A concept of radiation hormesis: stimulation of antioxidant machinery in rats by low dose ionizing radiation.

OBJECTIVE: The concept of radiation hormesis has been the matter of discussion with regard to beneficial effects to biological systems from low doses of ionizing radiations. However, its molecular basis is not well understood till now and the present study is a step forward to elucidate how low levels of ionizing radiation prove beneficial for functioning of biological systems. MATERIAL AND METHODS: Female Wistar rats weighing 100-120g were divided into four different groups. Each group consisted of eight animals. The animals in Group I served as normal controls for Group II animals which were subjected to whole body X-rays exposure of 20rads and were sacrificed 6 hours following exposure. Group III animals served as normal controls for group IV animals which were given whole body X-rays radiation of 20rads and were sacrificed 24 hours following exposure. RESULTS: The levels of reduced glutathione (GSH), total glutathione (TG) were increased in liver, kidney, brain and blood after 6hrs as well as 24hrs following X-rays exposure. On the contrary, no significant change in the oxidized glutathione (GSSG) content was observed following X-rays irradiation in any of the organs. Further, the low dose of X-rays resulted in a significant decrease in the lipid peroxidation (LPO) in liver, kidney and brain, whereas it caused an increase in LPO levels in blood. The enzyme activities of catalase (CAT) as well as glutathione-S-transferase (GST) were also increased in different organs after X-rays exposure. Furthermore, low dose irradiation with X-rays caused a significant increase in the counts of total leukocytes, lymphocytes and eosinophils, whereas it decreased the counts of neutrophils as well as monocytes. Hence, our results clearly indicate that low dose X-rays radiation exposure stimulates endogenous antioxidant defense machinery and also causes an increase in whole blood lymphocytes and eosinophils responsible for providing key defenses. CONCLUSION: Low doses of X-rays exposure may afford radiation hormesis by providing protection to organs from oxidative injury and support immune reaction.

Evaluation of Tetrofosmin Cold Kit Fractionation Using Alternative New Method of Quality Control for Testing Radiochemical Purity.

Objective The aim of this study is to establish a method for the fractionation of tetrofosmin cold kit under different storage conditions and to optimize an alternate chromatography method from the reference method to test radiochemical purity (RCP). Materials and Methods Tetrofosmin cold kit vial was fractionated aseptically in six equal fractions and stored in vials and syringes. To test the stability of the reconstituted solution for a longer duration, the mother vials and syringes were stored at two different temperatures, that is, at 4°C and at -20°C till further used. Radiolabeling of fractionated tetrofosmin was performed as per the standard labeling protocol. Radionuclide purity, radioassay, and pH were tested. Radiolabeling efficiency and RCP were determined by paper chromatography. Results Radionuclide purity of eluate was greater than 99.9%. The pH of technetium-99m (Tc-99m) eluate and Tc-99m tetrofosmin was between 4.5-7.5 and 7.5-9.5, respectively. The deviation in the radioactivity during all measurements was less than 1%. The kits fractioned in glass vials resulted in higher radiolabeling yield and RCP as compared with kits fractionated in syringes. The RCP of glass vial versus syringe was observed to be greater than 95 versus 90% and 95 versus 80% at -20°C and 4°C, respectively. Conclusion Tetrofosmin kit can be used in a cost-effective manner by fractionation. One tetrofosmin vial can be used in six fractions for up to 15 days when stored at -20°C and 4°C freezer temperature. The alternative method to check the RCP of Tc-99m tetrofosmin is safer and less time consuming as compared with the reference method.

Target Specific Uptake of a Newly Synthesized Radiolabeled 5α-Reductase Inhibitor "Tc-99m-17-Oxo-17a-Aza-D-Homo-5-Androsten-3ß-yl Phenoxyacetate (Tc-99m-17a-Aza Steroid)" in Rat Prostatic Neoplastic Lesions.

Objective: Considering the 5α-reductase (5AR) inhibitory activity of the oximes and the importance of the ester group in increasing the anti-androgenic property, we reasoned to synthesize a compound having a lactam group in ring D and an ester group at the 3 ß position of the androsterone nucleus. The study aims to radiolabel 17-oxo-17a-aza-D-homo-5-androsten-3ß-yl phenoxyacetate (17a-aza steroid) with Tc-99m to evaluate its targeted uptake in experimentally induced prostate carcinogenesis in rats. Materials and Methods: The prediction of the optimal interaction and binding affinity of Tc-99m-17-oxo-17a-aza-D-homo-5-androsten-3 ß-ylphenoxyacetate (Tc-99m-17a-aza steroid) toward 5AR inhibitor was done using Biopredicta Vlife MDS tool. Tc-99m-17a-aza steroid was developed by direct radiolabeling protocol. The radio-pharmacological characteristics (serum stability, plasma protein-binding ability, and lipophilicity) of the complex were evaluated. Further, the bio-distribution studies of the complex were performed in rats with experimentally induced prostate carcinogenesis. Results: The in-silico analysis exhibits favorable binding of Tc-99m-17a-aza toward 5AR with D score-130.97. The radiochemical purity of Tc-99m-17a-aza was 96.79%. The radio-complex maintained stability in the rat serum for a period of 6 h (hours). Plasma protein binding and Log Po/w value were observed to be 86.23 ± 7.08% and 0.118 ± 0.045, respectively. A significantly enhanced percent-specific uptake was observed in the prostate of rats with induced prostate carcinogenesis. Conclusion: The study concludes that Tc-99m-17a-aza exhibits prostate specificity and can be explored further for its potential as a radionuclide imaging probe.

Regulatory role of zinc on the biokinetics and biodistribution of (65)Zn during the initiation of experimentally induced colon cancer.

The present study was conducted to evaluate the kinetics of zinc utilization during the formation of colon carcinoma in an animal model of colon carcinogenesis. The rats were segregated into 4 groups: untreated control, 1,2-dimethylhydrazine (DMH) treated, zinc treated, and DMH+zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 wk. Zinc (in the form of zinc sulphate) was supplemented at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of study. Whole body (65)Zn kinetics followed two-compartment kinetics, with Tb(1) representing the initial fast component of the biological half-life and Tb(2), the slower component. The Tb(1) component showed a significant elevation while the Tb(2) component was significantly diminished in DMH-treated rats, which, however, got normalized following zinc supplementation. The biodistribution and subcellular distribution of (65)Zn was significantly affected in DMH-treated rats when compared to normal control rats. However, zinc significantly reversed the altered (65)Zn uptake in different organs and various fractions of colon. The present study for the first time demonstrated a faster mobilization of zinc during initiation of experimentally induced colon carcinoma and provides a physiological basis for the role of zinc in colon tumorigenesis.

Chemoinformatic Study and In vitro Bioevaluation of Tc-99m-Labeled N-Acetyl Neuraminic Acid in C6 Glioma Cells: Potential Role as a Radionuclide Imaging Probe.

BACKGROUND: To date, the use of sialic acid that are reported to be elevated during malignancy has been largely unexplored for tumor imaging. The purpose of the present study was to study the modeled stable conformers of n-acetyl neuraminic acid (Neu5Ac) and its radiolabeled conjugate (Tc-99m-Neu5Ac) through computational chemistry approach and its in-vitro bioevaluation in rat C6 cell lines. MATERIALS AND METHODS: The Neu5Ac was radiolabeled with Tc-99m using stannous reduction method and the radiochemical purity of Tc-99m-Neu5Ac was determined by instant thin layer chromatography. A Cheminformatic study of Tc-99m-Neu5Ac was performed by using Marvin application of ChemAxon. Glioma cancer cells were taken to evaluate the cytotoxicity and binding efficacy of Tc-99m-Neu5Ac. RESULTS: Cheminformatic studies exhibited that the most stable conformer of Tc-99m-Neu5Ac is 15 kcal/mol more stable energetically over least stable conformer. The radiochemical yield of Tc-99m labeled Neu5Ac was observed to be greater than 90%. Further, the radiolabeled complex (Tc-99m-Neu5Ac)exhibited specificity for C6 glioma with time and concentration dependent cytotoxicity. CONCLUSION: In conclusion, Tc-99m-Neu5Ac has the potential to be exploited as an in-vivo radionuclide probe for tumor imaging.

Ultrastructural changes in rat colon following 1,2-dimethylhydrazine-induced colon carcinogenesis: protection by zinc.

The present study evaluated the modulatory effects of zinc on 1,2-dimethylhydrazine (DMH)-induced ultrastructural changes in rat colon as well as on [(3)H]thymidine uptake and [(14)C]D-glucose metabolism. The rats were segregated into four groups: normal control, DMH treated, zinc treated, DMH + zinc treated. Initiation and induction of colon carcinogenesis was achieved through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 and 16 weeks, respectively. Zinc was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum for two different time durations of 8 and 16 weeks. The study revealed a significant decrease in zinc concentration in serum and colon following DMH treatment to rats, which upon zinc supplementation were recovered to near normal levels. A significant increase in in vitro [(3)H]thymidine uptake was observed following 16 weeks of DMH treatment. Further, a significant increase in the [(14)C]glucose turnover was observed following 8 and 16 weeks of DMH treatment. Simultaneous supplementation of zinc to DMH-treated rats for 16 weeks significantly decreased the uptake of [(3)H]thymidine and [(4)C]glucose when compared to DMH alone-treated rats. Changes in the ultrastructural architecture of colonic cells were evident following both treatment schedules of DMH; however, the changes were more distinguishable following 16 weeks of DMH treatment. The most obvious changes were seen in nuclear shape and disruption of cellular integrity, which upon zinc supplementation was appreciably improved. In conclusion, the study suggests positive beneficial effect of zinc against chemically induced colonic preneoplastic progression in rats.

Influence of extraneous supplementation of zinc on trace elemental profile leading to prevention of dimethylhydrazine-induced colon carcinogenesis.

Trace elemental analyses of cancerous tissue is a less explored field of inquiry in cancer research. If the deficiency or excess of a particular trace element can be linked to the cancer, studies can be initiated to see its controlled administration to check the growth of cancer. The present study explored the prophylactic potential of zinc in experimental colon carcinogenesis and also its interaction with other trace metals, which gets altered during the development of colon cancer. Rats were segregated into four groups viz., normal control, dimethylhydrazine (DMH) treated, zinc treated, DMH+zinc treated. Initiation and induction of colon carcinogenesis was achieved through weekly subcutaneous injections of DMH (30 mg/Kg body weight) dissolved in 1 mM EDTA-normal saline (pH 6.5), for 8 and 16 weeks, respectively. Zinc was supplemented at a dose level of 227 mg/L in drinking water, for 8 and 16 weeks. The elemental analyses of colonic samples were carried out using Energy Dispersive X-Ray Fluorescence technique (EDXRF). Zinc administration to DMH treated rats significantly decreased the tumor incidence, tumor multiplicity with simultaneous decrement in tumor size. EDXRF studies revealed that the concentrations of the elements zinc, chromium, manganese and copper were decreased, whereas the concentration levels of iron were found to be increased in the colon tissues following 8 and 16 weeks of DMH treatment. However, zinc supplementation to DMH-treated rats significantly improved the altered levels of elements when compared to DMH-treated animals indicating the chemopreventive role of zinc. In conclusion, DMH induced colon carcinogenesis is accompanied by altered trace element profile and zinc has a positive beneficial effect against chemically-induced colonic carcinogenesis.

65Zn kinetics as a biomarker of DMH induced colon carcinogenesis.

Dietary factors are considered crucial for the prevention of initiating events in the multistep progression of colon carcinoma. There is substantial evidence that zinc may play a pivotal role in host defense against several malignancies, including colon cancer. The present study was conducted to evaluate the kinetics of (65)Zn utilization following experimental colon carcinogenesis in rat model. Twenty rats were segregated into two groups viz., untreated control and dimethylhydrazine (DMH) treated. Colon carcinogenesis was established through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks. Whole body (65)Zn kinetics followed two compartment kinetics, with Tb(1) representing the initial fast component of the biological half-life and Tb(2), the slower component. The present study revealed a significant depression in the Tb(1) and Tb(2) components of (65)Zn in DMH treated rats. Further, DMH treatment caused a significant increase in the percent uptake values of (65)Zn in the colon, small intestine, kidney and blood, whereas a significant decrease was observed in the liver. Subcellular distribution revealed a significant increase in (65)Zn uptake in the mitochondrial and microsomal fractions following 16 weeks of DMH supplementation. In conclusion, the present study demonstrated a slow mobilization of (65)Zn during promotion of experimentally induced colon carcinogenesis and provides a physiological basis for the role of (65)Zn in colon tumorigenesis, which may have clinical implications in the management of colon cancer.

Membrane fluidity and surface changes during initiation of 1,2 dimethylhydrazine-induced colon carcinogenesis: protection by zinc.

The present study evaluated the modulatory effects of zinc on colonic membrane fluidity and surface abnormalities following 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were segregated into four groups: normal control, DMH treated, zinc treated, DMH + zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum, for the entire duration of the study. Brush border membranes (BBM) were isolated from the colon of rats and the fluidity parameters were assessed by steady-state fluorescence polarization technique using the membrane extrinsic fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH). The translational diffusion was measured by using the excimer formation of pyrene incorporated in the membrane. The results demonstrated a significant increase in the polarization and anisotropy, accompanied by an increase in order parameter in the membrane preparations from the colon of DMH-injected rats. Further, studies with pyrene fluorophore indicated a marked decrease in membrane microviscosity following DMH treatment. However, the alterations in membrane fluorescence polarization and the fluidity parameters were completely restored following zinc treatment. Drastic alterations in colon surface were noticed after 8 weeks of DMH treatment. However, zinc treatment to DMH-treated rats greatly restored normalcy in the colonic surface. The study concludes that zinc has a strong membrane stabilizing effect and thus has a positive beneficial effect against chemically induced colonic preneoplastic progression in rats.

Over-Expression of Cyclooxygenase-2 in Colorectal Cancer Patients.

Background: Colorectal carcinoma (CRC) is the most common neoplasm of the gastrointestinal tract. COX-2 plays an important role in CRC development and is a key target for the regression of colorectal tumorigenesis by nonsteroidal anti-inflammatory drugs. The present study was conducted to examine the relationship of the levels of COX-2 in CRC patients with the clinico-pathological parameters and also to assess its usefulness as a potential biomarker for diagnosis of CRC. Methods: Prior to surgery, 30 CRC patients were enrolled and the samples from colon tumors and surrounding tissues were taken after they underwent surgical intervention at PGIMER, Chandigarh. mRNA expression levels of COX-2 were examined in 30 CRC and adjacent normal colonic mucosa by quantitative polymerase chain reaction (qPCR). The expression of COX-2 was assessed by immunohistochemical method using rabbit polyclonal antibodies against human COX-2 protein. Results: The quantitative relative expression of COX-2 mRNA was observed to be significantly higher (p<0.05) in colorectal cancer tissues as compared to adjacent normal colon tissues. Also, female CRC patients showed significantly higher (p<0.009) expression of COX-2 mRNA vis-a-vis male colorectal cancer patients. This is the first study which has reported a direct relationship between COX-2 mRNA expressions in male colorectal cancer patients versus females. Further, immunohistochemistry of COX-2 confirmed the quantitative real time-PCR findings. Conclusion: Our study shows that COX-2 over expression in colorectal carcinoma patients is closely associated with clinico-pathological parameters and is more pronounced in males versus females. Further, COX-2 mRNA expression can serve as a potential biomarker for the diagnosis of CRC.

Zinc modulates lithium-induced hepatotoxicity in rats.

AIM: The present study explored the hepatoprotective role of zinc in lithium-induced hepatotoxicity. METHODS: Rats received either lithium treatment in diet at a dose level of 1.1 g/kg diet, zinc alone at a dose level of 227 mg/L in drinking water, and combined lithium plus zinc or drinking water alone for different time durations of 1, 2 and 4 months. This study explored the hepatic marker enzymes, antioxidant status and histopathological investigations in the liver of rats following different treatments. RESULTS: The activities of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase were found to be elevated significantly following 2 and 4 months of lithium treatment. Lithium-treated rats showed a significant increase in the levels of lipid peroxidation and superoxide dismutase and a significant inhibition in the levels of reduced glutathione, catalase and glutathione-S-transferase, following 2 and 4 months of treatment. However, zinc co-administration revealed significant improvement in the altered activities of hepatic marker and antioxidant enzymes in comparison with lithium-treated animals. Lithium-treated rats also indicated drastic alterations in hepatic histoarchitecture and zinc co-administration resulted in improvement in the structure of hepatocytes. CONCLUSION: The present study suggests the protective potential of zinc in lithium-induced hepatotoxicity.

Neuroprotective effects of zinc on antioxidant defense system in lithium treated rat brain.

With a view to find out whether zinc affords protection against lithium toxicity the activities of antioxidant enzymes and lipid peroxidation profile were determined in the cerebrum and cerebellum of lithium treated female Sprague Dawley rats. Lipid peroxidation was significantly increased in both the cerebrum and the cerebellum of animals administered with lithium for a total duration of 4 months as compared to the normal control group. On the contrary, the activities of catalase and glutathione-s-transferase (GST) were significantly reduced after 4 months of lithium treatment. The activity of superoxide dismutase (SOD) was significantly increased in the cerebrum after 4 months lithium administration, whereas in the cerebellum the enzyme activity was unaffected. No significant change in the levels of reduced glutathione (GSH) was found in either cerebrum or cerebellum after 2 months of lithium treatment. However, 4 months lithium treatment did produce significant changes in GSH levels in the cerebrum and in the cerebellum. Zinc supplementation for 4 months in lithium-treated rats significantly increased the activities of catalase and GST in the cerebellum, showing that the treatment with zinc reversed the lithium induced depression in these enzyme activities. Though, zinc treatment tended to normalize the SOD activity in the cerebrum yet it was still significantly higher in comparison to normal levels. From the present study, it can be concluded that the antiperoxidative property of zinc is effective in reversing the oxidative stress induced by lithium toxicity in the rat brain.

Cancer Targeting Potential of 99mTc-Finasteride in Experimental Model of Prostate Carcinogenesis.

This study aimed to radiolabel finasteride, a novel 5α-reductase inhibitor, to evaluate its cancer targeting potential in experimental model of prostate carcinogenesis. Finasteride was effectively radiolabeled with 99mTc and showed >90% labeling efficiency. The radiopharmaceutical was found to be stable up to 6 hours in rat serum at 37°C. The blood kinetics of the 99mTc-finasteride followed a biphasic release pattern, whereby fast-release phase was observed at 15 seconds and a slow-release phase was observed after 30 minutes of administration. The plasma protein binding of the radio complex observed was 83.89%. For biodistribution studies, the rats were divided into two groups. Group I served as normal controls, while group II was subjected to carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (T) for induction of prostate carcinogenesis, which was confirmed histopathologically. The biodistribution studies on control and carcinogen-treated rats revealed a significant percent-specific uptake in prostate, which was found to be increased significantly as a function of time. The most significant finding of the study was an increase in the percent-specific uptake in prostate of carcinogen-treated animals when compared to the percent-specific uptake in prostate of normal rats after 2 and 4 hours postinjection. The study concludes that 99mTc-finasteride possesses selectively toward prostate cancer tissue and can be explored further for its role in detection of prostate cancer.

Radiolabeling of cisplatin and its biodistribution in an experimental model of lung carcinogenesis.

This study optimized the radiolabeling of cisplatin with technetium-99m (99mTc) and evaluated its biodistribution in an experimental model of lung carcinogenesis. The percentage labeling of cisplatin with 99mTc was assessed using an ascending chromatographic technique. For biodistribution studies, male rats were divided into 2 groups. The control group received normal saline intratracheally, whereas the treatment group received intratracheal administration of carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) at a dose of 20 mg/kg body weight. The resulting radiopharmaceutical (99mTc-cisplatin) showed 98% labeling efficiency and was found to be stable for up to 6 hours both in both serum and saline under normal conditions. The blood clearance of the 99mTc-cisplatin followed a biphasic release pattern whereby a fast-release phase was observed at 35 seconds and a slow-release phase was observed after 30 minutes of drug administration. The biodistribution studies of control and treated animals revealed high uptake of 99mTc-cisplatin by the liver and slow excretion via the kidneys. However, a time-dependent increase in the lung-to-muscle specific uptake ratio was observed in DMBA-treated rats. The study concluded that 99mTc-cisplatin possesses selectivity toward cancerous lung tissue and can be explored further for its diagnostic potential in the detection of lung cancer and the evaluation of treatment response.

In vitro ¹4C-labeled amino acid uptake changes and surface abnormalities in the colon after 1,2-dimethylhydrazine-induced experimental carcinogenesis: protection by zinc.

The present study explored the regulatory role of zinc on the in vitro uptake of ¹4C-glucose and ¹4C-labeled amino acids and on colonic surface abnormalities after 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were segregated into four groups: control, DMH-treated, zinc-treated, and DMH + zinc-treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks. Zinc (in the form of zinc sulfate) was given to rats at a dose level of 227 mg/L in their drinking water. DMH treatment caused a significant decrease in the activities of disaccharidases (sucrase, lactase, and maltase), but a significant increase in the activity of alkaline phosphatase. In vitro uptake of ¹4C-D-glucose and the amino acids ¹4C-glycine, ¹4C-alanine, ¹4C-lysine, and ¹4C-leucine were significantly higher in the colons of DMH-treated rats. Zinc supplementation of DMH-treated rats resulted in regulating the altered intestinal enzyme activities and in vitro uptake of ¹4C-amino acids and ¹4C-glucose. Scanning electron microscopy revealed drastic alterations in the colon surface morphology after DMH treatment, which were restored after zinc supplementation. Our results confirm a beneficial effect of zinc against DMH-induced alterations in the colons of rats.

Radioprotective role of selenium after single-dose radioiodine (¹³¹I) exposure to red blood cells of rats.

The present study elucidated the protective potential of selenium following ¹³¹I-induced alterations in rat blood. Forty rats were segregated into 4 groups. Animals in Group I served as normal controls, Group II animals were injected with a single dose of 3.7 Mbq of ¹³¹I (carrier free), Group III animals were supplemented with selenium (1 ppm), and Group IV animals were given a combined treatment of selenium and ¹³¹I. ¹³¹I treatment of rats showed significant increases in total leukocyte counts (TLCs), lymphocytes, and neutrophils (monocytes and eosinophils were not recorded). These were significantly restored upon supplementation of selenium. Lipid peroxidase (LPO), glutathione peroxidase (GSH-PX), reduced glutathione (GSH), superoxide dismutase (SOD), and δ-aminolevulinic acid dehydratase (δ-ALAD) were found to be enhanced following ¹³¹I treatment. However, the levels of catalase were found to be decreased. Selenium administration to ¹³¹I-treated rats resulted in significant restoration of these enzyme activities. Scanning electron microscope (SEM) studies also revealed various surface deformities in erythrocytes after ¹³¹I treatment, which upon supplementation with selenium were significantly restored. In conclusion, selenium may prove to be an effective radioprotector following ¹³¹I treatment.

Role of zinc in modulating histo-architectural and biochemical alterations during dimethylhydrazine (DMH)-induced rat colon carcinogenesis.

The aim of the present work was to gain insight into the putative anticancer effect of dietary zinc during 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis. The rats were segregated into four groups, namely, normal control, DMH-treated, zinc-treated, and (DMH + zinc)-treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 12 weeks. Zinc in the form of zinc sulfate was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of the study. The effects of different treatments were studied on lipid peroxidation (LPO), reduced glutathione (GSH), and antioxidative enzymes, which included superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR), as well as on the histoarchitecture of the colon. A total of 12 weeks of DMH treatment resulted in a significant increase in LPO. GSH levels and the activities of SOD, CAT, and GST were found to be significantly decreased following DMH treatment. A significant elevation in the activity of GR was observed following 12 weeks of DMH treatment. Histopathological studies showed well-differentiated signs of dysplasia, which included nuclei enlargement, epithelial thickening, and nuclear pleomorphism indicative of promotional phase of colon carcinogenesis in DMH-administered rats. Administration of zinc to DMH-treated rats decreased the levels of LPO and GSH significantly, but the activities of SOD and CAT were found to be significantly increased following zinc treatment. Zinc supplementation along with DMH treatment did not reveal any significant change in the activity of GR but significantly improved the activity of GST, which was depressed following DMH treatment. Also, zinc treatment in DMH-treated rats showed signs of great improvement, but structureless masses of the cells and hyperchromic nuclei were still visible occasionally. In conclusion, the results of this study suggest that zinc has a positive beneficial effect against chemically DMH-induced colonic preneoplastic progression in rats.

Zinc mediated normalization of histoarchitecture and antioxidant status offers protection against initiation of experimental carcinogenesis.

The present study evaluated the inhibitory effects of zinc on colonic antioxidant defense system and histoarchitecture during 1,2 dimethylhydrazine (DMH) induced colon carcinogenesis in male Spraque Dawley rats. The rats were segregated into four groups viz., normal control, DMH treated, zinc treated, DMH + zinc treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/l in drinking water, ad libitum for the entire duration of the study. Increased lipid peroxidation was accompanied by a decrease in reduced glutathione (GSH), glutathione reductase (GR), glutathione-s-transferase (GST), superoxide dismutase (SOD), and catalase. Administration of zinc to DMH treated rats significantly decreased the lipid peroxidation levels with simultaneous enhancement of GSH, GR, GST, SOD, and Catalase. Histopathological studies from DMH treated rats revealed disorganization of colonic histoarchitecture. However, zinc treatment to DMH treated rats greatly restored normalcy in the colonic histoarchitecture, with no apparent signs of abnormality. Energy Dispersive X-Ray Fluorescence (EDXRF) studies revealed a significant decrease in tissue concentrations of zinc in the colon following DMH treatment, which upon zinc supplementation were recovered to near normal levels. In conclusion, the results of this study suggest that zinc has a beneficial effect during the initiation of key events leading to the development of experimentally induced carcinogenesis.

Effectiveness of zinc in modulating lithium induced biochemical and behavioral changes in rat brain.

1. The purpose of the present study was to determine the effect of zinc on the status of various neurotransmitters as well as behavioral patterns of lithium-treated rats. The study was designed with a view to find out whether zinc affords protection to brain against lithium toxicity. 2. Animals were segregated into four different groups. Animals in group I were fed with standard laboratory feed and water ad libitum and served as normal controls. Animals in group II and IV were given lithium in the form of lithium carbonate in their diet at a dose level of 1.1 g/Kg diet. Animals in group III and IV were given zinc treatment in the form of zinc sulfate at a dose level of 227 mg/L mixed in drinking water of animals. 3. The effects of all the treatments were studied for a duration of 1, 2, and 4 months with regard to the parameters, which included estimation of serotonin and dopamine concentrations as well as the activity of acetylcholinesterase in cerebral cortex of rat brain. Further, passive avoidance, active avoidance, and behavior despair tests were conducted to assess the short-term memory, cognitive behavior, and psychomotor dysfunction of the animals, respectively. 4. Initially, a decrease in the acetylcholinesterase activity was reported in cerebral cortex followed by an increase in the enzyme activity after 2 and 4 months of lithium treatment. Serotonin concentration significantly decreased after 2 and 4 months of lithium treatment, whereas dopamine concentration increased significantly after 4 months of lithium treatment. Zinc administration to the lithium-treated group significantly improved the acetylcholinesterase activity as well as the concentration of dopamine and serotonin. Further, lithium-treated rats showed an increase in depression time as compared to normal controls both after 1 and 4 months of treatment. Short-term memory significantly improved in lithium-treated rats in all treatment groups. However, no change in the cognitive behavior of the animals was reported after lithium treatment. Zinc co-administration with lithium significantly improved the short-term memory and cognitive functions of the animals. From the above results it can be concluded that zinc proved beneficial in altering the status of neurotransmitters as well as the behavior patters of the animals treated with both short and long-term lithium therapy.