Chemopreventive and therapeutic modulation of green tea polyphenols on drug metabolizing enzymes in 4-Nitroquinoline 1-oxide induced oral cancer.

Oral cancer is one of the most common cancers in the world. Drugs can modulate the expression of drug metabolizing enzymes and are useful in chemoprevention as well as therapy in cancer. 4-Nitroquinoline 1-oxide (4-NQO) is used to induce oral cancer in the present study. In the present investigation, the effect of green tea polyphenols (GTP) on the activities of cytochrome b5, cytochrome P450, cytochrome b5 reductase (cyt b5 R), cytochrome P450 reductase (cyt P450 R), arryl hydrocarbon hydroxylase (AHH), DT-diaphorase (DTD)(Phase I enzymes) and glutathione-S-transferase (GST) and UDP-glucuronyl transferase (UDP-GT) (Phase II enzymes) were assessed in tongue and oral cavity. In induced rats, there was a decrease in the activity of Phase II enzymes and an increase in the activity of Phase I enzymes. On supplementation of GTP by both simultaneous and post treatment mode (200mg/kg) there was a significant increase in the activity of GST and UDP-GT and a significant decrease in the activity of Phase I enzymes. There was a significant decline in the number of tumors, tumor volume and oral squamous cell carcinoma in both simultaneous and post GTP treated animals relative to 4-NQO induced animals; on comparing simultaneous and post GTP treated animals the number of tumors, tumor volume and oral squamous cell carcinoma was significantly reduced in post treated animals. Thus inhibition of Phase I enzymes could be attributed to the protective efficacy of GTP which deactivates carcinogen and GTP induced the expression of Phase II enzymes that detoxifies the 4-NQO. It can be proposed that GTP plays role as a detoxifying agent by which its modulating role prevented/inhibited the formation of tumor.

Effect of T. chebula on mitochondrial alterations in experimental myocardial injury.

Mitochondria play a central role in molecular events leading to tissue damage in ischemia. The present study examines the role of the alcoholic extract of T. chebula (TCE) pretreatment (50 mg/100 g body weight) to attenuate the isoproterenol (ISO) (20mg/100g body wt, sc) induced alterations on heart mitochondrial ultrastucture and function in experimental rats. ISO induced cardiotoxicity was evidenced by a significant rise in the level of lactate, decrease in enzyme activities of tricarboxylic acid cycle (TCA), mitochondrial respiration, levels of adenosine triphosphate (ATP) and oxidative phosphorylation. TCE intervention significantly attenuated the above alterations by ISO and retained near normal function of the mitochondria. Electron microscopic studies of the mitochondria further support the isoproterenol induced deleterious changes and accredit the protective effect of TCE on mitochondrial structure and energy metabolism.

Antioxidant activity of ethanolic extract of Terminalia chebula fruit against isoproterenol-induced oxidative stress in rats.

Antioxidant activity of ethanolic extract of fruits of Terminalia chebula (500 mg/kg body wt, orally for 30 days) against isoproterenol-induced oxidative stress was investigated in rats. The levels of serum lipid peroxides, iron, ascorbic acid, vitamin E, plasma iron-binding capacity, and the activities of ceruloplasmin and glutathione were assayed, in addition to the activities of the antioxidant enzymes--glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase in the heart tissue. Administration of isoproterenol increased the levels of lipid peroxides and iron, with corresponding decrease in the activities of the enzymic and non-enzymic antioxidants. The pre-treatment with ethanolic extract of fruits significantly prevented the alterations induced by isoproterenol, and maintained a near normal antioxidant status. Results suggest that the cardioprotective effect of T. chebula fruit may partly be attributed to its antioxidant properties.

Protective effect of Terminalia chebula against lysosomal enzyme alterations in isoproterenol-induced cardiac damage in rats.

BACKGROUND: Terminalia chebula is an ayurvedic drug recommended for the treatment of heart diseases. Earlier studies by the authors validated the beneficial cardioprotective effect of T chebula against isoproterenol-induced myocardial infarction. OBJECTIVES: To evaluate the therapeutic efficacy of T chebula in protecting against isoproterenol-induced lysosomal membrane damage. METHODS: Lysosomal enzyme activities from the serum, heart and lysosomal fractions were determined. The triphenyltetrazolium chloride assay was used to confirm the protective effect of T chebula on the myocardium. RESULTS: Isoproterenol administration produced significant cardiac damage (as seen by the triphenyltetrazolium chloride assay) and significantly altered lysosomal enzyme activities. Pretreatment with an ethanol extract of T chebula was found to retain near normal activities of lysosomal enzymes in rats given T chebula or T chebula plus isoproterenol compared with rats given isoproterenol alone. CONCLUSIONS: Pretreatment with T chebula extract stabilizes the lysosomal membrane and, thus, may have prevented myocardial damage.