Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

INTRODUCTION: Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. OBJECTIVE: The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. DESIGN AND METHODS: The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. RESULTS: LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. CONCLUSIONS: In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours.

Androgen receptor expression in human thyroid cancer tissues: a potential mechanism underlying the gender bias in the incidence of thyroid cancers.

Gender bias in the incidence of thyroid cancer is well known, however, the underlying mechanism is largely unknown. The current study determines variations in the molecular characteristics of thyroid cancers between men and women. Normal and cancerous thyroid tissues were collected from a total of 125 men and women who underwent surgical thyroidectomy. Testosterone levels in serum and thyroid cancer tissues were elevated in women while it decreased in men compared to respective control groups; whereas, ligand binding activity increased in men and decreased in women. Androgen receptor (AR) mRNA expression increased in a majority of men while it decreased in a majority of women except those with follicular thyroid carcinoma (FTC). In thyroid cancers of women, Pearson's correlation analysis showed a positive correlation of AR mRNA with AR protein, CBP and Sp1, whereas AR mRNA showed a negative correlation with p53. In case of men, AR mRNA showed a positive correlation with AR and cyclin D1 proteins in papillary thyroid carcinoma (PTC); and CBP and Sp1 in follicular thyroid adenoma (FTA), whereas AR mRNA showed a positive correlation with p53. Our study identified for the first time that AR is posttranscriptionally regulated by miR-124a in thyroid cancer tissues. Further, our in vitro studies with a PTC cell line (NPA-87-1) showed miR-124a as the potent inhibitor of AR that impairs cell proliferation even in the presence of testosterone. Thus, the current study suggests that: (i) the varying pattern of testosterone level and AR status in thyroid tissues of men and women may predispose to the gender specific incidence of thyroid tumors and (ii) miR-124a plays a significant role in determining the AR gene expression pattern and thus, androgen mediated thyroid tumor growth.

Studies on hypoglycaemic effects of polyherbal preparation in streptozotocin-induced diabetic male albino rats.

Many traditional treatments have been recommended in the alternative system of medicine for diabetes mellitus. However, the mode of action of most of the herbals used has not been defined. It has been reported that sex hormones are important regulators of insulin-mediated events in skeletal muscles. In view of this, a novel herbal preparation containing antidiabetic and aphrodisiac plants was used in the present study. Adult male albino rats were divided into following groups after induction of diabetes. Rats were given an intraperitoneal (i.p.) injection of streptozotocin (STZ), at a dose of 65 mg/kg body weight after overnight fasting, to induce diabetic state with blood glucose levels >250 mg/dL. Group 1-Control rats treated with single i.p. injection of vehicle, Group 2-Rats treated with polyherbal preparation (PHP; 500 mg/kg body weight by oral intubation, morning and evening for 30 days), Group 3-STZ-diabetic rats treated orally with equal volumes of vehicle (water) alone and Group 4-STZ-diabetic rats treated with PHP after 10 days of diabetic induction. STZ-diabetes decreased the body weight, serum insulin level and glucose oxidation in liver and skeletal muscles but increased the fasting blood glucose level. After polyherbal treatment, body weight and glucose oxidation were completely restored to control level while serum insulin level was restored partially and the glucose tolerance was significantly improved. There was a significant decrease in total haemoglobin (Hb) level of diabetic rats when compared to control but polyherbal treatment significantly improved the same. However, the other parameters studied (red blood cell [RBC], white blood corpuscle [WBC], packed cell volume [PCV], mean corpuscular volume [MCV] and mean corpuscular haemoglobin [MCH]) were unaltered. In conclusion, the anti-diabetic properties of PHP appear to be mediated through pancreatic beta-cell regeneration, resulting in maintenance of optimal blood glucose and its oxidation in liver and skeletal muscles.

Effects of streptozotocin (STZ)-induced diabetes and insulin replacement on rat ventral prostate.

BACKGROUND: Diabetes mellitus due to insulin deficiency has adverse effect on all organ systems including reproductive organs. Streptozotocin (STZ)-induced diabetes in rats provides a relevant model to study reproductive dysfunction under diabetic conditions, as they exhibit a number of deficits in reproductive function that resemble those seen in humans. The present investigation was designed to delineate the impact of STZ-induced diabetes and insulin replacement on the rat ventral prostate. METHODS: Healthy adult male rats of Wistar strain were divided into three groups: Group I: Control; Group II: STZ-diabetic (rats were treated with a single intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg body weight); Group III: Insulin replaced (after 3 days of STZ treatment, a group of adult male diabetic rats was given insulin at a dose of 3U/100g body weight in two equally divided doses at 08:00 and 18:00 h). All the rats were killed after 20 days of treatment and ventral prostate was removed and processed for biochemical estimations such as glucose oxidation, nuclear and cytosolic androgen and estrogen receptors, fructose, acid and alkaline phosphatases. RESULTS: STZ-diabetes significantly decreased the body weight. Glucose oxidation, androgen and estrogen receptor concentration were also decreased in ventral prostate, but the fructose concentration was increased. Specific activities of both acid and alkaline phosphatases were also markedly decreased due to diabetes. CONCLUSION: The results of this study suggest adverse effects of STZ-induced diabetes on the biochemical profiles as well as androgen and estrogen receptors of rat ventral prostate. Amelioration of these changes (partially or completely) by insulin replacement indicates that optimal insulin is essential for maintaining functional integrity of ventral prostate.