Tamoxifen is the commonly used adjuvant therapy for all stages of breast carcinoma. However, several studies have suggested an association between the use of tamoxifen in breast cancer patients and the subsequent development of endometrial carcinoma. Riboflavin, niacin and ascorbic acid are proved to be potent antioxidants and protective agents against many diseases including cancer. The objective of this article is to determine the curative effect of riboflavin, niacin and ascorbic acid on tamoxifen mediated endometrial carcinoma bearing rats in terms of lipid peroxidation and antioxidant status. In endometrial carcinoma bearing rats, levels of lipid peroxides were increased and the activities of enzymic and non-enzymic antioxidants were decreased. Oral administration of drug for 28 days restored lipid peroxide level and the activities of enzymic and non-enzymic antioxidants to near normal levels.
The quantitation of myocardial reperfusion injury in patients often creates problems due to lack of specific markers. Although malondialdehyde provides an index of oxidative damage, we have little information regarding effects on membrane structure and function. Therefore we investigated the effect of ischemia/reperfusion on the kinetics of protein modification along with lipid peroxidation during coronary angioplasty. Venous blood samples were collected before angioplasty and at various intervals after primary stage of balloon deflation from humans to quantitate the above parameters. A significant transient rise in the concentration of protein carbonyls in serum (p<0.001) was observed soon after successful reperfusion which parallels with that of lipid peroxides. This increase of protein carbonyls is an actual reflection of the increased rate of amino acid modification in membrane proteins. These structural modifications can alter lipid-protein interactions resulting in disturbed membrane functions. This study suggests that protein modification and lipid peroxidation play significant role in the pathogenesis of myocardial reperfusion injury. Further this assessment of structural modification in proteins provides an important reliable technique to detect and quantitate the exact nature and extent of myocardial injury.
The regulation of adipose tissue distribution is an important problem in view of the close epidemiological and metabolic associations between centralized fat accumulation and disease. However, the majority of studies concerning adipose tissue distribution and metabolic disorders have focused on subjects already being obese. In this study, the effects of a high-carbohydrate diet (CHO) and a high-fat diet (FAT) on mass and function of mesenteric adipose depot, drained by the mesenteric vein, was examined in the pre-obese rat model. After 4 weeks of iso-energy feeding, the ratio of mesenteric adipose tissue weight to non-mesenteric was significantly greater in the CHO-fed group than in the FAT-fed group. Incorporation of orally administrated 3H-glucose into the mesenteric depot was more rapid in the CHO-fed group than in the FAT-fed group, but its incorporation into the non-mesenteric depot was similar between the two dietary groups. Arterial and mesenteric concentrations of free fatty acid and triglyceride of the CHO-fed group were significantly higher than those of the FAT-fed group. Gene expression of PPAR-γ and UCP-2 was similar among adipose depots, and there was no significant difference between the two dietary groups. In conclusion, dietary carbohydrate was preferentially incorporated into the total lipid in mesenteric adipose tissue. Without an increase in total body fat, CHO feeding for 4 weeks reinforces incorporation of dietary glucose into mesenteric depot, resulting in an increases of relative mesenteric adipose mass and portal FFA delivery.
The hypotheses that nitrotyrosine formation is a downstream mechanism following TNF-α production in lipopolysaccharide (LPS)-induced liver injury and its inhibition reduces the injury were examined. Under anesthesia, experiments were performed 6h after the intravenous administration of LPS (10mg/kg) or saline using male Sprague-Dawley rats (300-400g). Liver injury was evaluated in 4 groups: control (n=4), LPS alone (n=5), LPS+quercetin (n=5), LPS+clodronate (n=5) by plasma alanine aminotransferase (ALT) level, nitrotyrosine concentration in liver and histological changes. Quercetin, an inhibitor of nitrotyrosine formation was injected at a dose of 50mg/kg i.p. 24h before the LPS injection and clodronate, a Kupffer cell remover was injected i.v. at a dose of 0.2ml (0.23M) 24h before the LPS injection. Nitrotyrosine was measured by enzyme-linked immunosorbent assay and high performance liquid chromatography-electrochemical detection methods. In the LPS group, the liver contained 1, 403±240ng nitrotyrosine/g protein (control: 21.2±1.7ng/g) and plasma ALT was elevated (1, 781±455IU/liter vs. control 55±5IU/liter). Nitrotyrosine formation was decreased in the LPS+quercetin and LPS+clodronate groups (240.6±47.6 and 301.4±26.2ng/g protein, respectively) and the increase of plasma ALT was attenuated (486±20.7 and 79.8±9.4IU/liter, respectively). The plasma TNF-α level was markedly elevated in the LPS group (1, 124.1±67.6pg/ml). It remained high in quercetin groups (1, 292.4±159.9pg/ml) but was very low in the clodronate group (34.8±5.3pg/ml). LPS-induced liver injury involves nitrotyrosine formation and treatments to decrease its formation attenuated the injury. The protection was observed without affecting TNF-α level; suggesting that the nitrotyrosine formation is a downstream mechanism for the injury following TNF-α production.