventive action of the pure HP and HP loaded gold nanoparticles (Au-mPEG₍₅₀₀₀₎-S-HP) against DEN induction during liver cancer progression. These findings suggest that HP loaded gold nanoparticels (Au-mPEG₍₅₀₀₀₎-S-HP) shows better efficacy than the pure HP against lipid peroxidation, hepatic cell damage and protects the antioxidant system in DEN induced hepatocellular carcinogenesis.     

Status and Interrelationship of Zinc,Copper, Iron,Calcium and Selenium in Prostate Cancer

Deficiency or excess of certain trace elements has been considered as risk factor for prostate cancer. This study was aimed to detect differential changes and mutual correlations of selected trace elements in prostate cancer tissue versus benign prostatic hyperplasia tissue. Zinc, copper, iron, calcium and selenium were analysed in histologically proven 15 prostate cancer tissues and 15 benign prostatic hyperplasia tissues using atomic absorption spectrophotometer. Unpaired two tailed t test/Mann–Whitney U test and Pearson correlation coefficient were used to compare the level of trace elements, elemental ratios and their interrelations. As compared to benign prostatic tissue, malignant prostatic tissue had significantly lower selenium (p = 0.038) and zinc (p = 0.043) concentrations, a lower zinc/iron ratio (p = 0.04) and positive correlation of selenium with zinc (r = 0.71, p = 0.02) and iron (r = 0.76, p = 0.009). Considerably divergent interrelationship of elements and elemental ratios in prostate cancer versus benign prostatic hyperplasia was noted. Understanding of differential elemental changes and their interdependence may be useful in defining the complex metabolic alterations in prostate carcinogenesis with potential for development of element based newer diagnostic, preventive and therapeutic strategies. Further studies may be needed to elucidate this complex relationship between trace elements and prostate carcinogenesis.     

Effect of Sodium Chloride on Efficiency of Cisplatinum Dissolved in Dimethyl Sulfoxide: An In Vitro Study

Cisplatinum (Cispt) is an anti-cancer drug with a low level of solubility. One of Cispt’s solvents is dimethyl sulfoxide (DMSO) which can be substituted with chlorine of drug as Cispt’s solvent. Applying such a solvent in biological studies is impossible due to intense reduction in activity. On the other hand, it is specified that Cispt’s stability is increased in aqueous media by increasing sodium chloride (NaCl) concentration up to 0.9 %. Consequently, we intended to study the effect of DMSO on cytotoxicity of Cispt in presence of sodium. MTT assay was employed to study cytotoxicity effect of Cispt + NaCl + DMSO and Cispt + DMSO on G-292 cell line. Cytotoxicity in dilutions of 300 and 9 (p < 0.01) of Cispt in Cispt + NaCl + DMSO formulation was equal to 78 and 7 %. These values were estimated 79 and 18 % for Cispt + DMSO formulation and 79 and 24 % for free drug. IC50 values demonstrated reduction of 45 % in cytotoxicity of Cispt in Cispt + DMSO formulation. Studying chemical structure of Cispt and Cispt dissolved in DMSO showed that NaCl cannot inhibit inactivating effect of DMSO on Cispt and effect of this solvent on Cispt is independent from presence of NaCl. Results represented that using NaCl does not result in stability and keeping cytotoxicity properties of Cispt in DMSO. Findings suggest more studies for using DMSO as a solvent of Cispt.     

Evaluation of Antioxidants in the Kidney of Streptozotocin Induced Diabetic Rats

Diabetes mellitus is one of the most common endocrine metabolic disorders. Dual endocrine deficits of impaired insulin action (insulin resistance) and inadequate insulin secretion create an environment of chronic hyperglycemia and general metabolic disarray. Oxidative stress plays an important role in diabetic pathogenesis. Oxidative stress induced by streptozotocin (STZ) has been shown to damage pancreatic beta cell and produce hyperglycemia in rats. The present study was made to evaluate the antioxidant activity of ethanolic extract of the Evolvulus alsinoides in STZ induced rats. The antioxidant activities were done by using standard protocols. For histopathological analysis, the pancreatic tissues of all experimental groups were fixed with 10 % formalin for 24 h then the samples were stained with hematoxylin–eosin for the microscopic observation. Our results showed the significant decrease in lipid peroxidation and increases in the antioxidant (both enzymatic and nonenzymatic) levels after treatment with standard as well as the E. alsinoides. There is no significant difference between control and plant alone group rats. The histopathology reports also revealed non-toxic effect and protective effect of E. alsinoides in the kidney of STZ induced diabetic rats. Our result indicated that the E. alsinoides extract effectively increased the antioxidant level thereby it prevents oxidative stress during diabetes mellitus and also it showed the protective effect on kidney of STZ induced rats. Hence it can be used to maintain the antioxidant level during diabetes mellitus.     

Experimental Validation of Antidiabetic Potential of <Emphasis Type="Italic">Cayratia trifolia</Emphasis> (L.) Domin: An Indigenous Medicinal Plant

The present study was undertaken to evaluate antidiabetic and antioxidant activities of Cayratia trifolia root extract against streptozotocin induced diabetes in experimental rats to scientifically validate its use against diabetes in some parts of India. Ethanolic extract, showing the highest activity in in vitro experiments, was prepared in saline and administered orally to streptozotocin induced albino Wistar diabetic rats for 21 days. Biochemical parameters liver and muscles glycogen and in vivo antioxidant activity in normal, diabetic control, standard (metformin) and treated animals were determined and compared. Attempt was made to isolate, purify and characterize one of the major secondary metabolites in extract by range of chromatographic and spectroscopic techniques. Treatment of streptozotocin induced diabetic rats with ethanolic root extract (500 mg/kg) caused significant (P < 0.01) reduction in blood glucose (312–178 mg/dL), increase in body weight (181–219 g) and serum insulin (1.28–2.26 IU/dL). It also maintained lipid profile and tests of liver and kidney functions within normal range as compared to diabetic control rats and almost at par with standard drug metformin. The oxidative stress induced decline in glutathione and catalase in liver and kidney tissues showed recovery nearly to normal level as a function of treatment. The GC–MS profile of the extract showed relatively high concentration of β-sitosterol which was characterized by different spectroscopic and chromatographic techniques. The result scientifically and comprehensively validate the reported use of roots of this indigenous plant against diabetes. A strong antioxidant activity of the ethanolic root extract suitably compliments the antidiabetic effect.     

Effect of vitamin E on protein bound carbhohydrate complexes in radiation treated oral squamous cell carcinoma patients

Serum glycoproteins were evaluated in oral squamous cell carcinoma patients treated with radiotherapy and also the effect of vitamin E was studied. Cell surface glycoconjugates are important parameters in the detection of malignancy. Thus, the objective of the present study is to evaluate the efficacy of vitamin E on glycoproteins in oral cavity cancer patients treated with radiotherapy. The study includes 26 age and sex matched normal healthy individuals and 26 patients with squamous cell carcinoma of oral cavity. These patients were divided into two groups, one for radiotherapy alone (at a dosage of 6000 cGy in five fractions per week for a period of six weeks) and the other for radiotherapy plus vitamin E supplementation (at a dosage of 400 IU / day of vitamin E) for the entire period of radiotherapy. Levels of hexose, hexosamine, fucose and sialic acid were increased in oral squamous cell carcinoma patients and a significant decrease was observed in radiation treated patients when compared to control. The levels of glycoconjugates were significantly decreased in radiation treated patients supplemented with vitamin E. This measurement may be useful in assessing disease progression and identifying patients resistant to therapy and a possible role of vitamin E on reduction in glycoconjugate levels of radiation treated oral squamous cell carcinoma patients.     

Antioxidant and Anticancer Activities of Selected Persian Gulf Algae

In the present study, the effect of red (Gracillaria corticata), green (Ulva fasciata) and brown (Sargassum ilicifolium) seaweeds alcoholic extract, against five important human cancer cell lines (MCF-7, MDA-MB-231, HeLa, HepG2, and HT-29) proliferation, apoptosis and cell cycle arrest were evaluated. The reducing activity and total polyphenol content were also investigated. MTT assay was used for cytotoxicity test. Morphological alterations were examined using phase contrast, fluorescent and electron microscopy. All the extracts were antiproliferative against all the cancer cell lines, dose-dependently, with G. corticata methanol extract (GCME) having the greatest inhibition activity against MCF-7 cell line. The percentage of apoptosis increased from 18 to 78 %. The cell cycle analysis also showed that GCME can induce apoptosis which confirm by TEM. Algal extract reducing activities were as follows: G. corticata > S. ilicifolium > U. fasciata. The GCME is a good source of potential complementary and alternative functional food for prevention and treatment of cancer.     

Preparation,Characterization and Cytotoxic Effects of Pegylated Nanoliposomal Containing Carboplatin on Ovarian Cancer Cell Lines

Carboplatin is a chemotherapeutic agent used against various malignancies such as ovarian carcinoma. The aim of this study is to improve the therapeutic efficacy of carboplatin using pegylated liposomal nanocarriers. Nanoparticles were synthesized using thin film hydration technique and characterized for shape morphology, particle size, zeta potential and drug-release properties. In the next step, A2780S and A2780CP ovarian cancer cell lines were used to determine the efficacy of nanodrug by MTT assay. The particle size and zeta potential of nanodrug were measured 244.3 ± 19.6 nm and ?22.9 ± 1.7 mV, respectively. High encapsulation capacity (78.6 ± 3.7 %) confirmed the efficiency of technique. The cytotoxicity results also showed that nanodrug compared to free drug improve the efficacy of carboplatin against both A2780S (P < 0.01) and A2780CP (P < 0.05) cell lines. In conclusion, the findings of our study suggested pegylated liposomal nanocarriers are proper for carboplatin delivery to ovarian cancer cell lines A2780S and A2780CP.     

Experimental Validation of Antidiabetic and Antioxidant Potential of <Emphasis Type="Italic">Cassia tora</Emphasis> (L.): An Indigenous Medicinal Plant

The present study was undertaken to evaluate antidiabetic and antioxidant activities of Cassia tora (C. tora) seeds extract against streptozotocin induced diabetes in experimental rats to scientifically validate its use against diabetes. Ethanolic extract of C. tora seeds extract and standard drug (glibenclamide) prepared in aqueous gum acacia (2 %, w/v) suspension and fed orally to streptozotocin induced male adult diabetic rats of Charles Foster strain for 15 days. Biochemical parameters in normal, diabetic control, standard (600 μg/kg bw p.o.) and treated (500 mg/kg bw p.o.) animal groups were quantified and compared. Treatment of streptozotocin induced diabetic rats with ethanolic seeds extract caused significant (p < 0.001) reduction in blood glucose (270–220 mg/dl), total cholesterol (140–104 mg/dl), triglyceride (149–99 mg/dl), phospholipids (100–74 mg/dl), free fatty acid (2.39–2.00 μmol/l), lipid peroxide (9–5.63 nmol MDA/dl) and significantly increased post heparin lipolytic activity (11–14 nmol FFA released/h/l plasma) (p < 0.001). Furthermore, the seeds extract (100–400 μg) when tested for its antioxidant activity in vitro, showed significant (p < 0.001) inhibition in the generation of super oxide anions in enzymic system a (46–37, 33, 23, 21 nmol uric acid formed/min), in enzymic system b (113–91, 77, 60, 51 nmol formazon formed/min), non-enzymic system (324–230, 211, 161, 141 nmol uric acid formed/min) and hydroxyl radicals in enzymic system (544–501, 411, 319, 291 nmol 2,3-dihydroxybenzoate formed/h) and non-enzymic system (28–21, 17, 14, 12). The results of the present study demonstrated antidiabetic, antidyslipidemic and antioxidant activities of C. tora seeds which could help in prevention of diabeticdyslipidemia and related complications.     

Metabolic Issues in Schizophrenic Patients Receiving Antipsychotic Treatment

Schizophrenia is a psychotic disorder with a complex pathophysiology and requires treatment that includes long term administration of antipsychotics that is said to be associated with metabolic syndrome. This study was designed to evaluate the impact of seven different antipsychotics prescribed to schizophrenic patients, on development of metabolic syndrome in the patients. A total of 210 patients with schizophrenia (30 patients in each drug therapy group) were recruited according to ICD-10 criteria and were assigned to receive the drug for 16 weeks. Measurement of anthropometric (body weight, waist circumference, blood pressure) and biochemical parameters (glucose, insulin, HOMA-IR, triglycerides, LDL, HDL) was done and the patients were subjected to ATP-III defined criteria for metabolic syndrome. Patients undergoing treatment with olanzapine were more prone to metabolic syndrome as the drug induces weight gain after 16 weeks of treatment. It also induces dyslipidemia (P < 0.001) and hyperglycemia (P < 0.01). Clozapine was found to be second most potent drug in inducing metabolic syndrome as the weight in clozapine treated patients increased after 16 weeks, along with a significant increase in glycemic (P < 0.001) and lipid parameters (P < 0.01). Aripriazole and amisulphride are comparatively safer drugs as their role in inducing metabolic abnormalities in schizophrenic patients was insignificant, although the impact of long term administration of these drugs needs to be explored. It is clear from the study that antipsychotic treatment induces metabolic syndrome so, it becomes important that the metabolic and cardiovascular risk factors should be surveillance regularly in schizophrenic patients undergoing antipsychotic treatment.     

血浆纤维蛋白原水平升高同高血压,冠心病及卒中的联系

选择46岁以上的高血压(HBP)、冠心病(CHD)、卒中及其它内科住院病人共140名进行了血浆纤维蛋白原(FG)、血压、甘油三酯(TG)和吸烟等因素的观察.结果表明高血压、冠心病和车中患者FG值升高,逐步回归分析看出吸烟,HBP和TG水平升高明显影响FG的含量,提示FG水平升高同HBP,CHD和年中存在着紧密的联系。     

Effect of Resveratrol and Nicotine on PON1 Gene Expression: In Vitro Study

Dietary and lifestyle factors have been shown to have a profound effect on paraoxonase-1 (PON1) activity. Cigarette smoke has been shown to inhibit its mass and activity where as resveratrol has been shown to enhance it. We exposed hepatoma derived cell line (HepG2) to resveratrol and nicotine in varying doses and measured PON1 enzymatic activity and PON1 gene expression. In addition, total protein content of HepG2 cells was also measured. Resveratrol in a dose of 15 μmol/l or above significantly increased the PON1 enzyme activity (p > 0.001) where as nicotine in a dose of 1 μmol/l or higher significantly reduced it (p < 0.05). The resveratrol in this dose also enhanced the PON1 gene expression whereas nicotine decreased it as compared to controls. However, the protein conent of cells was not changed suggesting that they were not cytotoxic in the doses used. Till date the antioxidant vitamins have shown disappointing results against LDL oxidation and cardiovascular protection. However, the effect of resveratrol on PON1 gene expression and activity was significant, suggesting increase in PON1 activity and enhanced gene expression may be its alternative mechanism for offering protection against cardiovascular disease and may be an potential pharmacological agent which can be used for this.     

Protein Thiols and Butryrylcholinestrase in Saliva of Oral Cancer Patients

Oral squamous cell carcinoma is one of the most common malignancies recognized. Biomarkers which can predict presence of cancer and its progression can help in better management of these disorders. Over production of lipid peroxidation byproducts and disturbances in antioxidant defense system have been implicated in the pathogenesis of several diseases including oral cancer. Studies have shown a correlation of butyrylcholinesterase (BChE), with tumourigenesis, cell proliferation and cell differentiation. Earlier we have observed a significant elevation in plasma BChE and protein thiols in oral cancer patients which correlated well with stages of cancer. As it was not clear whether the above markers will be altered in saliva of oral cancer patients this study was undertaken. Institutional Ethics Committee gave permission to carry out this study. Total of 55 subjects comprising healthy controls (n = 30) and biopsy proven oral cancer patients (n = 25) consented to participate in this study. Salivary samples from cases were taken before any definitive treatment. Protein thiols and BChE were estimated in salivary samples using validated assay methods. Oral cancer patients had a significant increase in pre-treatment salivary BChE levels (p ≤ 0.001) and a significant decrease (p ≤ 0.001) in salivary thiols as compared to respective values in controls. Salivary protein thiols and BChE may have a role in pathophysiology of oral cancer. Saliva can be used as a potential non-invasive screening tool in oral cancer patients.