Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins

OBJECTIVES: Tamoxifen (TAM), a non-steroidal anti-estrogen that is widely used in adjuvant therapy for all stages of breast carcinomas and in chemoprevention of high-risk group. The hepatic estrogenic effect of TAM induces hypertriglyceridemia by reduced activity of lipolytic enzymes (LPL) on triglycerides. Coenzyme Q10 (Co Q10), riboflavin and niacin are proved to be potent antioxidant and protective agents against many diseases including cancer and cardiovascular diseases (CVD). In this context, the objective of the study is to find the effect of the combined modality of Co Q10 (100 mg), riboflavin (10 mg) and niacin (50 mg) with TAM (10 mg twice a day) on serum lipids and lipoprotein levels in postmenopausal women with breast cancer. DESIGN AND METHODS: The vitamin supplementation with tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma total cholesterol (TC), free cholesterol (FC), ester cholesterol (EC), phospholipids (PL), triglycerides (TGL), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low density cholesterol (VLDL-C) were estimated in 78 untreated, only TAM-treated and combinatorialy treated group along with 46 age- and sex-matched controls. RESULTS: Serum TGL and VLDL-C (p<0.001) were found to be significantly elevated and LDL-C (p<0.01), significantly reduced among TAM-treated patients as compared to the untreated breast cancer subjects. All the lipids and lipoprotein levels were found to be significantly altered in the untreated breast cancer patients when compared to their normal counterparts. All the lipid and lipoprotein abnormalities were reverted back to near normal levels on 90 days of treatment on combinatorial therapy. CONCLUSION: The study figures the altered lipid and lipoprotein levels in the untreated and TAM-treated breast cancer patients. On combination therapy with Co Q10, riboflavin and niacin, it counteracts the tamoxifen-induced hyperlipidemia to normal levels.     

Anihypercholesterolemic effect of Semecarpus anacardium Linn nut milk extract in high-cholesterol-fed rats

The present study was carried to bring about the hypolipidemic effect of the drug Semecarpus anacardium Linn nut milk extract (SA) in hypercholesterolemia-induced rat model. Adult male Wistar rats were divided into four groups which included control rats, hypercholesterolemia-induced rats (high-cholesterol diet (4 %) for 30 days), hypercholesterolemic rats treated with the drug SA (200 mg/kg/b. wt oil), and the control rats treated with the drug SA (200 mg/kg/b. wt). Increased level of ROS and lipid peroxides were observed in hypercholesterolemic rats, whereas the levels of activities of antioxidant enzymes were found to be decreased in animals fed with a high-fat diet. Simultaneous administration of SA to these rats reverted back the changes to near-normal levels. Similarly, an increase in the expression of iNOS and LOX-1 were observed in high-fat-fed rats when compared to normal rats. Upon treatment with the drug SA, their expressions were brought back to near-normal levels. No adverse effects were observed in SA-alone treated group of rats, indicating its protective nature. The present study suggests that SA could play a protective role against hypercholesterolemia, thereby preventing coronary heart disease.     

Immunomodulatory effect of Kalpaamruthaa on 7,12-dimethyl benz(a)anthracene-induced mammary carcinoma studied in rats

Kapaamruthaa is a modified Siddha preparation prepared in our laboratory. It has been proven to have therapeutic effect against arthritis and liver cancer. The present study was carried out to bring about the protective effect of Kalpaamruthaa on experimental mammary carcinoma in rats with special reference to cytokines, carcinoembryonic antigen (CEA), carbohydrate antigen 15–3 (CA 15–3), immunoglobulin levels, and glycoprotein components. Breast cancer was induced in rats by administering 7,12-dimethylbenz(a)anthracene (DMBA) orally (25 mg/rat) as a single dose. After 90 days of induction, Semecarpus anacardium Linn. (200 mg/kg body weight) and Kalpaamruthaa (KA) (300 mg/kg body weight) were administered for 14 days, by gastric intubation. In mammary carcinoma-bearing rats, the levels of interleukin-6, interleukin-8, and tumor necrosis factor-α were significantly increased (p?<?0.001) in serum when compared to control rats. The levels of CEA and CA 15–3 were found to be significantly increased (p?<?0.001) in mammary carcinoma-bearing rats. The levels of IgG and IgM were significantly decreased (p?<?0.001) whereas IgA levels were significantly increased (p?<?0.001) in mammary carcinoma-bearing rats. The levels of glycoprotein components namely hexose, hexosamine, and sialic acid were significantly (p?<?0.001) increased in the spleen and thymus of the mammary carcinoma-bearing (group II) rats when compared to control rats. Treatment with KA significantly altered the levels of cytokines, CEA, CA 15–3, immunoglobulins, and glycoprotein components to near normal levels when compared to breast cancer-induced rats. The present study suggests the therapeutic effect of KA in DMBA-induced mammary carcinoma in rats.     

Recuperative effect of Semecarpus anacardium linn. nut milk extract on carbohydrate metabolizing enzymes in experimental mammary carcinoma-bearing rats

Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. We have tested the antitumour activity of Semecarpus anacardium nut extract against experimental mammary carcinoma in animals. As there is a direct relationship between the proliferation of tumour cells and the activities of the glycolytic and gluconeogenic enzymes, we studied changes in the activities of enzymes involved in this metabolic pathway in the liver and kidney. The enzymes investigated were glycolytic enzymes, namely hexokinase, phosphoglucoisomerase, aldolase and the gluconeogenic enzymes, namely glucose-6-phosphatase and fructose-1,6-biphosphatase in experimental rats. A significant rise in glycolytic enzyme activities and a simultaneous fall in gluconeogenic enzyme activities were found in mammary carcinoma bearing rats. Drug administration returned these enzyme activities to their respective control activities.     

Effect of Semecarpus anacardium nut extract on ECM and proteases in mammary carcinoma rats

The early stages of invasion are characterized by the extracellular proteolysis and the accumulation of specialized extracellular matrix (ECM) scaffold, that are responsible for the development of vascular bed, endothelial cell proliferation and invasion of tumour cells. The ground substance of provisional matrix consists of collagen, elastin, glycoaminoglycans and proteoglycans that facilitate the interaction of tumour cells with the host environment. In the present work, we have studied the influence of Semecarpus anacardium nut milk extract on localized differentials of ECM component and proteases involved in matrix metabolism of tumour tissue. Mammary carcinoma was induced in Sprague Dawley rats with 7,12, dimethyl benz(a)anthracene and treated with S. anacardium nut milk extract administered orally for 14 days. The altered amount of ECM components in tumour tissues was almost reverted back to normal level in the drug treated animals. The activities of reported proteases and glycohydrolases were also decreased on treatment with S. anacardium nut milk extract indicating decreased turnover of the matrix. Also, the factors associated with the matrix turnover and expression of MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-2 were restored back to near normal values. The stabilization of the ECM with the decreased activity of proteases might inhibit the epithelial-endothelial interaction and tumour cell migration thus, preventing the adjacent invasion and tumour growth and might be regarded as antineoplastic agent which demands further studies.     

Phytochemical analysis and anticancer capacity of Shemamruthaa,a herbal formulation against DMBA- induced mammary carcinoma in rats

ObjectiveTo investigate the bioactive constituents of Shemamruthaa (SM), a herbal combination and its therapeutic effects on the mitochondrial functions with reference to lipid peroxidation (LPO), antioxidant status, citric acid cycle enzymes and electron transport chain enzymes in mammary tissues of 7,12-dimethylbenz(a)-anthracene (DMBA) induced mammary carcinoma in rat model.MethodsAdult female Sprague-Dawley rats were used for the study and were divided into four groups. Group I served as control and Group II rats were induced mammary carcinoma by administration of DMBA (25 mg/kg b.w.) orally. The normal and cancer-induced rats (Group III) were treated with SM (400 mg/kg b.w./day) orally by gastric incubation for 14 days. Group IV rats served as SM-treated control animals.ResultsCancer-induced rats showed a considerably increased level of LPO with concomitant decreased levels of antioxidants, citric acid cycle enzymes, electron transport chain enzymes and cytochrome contents in the mammary tissue. Treatment with SM brought back the aforementioned biochemical parameters to near normal.ConclusionsFrom the results, it can be inferred that Shemamruthaa possesses significant anticancer effect through its role in attenuation of LPO, prevention of membrane damage and restoring membrane integrity.     

Therapeutic effect of tamoxifen and energy-modulating vitamins on carbohydrate-metabolizing enzymes in breast cancer

Background Cancer cells have an abnormal energetic metabolism. One of the earliest discovered hallmarks of cancer had its roots in bioenergetics, as many tumours were found in the 1920s to exhibit a high glycolytic phenotype. An animal with cancer shows significant and progressive energy loss from the host (i.e. noncancerous) tissues, which could occur by the establishment of a systemic energy-depriving cycle involving the interaction of tumour glycolysis and host gluconeogenesis. Tamoxifen (TAM) is a nonsteroidal antioestrogen that is widely used in adjuvant therapy for all stages of breast carcinoma. To improve the therapeutic efficacy of TAM and to expand its usage in the treatment of breast cancer, it is necessary to establish an energy-enhancing programme. In order to provide sufficient energy and to prevent cancer cachexia, TAM can be supplemented with energy-modulating vitamins (EMV). In this investigation the augmentation of the efficacy of TAM by the effects of EMV supplementation on carbohydrate-metabolizing enzymes, the mitochondrial Krebs cycle and respiratory enzymes was evaluated in the mammary gland of carcinoma-bearing rats.Methods Female albino Sprague-Dawley rats were selected for the investigation. The experimental set-up included one control and four experimental groups. Mammary carcinoma was induced with 7,12- dimethyl benz(a)anthracene (25 mg), and TAM was administered orally (10 mg/kg body weight per day) along with EMV which comprised riboflavin (45 mg/kg per day), niacin (100 mg/kg per day) and coenzyme Q₁₀ (40 mg/kg per day).Results Measurements were made on tumour tissue and surrounding normal tissue in all experimental groups. Tumour tissue showed significant (P<0.05) increases in the glycolytic enzymes hexokinase, phosphoglucoisomerase and aldolase, and significant decreases in the gluconeogenic enzymes glucose-6-phosphatase and fructose-1,6-biphosphatase. In contrast, the surrounding tissue showed significant decreases in glycolytic enzymes and significant increases in gluconeogenic enzymes. The activities of the mitochondrial Krebs cycle enzymes isocitrate dehydrogenase, -ketoglutarate dehydrogenase, succinate dehydrogenase and malate dehydrogenase, and respiratory chain enzymes NADH dehydrogenase and cytochrome c oxidase were significantly reduced in both tumour and surrounding tissue of the mammary carcinoma-bearing rats. These biochemical disturbances were effectively counteracted by supplementation with EMV, which restored the activities of all these enzyme to their respective control levels.Conclusion Combination therapy of TAM with EMV not only alters carbohydrate metabolism but can also prevent body weight loss by enhancing the host energy metabolism.     

Effect of Semecarpus anacardium Linn. nut extract on mammary and hepatic expression of xenobiotic enzymes in DMBA-induced mammary carcinoma

Breast cancer is the major cause of cancer death in women worldwide. Environmental risk factors particularly genotoxic chemicals such as polycyclic aromatic hydrocarbons (PAH) are likely to account for a much higher mortality. Xenobiotic metabolising enzymes in breast tissue are potentially important determinants in both the susceptibility to the mutagenic effects of chemical carcinogens and in the response of breast tumors to chemotherapy. The well known carcinogen 7,12-dimethylbenz(a)anthrazene of PAH family was given (25 mg/ml) orally by gastric intubation to induce mammary carcinoma in Sprague-Dawley rats. Increased level of cytochromes (P₄₅₀, B₅), EROD, PROD activities, Phase I biotransformation enzymes (NADPH-cytochrome (P₄₅₀) reductase, NADPH-cytochrome (b₅) reductase, epoxide hydrolase) and expression of CYP1A1, CYP1A2 and CYP1B1 in liver and breast tissue microsome were documented in DMBA treated group. Phase II enzyme activities (glutathione-S-transferase, gluthatione peroxidase, gluatathione reductase, UDP-glucuronyl transferease) were decreased markedly in cancerous rats. The nut extract of Semecarpus anacardium was administered orally (200 mg/kg body wt/day) to the mammary carcinoma rats for 14 days. Drug treatment restored back the altered Phase I and II biotransformation enzymes thus achieving complete detoxification of the carcinogen. These findings suggest that S. anacardium can effectively modulate the catabolism of xenobiotics in rats.     

Anti-inflammatory and anti-hyperlipidemic effect of Semecarpus anacardium in a High fat diet: STZ-induced Type 2 diabetic rat model

Introduction

Semecarpus anacardium, known as marking nut, has been used in indigenous system of medicine against various ailments.

Aim

To evaluate the antilipidemic and anti-inflammatory effect of S. anacardium Linn. nut milk extract (SA) in Type 2 diabetic rats.

Materials and methods

Diabetes was induced in rats by feeding them with a high fat diet followed by i.p. of 35 mg/kg body weight of streptozotocin. Diabetic rats were treated with the drugs, SA (200 mg/kg body weight) and metformin (500 mg/kg body weight) for 30 days. Antilipidemic effect of the drug was established by studying the lipoprotein alterations and also the alterations in the lipid profile and lipid metabolizing enzymes in the experimental group of rats. The effect of the drug on the expression of PPAR γ was also studied. To determine the anti-inflammatory effect of the drug, the levels of inflammatory cytokines, TNF-α and IL-6 and also C-reactive protein were determined.

Results and discussion

Semecarpus anacardium nut milk extract at a dosage of 200 mg/kg orally significantly (p < 0.05) reduced and normalized the alterations in the lipid metabolism in diabetic rats effectively than metformin. SA treatment significantly (p < 0.05) increased the mRNA expression of PPAR γ, thereby establishing the antilipidemic effect of the drug. The increase in the levels of inflammatory cytokines were significantly (p < 0.05) brought down to near normal levels on treatment with the drug SA.

Conclusion

The present study thereby establishes the antilipidemic and anti-inflammatory effect of the drug. Thus, by decreasing the alterations in the lipid metabolism and inflammatory status, the drug can effectively improve the insulin sensitivity in rats and can serve as an excellent drug in the treatment of Type 2 diabetes mellitus.