Modulation of CYP1A1, CYP1B1 and DNA adducts level by green and white tea in Balb/c mice.

In the current investigation the ameliorative effect of 2% extract of green tea (GT) and white tea (WT) against benzo(a)pyrene (BaP) induced toxicity and DNA damage has been studied in liver and lung of Balb/c mice (8 animals per group). The activities of phase I enzymes such as 7-ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-depentylase (PROD) were found to be increased (p<0.05) both in liver and lung of BaP treated (125 mg/kg b.w. orally) group. The enhanced activities of EROD and PROD were inhibited in group that received pretreatment with GT and WT for 35 days. Pretreatment with GT and WT also elevated (p<0.05) the level of detoxifying enzymes such as glutathione S-transferase (GST) and quinone reductase (QR) in both the tissues. The BaPDE-DNA adducts level reflected the decreasing pattern from BaP treated group to the groups that received pretreatment with GT and WT. BaP exposure induced drastic alterations in the morphology of erythrocytes, pretreatment of GT and WT to BaP administered groups showed reduced alteration in topography of erythrocytes. WT elucidate greater efficacy in ameliorating BaP toxicity, but further long term studies are required to validate white tea as a cancer chemopreventive agent.

Protective effects of green and white tea against benzo(a)pyrene induced oxidative stress and DNA damage in murine model.

In the current investigation, the ameliorative effect of green tea (GT) and white tea (WT) against benzo(a)pyrene (BaP) induced oxidative stress and DNA damage has been studied in the livers and lungs of Balb/c mice. A single dose of BaP (125 mg/kg, b.w. orally) increased the levels of lipid peroxidation (LPO) and decreased endogenous antioxidants such as superoxide dismutase (SOD), glutahione reductase (GR), catalase (CAT), and glutathione (GSH) significantly. Pretreatment with GT and WT for 35 days before a single dose of BaP elevated the decreased activity of GR, SOD, and CAT in liver tissue and also tended to normalize the levels of GSH and LPO in both hepatic and pulmonary tissues. The percentage of DNA in comet tail and 8-hydroxy-2'-deoxyguanosine levels reflected the decreasing pattern of DNA damage from the BaP-treated group to the groups that received pretreatment with GT and WT. Our study concludes that both GT and WT are effective in combating BaP induced oxidative insult and DNA damage. However, WT was found to be more protective than GT with respect to CAT (only in the liver), percentage of DNA in comet tail (only in the lungs), GST activity, and GSH content in both the tissues.

Selective estrogen receptor modulators regulate stromal proliferation in human benign prostatic hyperplasia by multiple beneficial mechanisms--action of two new agents.

The existing drugs for benign prostatic hyperplasia (BPH) are partially effective with undesirable side-effects; hence new agents acting by different mechanism(s) are required as supplements. Modulation of estrogen receptor signaling using selective estrogen receptor modulators (SERMs) offers an alternative approach for BPH management. Using human BPH-derived stromal cells and tissue explants in culture we evaluated two SERMs, DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2 H-1-benzopyran (BP) and Ormeloxifene (Orm) in comparison to Tamoxifen (Tam) and 4-hydroxytamoxifen (OHT). BP, OHT and Tam were more effective than Orm in reducing stromal cell proliferation of human BPH. BP was either equipotent or more effective than OHT and Tam in increasing estrogen receptor(ER)-ß, TGFß1, Fas and FasL, and in decreasing ER-α, AR, EGF-R and IGF-I expressions in BPH stromal cells. BP, Tam and Orm (1.0 mg/Kg) reduced rat prostate weights by almost same extent as Finasteride (Fin, 5.0 mg/Kg); however combination treatment (SERM+Fin) was more effective. BP was exceptionally efficient in reducing IGF-1 and cleaving PARP while combination treatments more effectively increased bax:bcl-2 ratio. Fin reduced acinar diameter and prostatic DHT level but increased testosterone, estradiol (E(2)) and E(2)/T+DHT ratio. SERMs, especially BP, reduced epithelial cell height drastically without significantly altering steroid hormone levels and E(2)/T+DHT ratio. Combination treatment reduced both acinar diameter and epithelial cell height with modest increase in E(2), T and E(2)/T+DHT. The study reveals the potential of SERMs per se for BPH management, and more effectively in combination with a 5α-reductase inhibitor. BP appears promising for further evaluation as a drug candidate for BPH and prostate cancer.