Ganeshsunder D. Nadkarni

Role of tissue antioxidant defence in thyroid cancers

Reactive oxygen species (ROS), consisting mainly of superoxide, hydrogen peroxide and hydroxyl radical, have been implicated in many diseases including cancer. ROS have been known to play an important role in the initiation and promotion of multistage carcinogenesis. The cellular antioxidant defence plays a crucial role in neoplastic disease. However, very little is known about the tissue antioxidant defence in thyroid cancers. We therefore undertook a study to assess the role of ROS in the pathogenesis of thyroid cancers. Our samples consisted of post-operated thyroid tissues (normal, goiters, follicular adenomas, follicular carcinomas and papillary carcinomas). The parameters studied were lipid peroxidation (LP), antioxidant enzymes--superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)--and non-protein thiols (GSH). Compared to normal thyroid no changes were seen in goiters. LP was significantly higher in adenomas (16%) and carcinomas (60-69%). SOD was decreased by 15% in adenomas while in carcinomas it increased by 9-12%. GPx was raised in carcinomas by 10-21%. Follicular carcinomas showed a 4% increase in CAT activity while GSH was raised in adenomas and papillary carcinomas by 17%. Thus, in adenomas (initial stage) involvement of superoxide radicals and in carcinomas (later stage) hydrogen peroxide and, possibly, hydroxyl radical involvement cannot be ruled out. These ROS may be responsible for elevated LP observed in adenomas and carcinomas.

Hepatic antioxidant enzymes and lipid peroxidation in carbon tetrachloride-induced liver cirrhosis in rats

Liver cirrhosis was induced in rats by the combined action of oral phenobarbitone and inhalations of carbon tetrachloride vapors. These rats manifested hepatosplenomegaly, hypoalbuminemia, and 2- to 17-fold elevations in serum transaminases and alkaline phosphatase levels. The hepatic antioxidant enzymes, superoxide dismutase and catalase, showed 28 and 60% decreases, respectively. There was, however, no increase in the hepatic lipid peroxidation. These studies suggest that in cirrhosis liver cell damage may result due to the direct attack of the oxygen free radicals. Lipid peroxidation in the liver may not be a prerequisite for the development of cirrhosis, as is generally believed.

Reactive oxygen species involvement in ricin-induced thyroid toxicity in rat

1 Ricin is known to have diverse effects on the cells of different organs like liver, kidney, pancreas, intestines and parathyroid. 2 Acute decrease in serum thyroid hormone levels 24 h after ricin administration (1.5 μg/100 g) led us to suspect the toxic action of ricin on the thyroid. 3 We monitored the lipid peroxidation (LP) and anti oxidant status of the thyroid tissue to determine the role, if any, played by reactive oxygen species (ROS) in this pathology. 4 An increase of 39% in LP and 47% in superoxide dismutase, along with a 8.5% decrease in catalase points to the imbalance in the antioxidant defence involving hydrogen peroxide and its univalent reduc tion product, the hydroxyl radical. 5 Thyroid histopathology shows destruction of thyroid follicles and necrosis, which may be due to ROS and may partly explain the 50% reduction in circulating thyroid hormones seen after ricin administration.

Effect of acute ethanol administration on rat plasma protein synthesis.

Abstract Plasma albumin synthesis was inhibited within 1.5 hr of oral administration of ethanol (4 ml/kg) to adult rats. The inhibition was temporary however, as albumin synthesis returned to normal at 3.0 hr and rose significantly thereafter. In contrast, the same dose of ethanol, administered intraperitoneally, did not inhibit albumin synthesis. Fibrinogen synthesis was stimulated by ethanol administration, the effect being observed after 3 hr. The effect of ethanol on total plasma proteins was similar to that on albumin. It is concluded that the effect of ethanol on plasma protein synthesis is dependent on the level of ethanol attained in the blood, which is influenced by the route of administration. The reversal of the initial inhibition and subsequent elevation of synthesis by ethanol may be mediated by the pituitary-adrenal and pituitary thyroid axis.

Antioxidant and free radical-scavenging enzymes in chronically ethanol-consuming rats: controversy over hepatic lipid peroxidation

In rats given ethanol 20% (v/v) in drinking water the hepatic antioxidant enzymes, superoxide dismutase (SOD), catalase and glutathione peroxidase were assayed at the end of 4 and 10 months of ethanol consumption. Simultaneously hepatic lipid peroxidation was monitored. At 4 months SOD and catalase were unaffected, while glutathione peroxidase was decreased by 48%. By the end of 10 months SOD had declined by 16% and glutathione peroxidase activity increased by 49%, while catalase again remained stable. However, hepatic lipid peroxidation was not significantly affected throughout the study. The controversy in the literature over the conflicting results of hepatic lipid peroxidation in chronically ethanol-fed rats is discussed in the light of mode, dose, duration of ethanol consumption, nutritional status of the rat, and primacy of glutathione peroxidase.

Effect of ethanol on turpentine-induced acute phase response in rats

Turpentine-induced acute-phase response and its modulation by ethanol in rats at 48 hr has been studied. There was more than 2.3-5.1 fold increase in fibrinogen and seromucoids concentrations in plasma, accompanied by 28% decline in albumin concentration in turpentine-stimulated rats. The fractional synthesis rate of these two acute-phase proteins was increased by 4.1-6.4 fold, while that of albumin (non acute-phase protein) was reduced by 32.6%. Ethanol inhibited this induction of acute-phase protein synthesis at 48 hr. The inhibition of acute-phase response by ethanol was significantly more pronounced for seromucoids than for fibrinogen and appeared to be dependent on the carbohydrate content of the acute-phase glycoprotein.

Altered hepatic function in vitamin D-deprived rats

Rats were rendered vitamin D-deficient by housing them in a room free of ultraviolet light and maintaining them for 20 weeks on a diet devoid of only vitamin D. The vitamin D-deficiency state was confirmed by the undetectable levels of circulating vitamin D metabolites, severe hypocalcaemia and significantly reduced intestinal calcium transport. Liver function and protein metabolism in these rats were assessed by bromosulphthalein (BSP) clearance, liver histology, plasma transaminases and alkaline phosphatase, and 14C-labelled amino acid incorporation into liver and plasma proteins. Subtle alterations in hepatic function, as manifested by delayed BSP clearance, elevated levels of plasma transaminases and alkaline phosphatase, were noticed. Liver histology revealed changes consistent with periportal necrosis. Synthesis of liver and plasma proteins were reduced by 26-34% (P less than 0.01), without affecting the circulating levels of plasma proteins, suggesting reduced protein turnover in vitamin D-deprived rats. The results strongly suggest the direct/indirect involvement of vitamin D in mediating the altered liver function.

Direct synthesis rates of liver-formed plasma proteins by two methods: A comparative study

Abstract Albumin synthesis rates in humans, based on precursor-product relationships have been estimated by two different methods, namely plasma urea method and urine urea method. The results of the two methods have been shown to correlate well. The advantages of urine urea method have been emphasised.

Binding of 99Tcm sulphur colloid to blood components: implications in renal transplant rejection

The percentage binding of 99Tcm sulphur colloid to blood components (formed elements and plasma proteins) was studied within 1 min of the intravenous injection of the radiopharmaceutical in humans as well as rats. In humans, 68% of the total blood counts were bound to the formed elements (erythrocytes, leucocytes and platelets). The binding pattern (as percentage of plasma counts) among the plasma protein fractions in humans was as follows: albumin, 9.85 +/- 2.06; fibrinogen, 56.70 +/- 7.96; and total proteins, 66.55 +/- 7.32. Activity bound to fibrinogen represented 82.3 +/- 9.1% of the total protein-bound activity in humans. In rats as well fibrinogen was the predominant binding protein (73.8 +/- 5.6). The significant binding of the 99Tcm sulphur colloid to plasma fibrinogen and formed elements of blood may be one of the reasons for the uptake of this radiocolloid in renal transplants before rejection.

An inexpensive method for the acquisition of external standard quench correction capability

Abstract A simple and economical method of acquiring external standard quench correction capability for liquid scintillation counters is described. The technique utilises a commercially available, weak ( 137 Cs source, sealed in glass and used in conjunction with a flat-bottomed, 55 × 15 mm glass tube positioned in the centre of the conventional 20 ml scintillation vial. Each sample is counted with and without the 137 Cs source in place and the counts added by the external standard are analysed in two channels. The external standard channels ratio and external standard gross counts so obtained have been found to be linearly related to 14 C counting efficiency for both chemical and colour quenched samples.