A review of metallothionein isoforms and their role in pathophysiology.

The Metallothionein (MT) is a protein which has several interesting biological effects and has been demonstrated increase focus on the role of MT in various biological systems in the past three decades. The studies on the role of MT were limited with few areas like apoptosis and antioxidants in selected organs even fifty years after its discovery. Now acknowledge the exploration of various isoforms of MT such as MT-I, MT-II, MT-III and MT-IV and other isoforms in various biological systems.Strong evidence exists that MT modulates complex diseases and the immune system in the body but the primary function of MT still remains unknown. This review's main objective is to explore the capability to specifically manipulate MT levels in cells and in animals to provide answers regarding how MT could impact those complex disease scenarios.The experimental result mentioned in this review related among MT, zinc, cadmium, diabetic, heart disease, bone retardation, neuro toxicity, kidney dysfunction, cancer, and brain suggest novel method for exploration and contribute significantly to the growing scientist to research further in this field.

Metallothionein: an overview.

Metallothioneins (MTs) were discovered in 1957 by Margoshes and Vallee and identified as low-molecular weight and sulphydryl rich proteins. It is not surprising that most mammalian tissues contain age related basal levels of MTs since they are involved in metalloregulatory processes that include cell growth and multiplication. In an effort to understand the biology of this intriguing tumor, various biomarkers such as oncogenes, p53 tumor suppressor gene, waf 1 protein, proliferating cell nuclear antigen, telomerase, microsatellite markers and cytogenetic changes have been examined. One biomarker which has recently shown to be expressed in various human tumors but still less reported in carcinoma is MT. Immunohistochemical detection of MT proteins in cold acetone-fixed paraffin embedded liver sections was performed by the streptavidin-avidin-biotin immuno-peroxidase complex method.

Vanadium induces apoptosis and modulates the expressions of metallothionein, Ki-67 nuclear antigen, and p53 during 2-acetylaminofluorene-induced rat liver preneoplasia.

Our previous studies have shown that vanadium, a dietary micronutrient, has an inhibitory effect against experimentally induced rat hepatocarcinogenesis. In this study, we evaluated the role of vanadium on some potential protein expression markers of carcinogenesis, such as metallothionein (MT), an intracellular metal-binding protein linked with cell proliferation and apoptosis, Ki-67 nuclear antigen, and p53 tumor suppressor during 2-acetylaminofluorene (2-AAF)-induced (0.05% in basal diet) rat liver preneoplasia. In a short-term regimen, supplementation of vanadium at a dose of 0.5 ppm effectively suppressed the formation of DNA 'comets' (29.55%; P < 0.02), thereby indicating its nongenotoxicity at this particular dose. Vanadium administration throughout the study reduced relative liver weight (RLW), nodular incidence (57.15%), total number, and multiplicity (48.45%) with restoration of hepatic zinc (Zn), magnesium (Mg), selenium (Se), copper (Cu), iron (Fe), and calcium (Ca) contents when compared to the carcinogen control. Moreover, treatment with vanadium significantly abated the expressions of MT and Ki-67, studied at four sequential time points. An increased immunopositivity of p53 protein (1.03 +/- 0.23%; P < 0.02) was found in vanadium-treated rat liver with an elevated apoptotic-labeling index (AI; P < 0.001) as documented by TUNEL assay. Furthermore, a positive correlation between MT expression and Ki-67 labeling along with a strong negative correlation between MT immunoreactivity and AI (r = -0.9000, P = 0.0004 at week 24) at various time intervals suggest that, vanadium-mediated suppression of MT and Ki-67 expressions may be associated with induction of apoptosis. The results thus provide evidence for the first time in support of the potential role of vanadium on induction of p53 and apoptosis with concurrent suppression of MT and Ki-67 in order to have an understanding, in part, of the chemopreventive mechanism of this trace element in limiting neoplastic transformation in a defined model of experimental rat hepatocarcinogenesis.

Spectrophotometric analysis of raloxifene hydrochloride in pure and pharmaceutical formulations.

Two simple and sensitive spectrophotometric methods (A and B) for the determination of raloxifene hydrochloride in bulk samples and pharmaceutical formulations are described. Method A is based on the oxidation of the drug with ferric chloride and coupling with potassium ferric cyanide. Method B is based on reduction of the drug with Fehling's reagent. Bluish green color formed in method A absorbs at 735 nm and brown color produced in method B absorbs at 430 nm.