CHEMOTHERAPEUTIC EFFICACY OF TRIDHAM AND 1,2,3,4,6-PENTA-O-GALLOYL-β-DGLUCOSE ON ANTIOXIDANTS STATUS AND TUMOR MARKERS IN EXPERIMENTAL MAMMARY CARCINOMA IN SPRAGUE-DAWLEY RATS

Objective: 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

EFFICACY OF TRIDHAM AND 1,2,3,4,6-PENTA-O-GALLOYL-β-D-GLUCOSE IN REVERSING LIPID PEROXIDATION LEVELS AND MITOCHONDRIAL ANTIOXIDANT STATUS IN 7,12-DIMETHYLBENZENEANTHRACENE (DMBA) INDUCED BREAST CANCER IN SPRAGUE-DAWLEY RATS

Objective: To determine the effect of Tridham (TD) and 1,2,3,4,6-penta-O-galloyl-β-d-glucose(PGG) on lipid peroxidation levels and mitochondrial antioxidants status in experimental mammary carcinoma.Methods: Elaecoarpus ganitrus (fruits), Terminalia chebula (seed coats), Prosopis cineraria (leaves), adult female albino rats of Sprague-Dawley strain weighing 170–190 g and 7,12-dimethylbenzeneanthracene (DMBA) were used for this study. Group I control rats, Group II rats mammary carcinoma induced with DMBA (25 mg in 1 ml olive oil) by gastric intubation. Group III, IV and V DMBA induced rats were treated with TD (400 mg/kg. b. wt/day), PGG (30 mg/kg. b. wt/day) and standard drug, Cyclophosphamide (30 mg/kg. b. wt/day), respectively for 48 d by gastric intubation. Group VI and VII rats served as TD and PGG treated controls, respectively for 48 d by gastric intubation. At the end of the experimental period, the rats were anaesthetized and sacrificed. Mammary glands were isolated and used for biochemical assays and histopathological evaluation.Results: In rats with cancer, the lipid peroxide levels (LPO) were significantly increased and mitochondrial antioxidant levels were decreased. Treatment with TD and PGG decreased LPO levels and increased mitochondrial antioxidant status in mammary carcinoma bearing rats. Histopathological analysis also confirmed the therapeutic effect of TD and PGG. No significant adverse effect was observed in sole drug treated group of rats.Conclusion: TD and PGG have definite therapeutic effect in experimental mammary carcinoma and inhibit growth of cancer cells by restoring mitochondrial antioxidant status and energy metabolism to normal states

THERAPEUTIC EFFECT OF TRIDHAM AND 1,2,3,4,6-PENTA-O-GALLOYL-Î’-D-GLUCOSE ON ALTERED ENERGY METABOLISM IN MAMMARY CARCINOMA BEARING RATS

ABSTRACTObjective: Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production, and hence,reprogramming of cellular energy metabolism is deemed to be one of the principal hallmarks of cancer. Tridham (TD) has been used by traditionalpractitioners of Siddha medicine against various ailments. Hence, the present study has been designed to evaluate the therapeutic effect of TD onaltered energy metabolism in mammary carcinoma-bearing rats.Methods: Adult female albino rats of Sprague-Dawley strain weighing 170-190 g were used and 7,12-dimethylbenzeneanthracene (DMBA) was used forinduction of mammary carcinoma and rats were divided into seven groups. Group I - control rats, Group II - DMBA-induced rats, Group III - DMBA- andTD-treated rats, Group IV - DMBA- and 1,2,3,4,6-Penta-O-galloyl-β-d-glucose (PGG)-treated rats, Group V - DMBA- and cyclophosphamide-treated rats,Groups VI and VII are TD and PGG control rats.Results: Significant (p<0.05) increase in the glycolytic enzymes, hexokinase, phosphoglucoisomerase and aldolase, was observed in tumor-bearingrats whereas gluconeogenic enzymes, glucose-6-phosphatase and fructose-1,6-biphosphatase, were significantly decreased. The activities of themitochondrial Krebs cycle enzymes, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase,and respiratory chain enzymes, nicotinamide dinucleotide dehydrogenase and cytochrome c oxidase, were significantly reduced in tumor tissue ofthe mammary carcinoma-bearing rats. These biochemical disturbances were effectively counteracted by TD and PGG which restore the activities of allthese enzymes to the respective control levels.Conclusion: TD and PGG effectively ameliorated the altered glucose metabolism resulting in the regression of breast cancer.Keywords: Breast cancer, Cancer cachexia, Carbohydrate-metabolizing enzymes, Krebs cycle

MITOCHONDRIA : AS A PROTAGONIST IN NEUROLOGICAL DISORDERS IN BRIEF OVERVIEW: Role of mitochondria in neurological disorders

Neurological disorders pose a great burden in general health. It is not astounding that mitochondrial malfunction emerging as a leading factor in myriad of neurological disorders. Mitochondria are extremely active cell organelles performing various functions most importantly, providing ATP to sustain cellular processes. Mitochondrial dysfunction results in altered neuronal bioenergetics, redox equilibrium and dynamics of cell and acts as focal point of pathogenesis in many human diseases including neurological disorders. Mitochondrial dynamics regulates pathways involving oxidative stress and apoptosis. Often mitochondrial division imbalance and fusion leads to mitochondrial functional impairment. Extreme variations in mitochondrial fusion causes increased mutation rate which along with increased oxidative stress can facilitate development of various neurological disorders such as Parkinson’s disease, Alzheimer’s disease, Huntington’s diseases and so on. Mitochondria has a key role in regulation of apoptosis. Mitochondrial dysfunction and mutations can have deleterious effects on neuronal functioning as neurons have high energy demand with restricted regenerative potential. Certain neuroprotective agents restores the functions of mitochondria and acts therapeutic regimens of neurodegenerative diseases