The effects of selenium supplementation on the spontaneously occurring fibroid tumors of oviduct, 8-hydroxy-2'-deoxyguanosine levels, and heat shock protein 70 response in Japanese quail.

Oxidative stress is known to be an important contributing factor in many chronic diseases. Spontaneously occurring benign oviduct leiomyomas are common tumors of the Japanese quail (Coturnix coturnix japonica), which makes it a good animal model for screening potential agents for testing in the prevention and treatment of human myoma uteri. Since dietary intake of selenium has been associated with a reduced risk of a variety of human cancers, we investigated the effects of selenium supplementation on the development of leiomyomas in the Japanese quail. Potential mechanisms of action of selenium include its antioxidant properties and modulation of heat shock protein 70 (Hsp70); therefore, we measured levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-isoprostane levels, and Hsp70 expression in tissue specimens obtained from the quails. One hundred and eighty quails (8 mo old) were assigned to 3 treatment groups consisting of 60 birds in each group. Birds were fed either a basal diet containing 0.048 mg Se per kg or the basal diet supplemented with 0.2 mg or 0.4 mg of selenium (Selenomax, yeast-bound l-selenomethionine, 60%) per kg of diet. The animals were sacrificed after 250 days, and the tumors were identified. Selenium supplementation did not affect the number of leiomyomas as compared to control subjects (P > 0.05). However, the tumors in selenium fed birds were smaller than those found in control birds (P = 0.01). Serum Se increased (P = 0.01), whereas MDA and 8-isoprostane, 8-OHdG concentrations decreased (P = 0.01) with selenium supplementation (P = 0.01). Selenium supplementation decreased Hsp70 in the tissue of birds. The results indicate that dietary supplementation with selenium reduces the size of spontaneously occurring leiomyoma of the oviduct in the Japanese quail.

Genistein suppresses spontaneous oviduct tumorigenesis in quail.

Spontaneous leiomyomas of the oviduct are common tumors of the Japanese quail (Coturnix coturnix japonica) and laying hens. This makes it a good animal model for screening potential agents for testing in the prevention and treatment of human myoma uteri. Genistein has been shown to inhibit the growth of various cancer cells. We investigated the effects of genistein supplementation on the development of fibroid tumors in the oviduct, serum oxidative stress markers [malondialdehyde (MDA), 8-isoprostane, 4-hydroxyalkenal (HAE), 8-hydroxy-2' -deoxyguanosine (8-OHdG) levels], soy isoflavone levels, and tissue biomarkers [Connexin 43 (Cx43), Bcl-2, and Bax and heat shock protein 70 (Hsp70) expression] in Japanese quail. One hundred and fifty quail (12 mo old) were assigned to 3 experimental groups as 5 replicates of pens containing 10 birds in each. Birds were fed either a basal diet or the basal diet supplemented with 400 mg or 800 mg of genistein/kg of diet. The animals were sacrificed after 315 days, and the tumors were identified. Genistein supplementation significantly decreased the incidence of fibroid tumors as compared to control birds (P = 0.04). The tumors in genistein-fed birds were smaller than those found in control birds (P = 0.02). Serum MDA, 8-isoprostane, and HAE levels were lower in treatment groups than in control group (MDA: 2.01 vs. 0.82; 8-isoprostane: 135 vs. 101; HAE: 1.45 vs. 0.73; P

Potential role of lycopene in the treatment of hepatitis C and prevention of hepatocellular carcinoma.

Hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) are growing health problems around the world. Oxidative stress plays a significant role in the initiation and progression of hepatocellular damage and possibly in the development of HCC in HCV infected patients. In vitro, animal and clinical studies suggest that lycopene, a nonprovitamin A carotenoid and a potent antioxidant, may attenuate the liver injury and possibly prevent the development of HCC. In this article, we discuss the relationship between HCV infection and oxidative stress and review the potential role of lycopene in the treatment of HCV and prevention of HCC.

Hepatic venous outflow obstruction: three similar syndromes.

Our goal is to provide a detailed review of veno-occlusive disease (VOD), Budd-Chiari syndrome (BCS), and congestive hepatopathy (CH), all of which results in hepatic venous outflow obstruction. This is the first article in which all three syndromes have been reviewed, enabling the reader to compare the characteristics of these disorders. The histological findings in VOD, BCS, and CH are almost identical: sinusoidal congestion and cell necrosis mostly in perivenular areas of hepatic acini which eventually leads to bridging fibrosis between adjacent central veins. Tender hepatomegaly with jaundice and ascites is common to all three conditions. However, the clinical presentation depends mostly on the extent and rapidity of the outflow obstruction. Although the etiology and treatment are completely different in VOD, BCS, and CH; the similarities in clinical manifestations and liver histology may suggest a common mechanism of hepatic injury and adaptation in response to increased sinusoidal pressure.

Chemoprevention of fibroid tumors by [-]-epigallocatechin-3-gallate in quail.

Spontaneous leiomyomas of the oviduct are common tumors of the Japanese quail (Coturnix coturnix japonica), and fibroid tumors in the laying hen are similar to human fibroid tumors with respect to estrogen and progesterone receptors. This makes the quail a good animal model for screening potential agents for that aid in the prevention and treatment of human myoma uteri. We have previously reported a decreased incidence of leiomyomas in the oviduct of Japanese quail with antioxidant supplementation, for example, lycopene and soy isoflavones. Most of the health benefits associated with green tea consumption is attributed to EGCG, one of 4 major catechins found in green tea. This study investigated the effects of epigallocatechin-3-gallate supplementation on the development of leiomyomas in the oviduct of Japanese quail. We also measured serum and tissue levels of malondialdehyde and TNF-alpha. One hundred eighty quail (8 months old) were assigned to 3 treatment groups consisting of 6 replicates of 10 quail in each group. Animals were fed either a basal diet (control group) or the basal diet supplemented with 200 or 400 mg of EGCG/kg of diet. The animals were euthanized at the end of the 12-month study period, and the tumors were characterized. Epigallocatechin gallate supplementation significantly decreased the number of leiomyomas as compared with the controls (P = .001). The tumors in the EGCG fed birds were smaller than those found in the control birds (P = .001). Serum and liver malondialdehyde and TNF-alpha concentrations decreased (P = .001) with EGCG supplementation. The results indicate that dietary supplementation with EGCG reduces the incidence and size of spontaneously occurring leiomyoma of the oviduct in Japanese quail. Clinical trials should be conducted to investigate the efficacy of EGCG supplementation in the prevention and treatment of uterine leiomyoma in humans.

Lycopene in cancer prevention and treatment.

Dietary intake of lycopene is inversely associated with the risk of many cancers. Preclinical studies show that lycopene has potent in vitro and in vivo antitumor effects, suggesting potential preventive and therapeutic roles for the compound. However, clinical trials with lycopene have only recently been started, and available clinical data preclude firm conclusions with regard to its use in cancer prevention and treatment. Further mechanistic studies and randomized controlled clinical intervention trials with lycopene involving cancer patients are warranted.

Dietary tomato powder supplementation in the prevention of leiomyoma of the oviduct in the Japanese quail.

Spontaneous leiomyomas of the oviduct are common tumors of the Japanese Quail (Coturnix coturnix japonica), which makes it a good animal model for screening potential agents for testing in the prevention and treatment of human myoma uteri. We have previously reported a decreased incidence of leiomyomas in the oviduct of Japanese quail with lycopene supplementation. Although the major carotenoid in tomatoes is lycopene, tomatoes also contain other compounds, which may contribute to their health benefit. Therefore, in this study, we investigated the effects of tomato powder supplementation on the development of leiomyomas in the oviduct of Japanese quail. We also measured serum levels of malondialdehyde (MDA), carotenoids, and vitamins C, E, and A. A total of 150 quails (3 mo old) were assigned to 3 treatment groups consisting of 5 replicates of 10 birds in each group. Birds were fed either a basal diet (control group) or the basal diet supplemented with 25 g (Treatment I) or 50 g (Treatment II) of tomato powder (0.8 mg lycopene per g of tomato powder) per kg of diet. The animals were sacrificed after 365 days, and the tumors were identified. Tomato powder supplementation significantly decreased the number of leiomyomas as compared to control birds (P < 0.01). The tumors in tomato powder fed birds were smaller than those found in control birds (P < 0.01). Serum lycopene, lutein, zeaxantin, and vitamins C, E, and A increased (P = 0.01), whereas MDA concentrations decreased (P = 0.01) with tomato powder supplementation. No measurable lycopene could be detected in the serum of control birds, whereas a dose-dependent increase was observed in the serum of birds supplemented with tomato powder. The results indicate that dietary supplementation with tomato powder reduces the incidence and size of spontaneously occurring leiomyoma of the oviduct in the Japanese quail. Clinical trials should be conducted to investigate the efficacy of tomato powder supplementation in the prevention and treatment of uterine leiomyoma in humans.

Lycopene and soy isoflavones in the treatment of prostate cancer.

Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines. In a previous Phase II clinical trial in prostate cancer patients, we observed prostate-specific antigen (PSA) stabilization with soy isoflavone intake. In this Phase II clinical trial, we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer. To be eligible for the study, men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy. Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33) twice daily orally for a maximum of 6 mo. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill. There was no decline in serum PSA in either group qualifying for a partial or complete response. However, 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer. However, there may not be an additive effect between the 2 compounds when taken together. Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them.