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Cyclooxygenase-2 (COX-2) is an inducible enzyme which triggers the biosynthesis of prostaglandins. COX-2 is activated in response to inflammatory stimuli and is one of the major molecules that is involved in the development and progression of colorectal cancer (CRC). Consistent with such a conceptual framework, it has been shown that COX-2 inhibitors prevent the carcinogenesis of CRC and aid in the treatment of sporadic or familial cases of CRC as shown by an overall increase in the survival rate. However, prolonged use of these inhibitors is associated with increase risk of development of cardiovascular complications, implying that further research is required to identify COX-2 inhibitors that are associated with lower risks of such complications.

Urinary glycoproteins such as Tamm Horsfall Protein (THP) and Osteopontin (OPN) are well established key regulators of renal stone formation. Additionally, recent revelations have highlighted the influence of Endoplasmic Reticulum (ER) and mitochondria of crucial importance in nephrolithiasis. However, till date conclusive approach highlighting the influence of ER stress on urinary glycoproteins and chaperone in nephrolithiasis remains elusive. Therefore, the present study was focussed on deciphering the possible effect of 4-PBA mitigating ER stress on urinary glycoproteins and calnexin (chaperone) with emphasis on interlinking calcium homeostasis in hyperoxaluric rats.Post 9 days of treatment, animals were sacrificed, and renal tissues were investigated for urinary glycoproteins, calnexin, calcium homeostasis, ER environment, redox status, and mitochondrial linkage.4-PBA appreciably reversed the altered levels of THP, OPN, and calnexin observed along with curtailing the disrupted calcium homeostasis when assessed for SERCA activity and intra-cellular calcium levels. Additionally, significant improvement in the perturbed ER environment as verified by escalated ER stress markers, disturbed protein folding-aggregation-degradation (congo red assay) pathway, and redox status was found post 4-PBA intervention. Interestingly, linkage of ER stress and mitochondria was established under hyperoxaluric conditions when assessed for protein levels of VDAC1 and GRP75.4-PBA treatment resulted in rectifying the repercussions of ER-mitochondrial caused distress when assessed for protein folding/aggregation/degradation events along with disturbed calcium homeostasis. The present study advocates the necessity to adopt a holistic vision towards hyperoxaluria with emphasis on glycoproteins and ER environment.

In the present study, N-acetyl neuraminic acid (Neu5Ac) was labeled with 99mTc and its bioevaluation was performed. Radiolabeling of Neu5Ac was obtained with a maximum labeling yield of 93.6% and was confirmed by instant thin layer chromatography, mass spectra (ESI-MS) and high performance liquid chromatography. The resulting radiocomplex showed hydrophilic properties and stability up to 8 h at room temperature in rat serum and saline. Biodistribution and scintigraphic studies exhibited accumulation of activity in the colon of tumor bearing rats. In conclusion, [99mTc]Tc-N-acetyl neuraminic acid exhibits selectivity for neoplastic colon tissue.

The aim of this study was to understand the effects of zinc supplementation on antioxidant defense systems, hematological indices, and erythrocyte morphology in conditions of chronic arsenic toxicity. Male Wistar rats were segregated into four groups: control, arsenic treated, zinc supplemented, and arsenic + zinc treated. The animals in the arsenic-treated group were given arsenic orally in drinking water in the form of sodium arsenite at a dose level of 100 mg L−1, and zinc was administered to zinc-treated animals in the form of zinc sulfate orally in drinking water at a dose level of 227 mg L−1. The animals were subjected to different treatments for a period of 12 weeks, and various investigations were undertaken that included serum zinc content, activity of antioxidant enzymes, and hematological indices. Further, scanning electron microscopic (SEM) studies were performed to assess morphological changes in erythrocytes. Arsenic treatment significantly reduced serum zinc concentrations, which, however, were restored to near-normal levels upon zinc supplementation. The activities of enzymes involved in antioxidant defense systems were altered in the erythrocyte lysates of arsenic-treated rats, which interestingly revealed a significant improvement upon simultaneous zinc supplementation. A significant reduction in the counts of total leukocytes, neutrophils, and lymphocytes was observed following arsenic intoxication, which came back to near control levels following zinc supplementation. Also, protective effects of zinc were evident from SEM that revealed maintenance of topographical appearances of erythrocytes in conditions of arsenic toxicity. Thus, this study clearly shows the protection afforded by zinc on erythrocytes during arsenic-induced toxicity.

Membrane fluidity is the most important physiochemical property of cell membranes and governs its functional attributes. The current investigations were undertaken to understand the potential role of acetyl-11-keto-β-boswellic acid (AKBA), if any, on regulation of membrane dynamics under conditions of benzo(a)pyrene (BaP)-induced lung carcinogenesis in female rats. The animals were divided into five groups which included (I) Normal control, (II) Vehicle treated (olive oil), (III) BaP treated, (IV) AKBA treated and (V) BaP + AKBA treated. BaP was administered at a dose level of 50 mg/kg b.wt. in olive oil orally twice a week for 4 weeks. AKBA was given at a dose level of 50 mg/kg b.wt. in olive oil orally thrice a week for 24 weeks. In addition, AKBA was also administered at a similar dose to BaP-treated animals 4 weeks prior to BaP administration and continued for another 20 weeks. The lipid profile and membrane dynamics were analysed in lung tissue. Total lipids, phospholipids content, membrane fluidity, polarization and order of membrane were significantly (p ≤ 0.001) increased in BaP-exposed animals. However, significant decrease was observed in glycolipids, cholesterol, microviscosity and anisotropy levels compared with normal control animals. Appreciable improvements in above indices were recorded when AKBA was administered to BaP-treated animals. Moreover, the structural variations observed in Fourier-transform infrared spectroscopy spectrum were also normalized in BaP-treated rats with AKBA supplementation. This suggests that the AKBA has a potential role in improving membrane fluidity and associated lipid content in BaP-induced lung carcinogenesis.

The aim of the study was to assess the hepatotoxicity, and therefore pharmacological safety of probiotics Lactobacillus plantarum (AdF10) and Lactobacillus rhamnosus GG (LGG) for potential use in colorectal cancer (CRC) prevention. Thirty‐six female Sprague Dawley (SD) rats were divided into six groups: normal control, AdF10‐ treated, LGG treated, 1,2‐Dimethyl hydrazine (DMH)‐treated, AdF10 + DMH‐ treated, and LGG + DMH‐treated groups. Antioxidant enzyme activity, lipid proxidation, and liver function were assessed. Administration of probiotics in both AdF10 + DMH‐treated and LGG + DMH‐treated groups downregulated DMH induced a rise in lipid peroxide (LPO), glutathione reductase (GR) activity, and increased the diminished glutathione reduced (GSH) content and catalase (CAT), glutathione‐transferase (GST), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. DMH‐treated rats receiving the probiotic treatment suffered less liver damage when compared with rats that did not receive probiotics. In conclusion, the study identifies the use of probiotics as an effective and nontoxic chemo‐preventive interventional in CRC.

Alzheimer's disease is characterized by deposition of amyloid-beta plaques in the brain. Available pharmaceuticals provide temporary symptomatic relief without affecting disease progression. Use of radiation was found effective in treating extra-cranial amyloidosis, therefore, the present study was designed to investigate the neuroprotective role of fractionated X-irradiation in Aβ

Despite recent advances in the treatment of colorectal cancer (CRC), low patient survival rate due to emergence of drug resistant cancer cells, metastasis and multiple deleterious side effects of chemotherapy, is a cause of public concern globally. To negate these clinical conundrums, search for effective and harmless novel molecular entities for the treatment of CRC is an urgent necessity. Since antimicrobial peptides (AMPs) are part of innate immunity of living beings, it is quite imperative to look for essential attributes of these peptides which may contribute to their effectiveness against carcinogenesis. Once identified, those characteristics can be suitably modified using several synthetic and computational techniques to further enhance their selectivity and pharmacokinetic profiles. Hence, this review analyses scientific reports describing the antiproliferative action of AMPs derived from several sources, particularly focusing on various colon cancer in vitro/in vivo investigations. On perusal of the literature, it appears that AMPs based therapeutics would definitely find special place in CRC therapy in future either alone or as an adjunct to chemotherapy provided some necessary alterations are made in their natural structures to make them more compatible with modern clinical practice. In this context, further in-depth research is warranted in adequate in vivo models.

Glutamate excitotoxicity and endoplasmic reticulum (ER) recently have been found to be instrumental in the pathogenesis of various neurodegenerative diseases. However, the paucity of literature deciphering the inter-linkage among glutamate receptors, behavioral alterations, and ER demands thorough exploration. Reckoning the aforesaid concerns, a prospective study was outlined to delineate the influence of ER stress inhibition via 4-phenylbutyric acid (PBA) on α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) excitotoxicity-induced behavioral aspects and possible ER stress-glutamate linkage. Male SD rats were randomly divided into four groups namely sham (surgical control+vehicle, group 1), AMPA-induced excitotoxic group 2 receive a single intra-hippocampal injection of 10 mM AMPA, group 3 received AMPA along with PBA (i.p, 100 mg/kg body weight) for 15 days, and group 4 received PBA alone. Behavioral analyses were performed prior to the sacrifice of animals and hippocampus was extracted thereafter for further analysis. AMPA-induced excitotoxicity exhibited significant impairment of locomotion as well as cognitive functions. The levels of neurotransmitters such as dopamine, homo vanillic acid (HVA), norepinephrine, and serotonin were reduced accompanied by reduced expression of GLUR1 and GLUR4 (glutamate receptor) as well as loss of neurons in different layers of hippocampus. ER stress markers were upregulated upon AMPA excitotoxicity. However, chemical chaperone PBA supplementation remarkably mitigated the behavioral alterations along with expression of glutamate and ER stress intermediates/markers in AMPA excitotoxic animals. Therefore, the present exploration convincingly emphasizes the significance of ER stress and its inhibition via PBA in combating cognitive impairment as well as improving locomotion in excitotoxic animals.

Epigenetic therapy induced by dietary components has become a strong interest in the field of cancer prevention. Olive oil, a potent dietary chemopreventive agent, control colon cancer, however, its role in epigenetic therapy remains unclear. Thus, we aimed to investigate the effect of olive oil in a preclinical model of colon cancer by targeting genetic and epigenetic mechanisms. DMH was used to induce colon cancer in rats; while olive oil was given to separate group of rats along with DMH treatment. Tumor burden and incidence in DMH and DMH + olive oil-treated rats was observed by macroscopic examination and histoarchitectural studies. Potent anti-inflammatory, anti-angiogenic and pro-apoptotic activity of olive oil was explored by gene expression and immunohistochemical studies. The effect of olive oil on epigenetic alterations was examined by detecting promoter methylation with MS-HRM and dysregulation of miRNA by TaqMan MicroRNA Assay. We observed that olive oil administration lowered tumor incidence and inhibited the development of tumors in DMH-treated rats. Olive oil markedly decreased the expression of inflammatory and angiogenic markers and restored the expression of pro-apoptotic markers in DMH-treated rats. Furthermore, the inverse relationship between gene expression and DNA methylation, deviant miRNA pattern and miRNA silencing mediated by aberrant DNA methylation was also seen in DMH-treated rats, which was potentially reversible upon olive oil treatment. Our study concludes that olive oil may play a role in the epigenetic therapy by altering NF-κB and apoptotic pathways via targeting noncoding RNAs and methylation machinery that affecting epigenome to prevent colon carcinogenesis.

Excessive stimulation of ionotropic glutamate receptor is associated with glutamate-mediated excitotoxicity, thereby causing oxidative imbalance and mitochondrial dysfunction, resulting in the excitotoxic death of neurons. Eminent role of endoplasmic reticulum under glutamate-induced excitotoxicity has been highlighted in numerous literatures which have been observed to trigger endoplasmic reticulum stress (ER stress) as well as regulating oxidative stress. However, combating ER stress in excitotoxic neurons can provide a novel approach to alleviate the mitochondrial dysfunctioning and ROS generation. Therefore, we propose to investigate the cross-communication of α-amino-3-hydroxy-5-methyl-4-isoxzole-propionate (AMPA) excitotoxicity-induced oxidative injury with ER stress by employing ER stress inhibitor-4-phenlybutyric acid (4-PBA). Male SD rats were divided into four groups viz sham group (group 1), AMPA (10 mM)-induced excitotoxic group (group 2), curative group of AMPA-induced excitotoxic animals given 4-PBA at a dose of 100 mg/kg body weight (group 3), and alone 4-PBA treatment group (100 mg/kg body weight) (group 4). Animals were sacrificed after 15 days of treatment, and hippocampi were analyzed for histopathological examination, ROS, inflammatory markers, mitochondrial dysfunction, and ER stress markers. AMPA-induced excitotoxicity exhibited a significant increase in the levels of ROS, upregulated ER stress markers, inflammation markers, and compromised mitochondrial functioning in the hippocampus. However, 4-PBA administration significantly curtailed the AMPA-induced excitotoxic insult. This study suggests that targeting ER stress with a chemical chaperone can provide a better therapeutic intervention for neurological disorders involving excitotoxicity, and thus, it opens a new avenue to screen chemical chaperones for the therapeutic modalities.

Lung cancer is a prominent form among various types of cancers, irrespective of the sex worldwide. Treatment of lung cancer involves the intensive phase of chemotherapy/radiotherapy which is associated with high rate of adverse events. There is a need of safe and reliable treatment/adjunctive therapy to apprehend the cancer by reducing the undesirable outcome of primary therapy. Epigallocatechin-3-gallate (EGCG), which is a potent antioxidant and anticancer compound extracted from the plant camellia sinensis has proved to be a novel agent to control or reduce lung tumorigenesis by affecting the signaling molecules of cell cycle regulation and apoptotic pathways. In vitro studies have revealed that EGCG can contain carcinogenesis by altering the molecules involved in multiple signal transduction pathways like ERK, VEGF, COX2, NEAT, Ras-GTPase, and kinases. The animal studies have also demonstrated effectiveness of EGCG by inhibiting various molecular pathways which include AKT, NFkB, MAPK, Bcl/Bax, DNMT1, and HIF-1α. Various attempts have been made to see the adjunctive role of EGCG in human lung cancer. Phase I/II clinical studies have recommended that EGCG is quite safe and effective in providing protection against cancer. In this review, we will discuss the role of EGCG and its molecular mechanisms in lung carcinogenesis.

The present study was designed to investigate the effects of lithium treatment on red blood cells which were given arsenic exposure. Long-term lithium therapy is being extensively used for the treatment of bipolar disorders. Arsenic is a group I carcinogen and a major toxic pollutant in drinking water that affects millions of people worldwide. Male SD rats were segregated into four groups, viz. normal control, lithium treated, arsenic treated, and lithium + arsenic treated. Lithium was supplemented as lithium carbonate at a dose level of 1.1 g/kg diet for a period of 8 weeks. Arsenic was given in the form of sodium arsenite at a dose level of 100 ppm in drinking water, ad libitum, for the same period. Lysates of red blood cells were used to investigate the effects of lithium and arsenic treatments on anti-oxidant enzymes, reduced glutathione (GSH), and lipid peroxidation (LPO) levels. Various hematological parameters, activities of Na+ K+ ATPase and delta-aminolevulinic acid dehydratase (δ-ALAD) were also assessed. A significant reduction was observed in the activities of antioxidant enzymes, GSH levels, total erythrocyte counts, Na+ K+ ATPase, and ALAD enzyme activities in lysates of red blood cells when exposed either to lithium or arsenic. In addition, a significant increase in the levels of malondialdehyde (MDA), lymphocytes, neutrophils, and total leukocytes was also observed following lithium as well as arsenic treatments. However, when arsenic-treated rats were subjected to lithium treatment, a pronounced alteration was noticed in all the above parameters. Therefore, we conclude that lithium supplementation to the arsenic-treated rats enhances the adverse effects on red blood cells and therefore use of lithium may not be medicated to patients who are vulnerable to arsenic exposure through drinking water. It can also be inferred that adverse effects of lithium therapy may get aggravated in patients thriving in the arsenic-contaminated area.

Colorectal cancer is a major cause of cancer-related death in many countries. Inflammatory pathway is considered to play a major role in colorectal carcinogenesis. Nuclear factor kappa B (NF-κB) pathway is a link between inflammation and cancer. NF-κB is a transcription factor which belongs to the Rel family. Activation of NF-κB has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The aim of the present study was to evaluate the expression levels of NF-κB/RelA in colorectal carcinoma using Real-time PCR. For this study, tumor tissue was taken from general surgery OT of PGIMER, Chandigarh from twenty-seven patients of colorectal cancer treated by surgery. Adjacent colonic mucosa specimens were also collected from all patients as normal control tissue. Real-time PCR was performed to determine the nuclear factor-κB/RelA expression levels in twenty-seven pairs of colorectal adenocarcinoma and adjacent normal colonic tissues. Out of 27 CRC patients, 18 were males and 9 females. Mean age of patients was 51.1 ± 14.8 years. Most of the cases were males (67%). Seventy percent of the cases were early (I–II) and 30% were advanced (III–IV) tumor stage. The quantitative relative expression of NF-kB mRNA was found to be significantly higher (p

Hyperoxaluria-induced calcium oxalate crystallisation is associated with the generation of reactive oxygen species (ROS) via mitochondria and NADPH oxidase. Endoplasmic reticulum (ER) has emerged as an organelle which could influence mitochondrial functioning and ROS generation. Plugging an upstream pathway of mitochondrial and NADPH oxidase-induced ROS generation may have better prophylaxis. Therefore, we propose to investigate the linkage of hyperoxaluria-induced ROS generation with ER stress by inhibiting the later with 4-Phenylbutyric acid (4-PBA). Male wistar rats were divided into three groups: a normal control group, an ethylene glycol with ammonium chloride-induced hyperoxaluric group (EA) and a third group which has hyperoxaluric animals given 4-PBA at a dose of 300 mg/kg. After 9 days of treatment, animals were sacrificed and renal tissues were analysed for histopathological examination, ROS, mitochondrial dysfunction, ER stress markers, inflammatory markers and NADPH oxidase subunits expression. Hyperoxaluric rats exhibited a significant increase in the levels of ROS, subsequently up-regulated levels of ER stress markers, inflammatory indicators, NADPH oxidase subunits and compromised mitochondrial functioning. However, ER stress amelioration appreciably curtailed the alterations caused by hyperoxaluric abuse. Therefore, suggesting the major role of ER in hyperoxaluric manifestations thereby providing an opportunity to target ER stress for future therapeutic interventions.

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.

HER2/neu is over expressed in 20–25% of breast cancers. HER2 breast cancers are aggressive and are associated with poor prognosis. The aim of this study was to develop the clinical grade Lu-177-trastuzumab and its preliminary evaluation for specific tumor targeting in HER2 positive breast cancer patients. Trastuzumab was conjugated to bifunctional chelator, DOTA, and characterized for integrity and the number of molecules conjugated. Radiolabeling of DOTA-conjugated trastuzumab was optimized using Lu-177. Quality control parameters including radiochemical purity, stability, sterility, pyrogenicity and immunoreactivity were assessed. A preliminary pilot study was conducted on breast cancer patients (n = 6 HER2 positive and n = 4 HER2 negative) to evaluate the ability of Lu-177-trastuzumab for HER2 specific tumor targeting. The conjugates were efficiently labeled with Lu-177 with high radiochemical purity (up to 91%) and specific activity (6–13 µCi/µg). Lu-177-trastuzumab was stable up to 12 hr post labeling. The radioimmunoassay demonstrated good antigen binding ability and specificity for HER2 receptor protein. The patient studies showed the localization of Lu-177-trastuzumab at primary as well as metastatic sites (HER2 positive) in the planar and SPECT/CT images. No tracer uptake was observed in HER2 negative patients that indicated the specificity of Lu-177-trastuzumab. The study demonstrated that in-house developed Lu-177-trastuzumab has specific targeting ability for HER2 expressing lesions and may in future become a palliative treatment option in the form of targeted radionuclide therapy for disseminated HER2 positive breast cancer.

Introduction Radioisotope methods have shown to be useful in the non-invasive diagnosis of thyroid nodules over the past years. The present prospective study aims to evaluate the efficacy of gamma imaging using single and dual tracer using Tc-99m pertechnetate and Tc-99m tetrofosmin for evaluation and management of thyroid nodules. Methods Dynamic (perfusion) imaging was performed after injecting 148-185 MBq (4-5 mCi) of Tc-99m pertechnetate followed by static imaging. A second, dynamic (perfusion) imaging study within same week was performed with 296-370MBq (8-10mCi) of Tc-99m tetrofosmin on same group of patients followed by early and delayed images. Results of radionuclide perfusion scan from both studies were compared qualitatively with postsurgical histopathology or fine needle aspiration cytology (FNAC). Results Total 65 nodules in 50 patients were included in the study. With single tracer, the specificity and accuracy of Tc-99m pertechnetate was 23% and 45% and for Tc-99m tetrofosmin scan was 40% and 49%. When dual tracers were evaluated for the same group of patients, the specificity was 56% and accuracy was 55%. Conclusion Dual Tracer technique with Tc-99m pertechnetate and Tc-99m tetrofosmin could be helpful in selecting nodules need surgical intervention. This technique can be used for convenient and rapid diagnostic evaluation of thyroid nodules non-invasively. We suggest a combination of fine needle aspiration biopsy and dual use of Tc-99m-pertechnetate and Tc-99m-tetrofosmin as a routine diagnostic approach to thyroid nodules.

Chlorpyrifos (CPF), an organophosphate insecticide has a wider application throughout the world to protect agricultural crops and vegetables from insects. Polyphenolic compounds are considered as beneficial against toxicities induced by organophosphates. The present study was conducted to understand the neuroprotective role of quercetin in chlorpyrifos-induced apoptotic events in rats. Twenty-four male Sprague Dawley rats weighing 170 to 200 g were divided into four groups viz: Control, chlorpyrifos treated (13.5 mg/kg body wt. alternate day), quercetin treated (50 mg/kg body wt. every day) and combined chlorpyrifos + quercetin treated. All the treatments were carried out for a total duration of 60 days. Protein carbonyl content and acetylcholinesterase activity were estimated in serum along with cerebrum and cerebellum to ascertain neurotoxicity. Further, for appraisal of neurodegeneration as a consequence of apoptosis, protein expressions of Bcl-2, Bax, cytochrome c, caspase-8, and caspase-9 were assessed. The results showed that protein carbonyl contents were markedly increased in both serum and brain tissues (cerebrum and cerebellum) of chlorpyrifos-treated rats when compared with control group and were appreciably improved upon simultaneous supplementation with quercetin. Further, chlorpyrifos treatment revealed a significant decrease in the enzyme activity of acetylcholinesterase in serum as well as in cerebrum and cerebellum, which however was increased upon concomitant treatment with quercetin. In chlorpyrifos-treated animals, we have observed a significant decrease in the protein expression level of Bcl-2, but a remarkable increase in the expression levels of Bax, cytochrome c, caspase-8, and caspase-9 in both cerebrum and cerebellum. Interestingly, when chlorpyrifos-treated animals were supplemented with quercetin, a significant increase in the expression of Bcl-2 and an appreciable decline in the expression levels of Bax, cytochrome c, caspase-8, and caspase-9 was observed. In conclusion, the present study advocates that quercetin may prove to be a useful candidate in containing the oxidative-induced apoptotic events during chlorpyrifos exposure.

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.

Pseudomonas monteilii is hypothesized as a rare opportunistic pathogen according to few reports published in the literature. This article reported the genomic features and resistome content of strain P. monteilii CD10_2 that was isolated from the intestinal tissues. Annotation and comparative genomics of strain CD10_2 with P. putida KT2440 was performed to identify it's virulence genes, pathogenicity islands and antibiotic resistance genes. P. monteilii CD10_2 encodes for almost similar genes related to virulence and antibiotic resistance to that of P. putida KT2440 which is well known to cause nosocomial infections in immune compromised patients. Disc diffusion studies confirmed the multi-drug resistant nature of the strain CD10_2 as corroborated by the genomic analysis. Thus, the article has reported a about the multi-drug resistant strain P. monteilii CD10_2 highlighting it as a putative pathogen and it's possible role in the transfer of antibiotic resistance genes from the environment to the human gut.

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 non-steroidal 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

Stroke is an increasingly prevalent clinical condition and second leading cause of death globally. The present study evaluated the therapeutic potential of Indian Ginseng, also known as Withania somnifera (WS), supplementation on middle cerebral artery occlusion (MCAO) induced mitochondrial dysfunctions in experimental model of ischemic stroke. Stroke was induced in animals by occluding the middle cerebral artery, followed by reperfusion injury. Ischemia reperfusion injury resulted in increased oxidative stress indicated by increased reactive oxygen species and protein carbonyl levels; compromised antioxidant system; in terms of reduced superoxide dismutase and catalase activity, along with reduction in GSH levels and the redox ratio, impaired mitochondrial functions and enhanced expression of apoptosis markers. Ischemia reperfusion injury induced mitochondrial dysfunctions in terms of (i) reduced activity of the mitochondrial respiratory chain enzymes, (ii) reduced histochemical staining of complex-II and IV, (iii) reduced in-gel activity of mitochondrial complex-I to V, (iv) mitochondrial structural changes in terms of increased mitochondrial swelling, reduced mitochondrial membrane potential and ultrastructural changes. Additionally, an increase in the activity of caspase-3 and caspase-9 was also observed, along with altered expression of apoptotic proteins Bcl-2 and Bax in MCAO animals. MCAO animals also showed significant impairment in cognitive functions assessed using Y maze test. WS pre-supplementation, on the other hand ameliorated MCAO induced oxidative stress, mitochondrial dysfunctions, apoptosis and cognitive impairments. The results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management.

HER2/neu expressing cancers constitute 30% of all breast cancers. Trastuzumab, a monoclonal antibody, is widely used for the treatment of HER2/neu expressing breast cancers. The aim of this study was to conjugate trastuzumab with a bifunctional chelator, cyclic Diethylene triamine-pentaacetic anhydride (cDTPAA) for radiolabeling with Tc-99m to develop a radio-pharmaceutical for assessment of HER2/neu status for treatment planning and response monitoring post trastuzumab treatment. cDTPAA was conjugated to trastuzumab at various molar ratios (10:1–100:1). The conjugates were purified and characterized for the integrity and number of chelator molecules conjugated. Radiolabeling of cDTPAA-trastuzumab conjugates was done with Tc-99 m and labeling parameters were studied. The quality control of the radiolabeled preparation was carried out by radio thin layer chromatography (TLC). Endotoxin estimation and sterility test were performed. Biodistribution studies were carried out at different time intervals (1 h, 6 h and 12 h) post intravenous injections in normal rats. The average number of molecules conjugated varied from 0.75 to 7.5 for the different molar ratios experimented. Maximum radiolabeling yield obtained was 90%. Post purification radiochemical purity was >95%. The biodistribution studies showed high activity in liver, kidney and blood retention up to the period of 12 h.

99m Tc abstract In the present study, we successfully radiolabeled gefitinib with 99m Tc by direct labeling method. The radio-ligand had radiolabeling efficiency of 495.0% and in vitro stability of 480.0% at 24 h. The radiotracer cleared from blood bi-exponentially. Animal organ biodistribution data indicated hepato- renal excretion of the radiotracer. Scintigraphy carried out in tumor bearing mice (induced by EGFR expressing EAT cell lines) demonstrated that the radiotracer accumulated in the tumor site with T/NT ratio of 3.370.2 at 1 h.

This study was undertaken to evaluate the effect of external metal filters on the image quality of computed tomography (CT) and single photon emission computed tomography (SPECT)/CT images. Images of Jaszack phantom filled with water and containing iodine contrast filled syringes were acquired using CT (120 kV, 2.5 mA) component of SPECT/CT system, ensuring fixation of filter on X-ray collimator. Different thickness of filters of Al and Cu (1 mm, 2 mm, 3 mm, and 4 mm) and filter combinations Cu 1 mm, Cu 2 mm, Cu 3 mm each in combination with Al (1 mm, 2 mm, 3 mm, and 4 mm), respectively, were used. All image sets were visually analyzed for streak artifacts and contrast to noise ratio (CNR) was derived. Similar acquisition was done using Philips CT quality control (QC) phantom and CNR were calculated for its lexan, perspex, and teflon inserts. Attenuation corrected SPECT/CT images of Jaszack phantom filled with 444-555 MBq (12-15 mCi) of (99m)Tc were obtained by applying attenuation correction map generated by hardened X-ray beam for different filter combination, on SPECT data. Uniformity, root mean square (rms) and contrast were calculated in all image sets. Less streak artifacts at iodine water interface were observed in images acquired using external filters as compared to those without a filter. CNR for syringes, spheres, and inserts of Philips CT QC phantom was almost similar to Al 2 mm, Al 3 mm, and without the use of filters. CNR decreased with increasing copper thickness and other filter combinations. Uniformity and rms were lower, and value of contrast was higher for SPECT/CT images when CT was acquired with Al 2 mm and 3 mm filter than for images acquired without a filter. The study suggests that for Infinia Hawkeye 4, SPECT/CT system, Al 2 mm, and 3 mm are the optimum filters for improving image quality of SPECT/CT images of Jaszack or Philips CT QC phantom keeping other parameters of CT constant.

Species of the genus Nesterenkonia have been isolated from different ecological niches, especially from saline habitats and reported as weak human pathogens causing asymptomatic bacteraemia. Here, for the first time we are reporting the genome sequence and pathogenomic analysis of a strain designated as CD08_7 isolated from the duodenal mucosa of a celiac disease (CD) patient, identified as Nesterenkonia jeotgali. To date, only five strains of the genus Nesterenkonia (Nesterenkonia massiliensis strain NP1T, Nesterenkonia sp. strain JCM 19054, Nesterenkonia sp. strain F and Nesterenkonia sp. strain AN1) have been whole genome sequenced and annotated. In the present study we have mapped and compared the virulence profile of N. jeotgali strain CD08_7 along with other reference genomes which showed some characteristic features that could contribute to pathogenicity. The RAST (Rapid Annotation using Subsystem Technology) based genome mining revealed more genes responsible for pathogenicity in strain CD08_7 when compared with the other four sequenced strains. The studied categories were resistance to antibiotic and toxic compounds, invasion and intracellular resistance, membrane transport, stress response, osmotic stress, oxidative stress, phages and prophages and iron acquisition. A total of 1431 protein-encoding genes were identified in the genome of strain CD08_7 among which 163 were predicted to contribute for pathogenicity. Out of 163 genes only 59 were common to other genome, which shows the higher levels of genetic richness in strain CD08_7 that may contribute to its functional versatility. This study provides a comprehensive analysis on genome of Nesterenkonia jeotgali strain CD08_7 and possibly indicates its importance as a clinical pathogen.

Hyperoxaluria is a stress that leads to calcium oxalate crystal deposition which further causes inflammation and renal cell necroptosis. Many studies have linked osteopontin expression with apoptosis and inflammation but so far its association with apoptosis with regard to hyperoxaluria is undiscovered. Moreover, a recent report has suggested that osteopontin induces endoplasmic reticulum stress and subsequently apoptosis in myocytes. In this study, the impact of hyperoxaluria on the modulation of osteopontin expression and endoplasmic reticulum (ER) stress mediated apoptosis in rats is explored. Hyperoxaluria was induced in rats by three different doses viz. ethylene glycol alone, ethylene glycol and ammonium chloride together and third group were fed with hydroxyl-l-proline. After hyperoxaluria induction rats were sacrificed and renal tissue was analysed for crystal depositions, osteopontin expression, inflammation, ER stress and subsequent unfolded protein response intermediates (UPR). Altered histoarchitecture of renal tissue and elevated levels of reactive oxygen species (ROS) along with the presence of calcium oxalate crystals were observed in the hyperoxaluric groups. As expected, inflammation and apoptosis was significantly high in all hyperoxaluria groups. Osteopontin expression showed significant up-regulation following hyperoxaluria. Further, a similar trend between expression of osteopontin and elevated ER stress level was observed. Moreover, UPR intermediates expression was also concurrent with osteopontin levels. It is observed that the extent of calcium oxalate crystal deposition is directly associated with the expression of osteopontin, inflammation and ER stress. The results advocate possible association of osteopontin with ER stress, thus suggesting that the ER could be a new target for developing therapeutic regimes for kidney stones.

HER2/neu is over expressed in 20-25% of breast cancers. HER2 breast cancers are aggressive and are associated with poor prognosis. The aim of this study was to develop the clinical grade Lu-177-trastuzumab and its preliminary evaluation for specific tumor targeting in HER2 positive breast cancer patients. Trastuzumab was conjugated to bifunctional chelator, DOTA, and characterized for integrity and the number of molecules conjugated. Radiolabeling of DOTA-conjugated trastuzumab was optimized using Lu-177. Quality control parameters including radiochemical purity, stability, sterility, pyrogenicity and immunoreactivity were assessed. A preliminary pilot study was conducted on breast cancer patients (n = 6 HER2 positive and n = 4 HER2 negative) to evaluate the ability of Lu-177-trastuzumab for HER2 specific tumor targeting. The conjugates were efficiently labeled with Lu-177 with high radiochemical purity (up to 91%) and specific activity (6-13 µCi/µg). Lu-177-trastuzumab was stable up to 12 hr post labeling. The radioimmunoassay demonstrated good antigen binding ability and specificity for HER2 receptor protein. The patient studies showed the localization of Lu-177-trastuzumab at primary as well as metastatic sites (HER2 positive) in the planar and SPECT/CT images. No tracer uptake was observed in HER2 negative patients that indicated the specificity of Lu-177-trastuzumab. The study demonstrated that in-house developed Lu-177-trastuzumab has specific targeting ability for HER2 expressing lesions and may in future become a palliative treatment option in the form of targeted radionuclide therapy for disseminated HER2 positive breast cancer.

We report here the 2.8-Mb genome of Kocuria palustris strain CD07_3 isolated from the duodenal mucosa of a celiac disease (CD) patient. The genome of the bacterium consists of specific virulence factor genes and antibiotic resistance genes that depict its pathogenic potential.

Arsenic, a poisonous metalloid, is ubiquitous in the environment, and affects nearly all organ systems of animals including humans. The present study was conducted to understand the protective role of quercetin, a natural flavonoid on arsenic-induced oxidative damage in rat brain. Forty male Sprague Dawley rats, aged between 7 to 8 weeks and weighing 150-200 g were divided into four groups viz. normal control, arsenic treated, quercetin treated and arsenic + quercetin treated. Rats in normal control group were given normal food and drinking water. Rats in arsenic treated group were given arsenic daily in the form of sodium arsenite (NaAsO2) in drinking water at a dose of 100 mg/l. Rats in the quercetin treated group were given quercetin, dissolved in distilled water, orally everyday through intubation gavage at a dose of 50 mg/kg body weight. Rats in the combined arsenic + quercetin treated group were given arsenic and quercetin in a similar manner as was given to rats belonging to arsenic and quercetin treated group. After 2 months of treatment, antioxidant defense status and changes in the brain histo-architecture were assessed. A significant increase in the levels of lipid peroxidation and a decrease in reduced glutathione levels were observed in the brain of arsenic treated rats, when compared to the normal controls. Further, decrease in the activities of antioxidant defense enzymes such as superoxide dismutase, glutathione peroxidase, glutathione-s-transferase and glutathione reductase, as well as the activity of enzyme nitric oxide synthase were detected in arsenic treated group, which however were restored to normal levels upon simultaneous treatment with quercetin. Brain tissue of arsenic treated rats, also showed changes at the histo-architectural level which were normalized on simultaneous treatment with quercetin. The study, therefore, reveals that quercetin shall prove to be beneficial in containing the neuro-toxic effects of arsenic.

The present study was undertaken to assess the cumulative effects of curcumin and quercetin in inhibiting the activity of COX-2 alongwith other biophysical parameters such as 3 H thymidine uptake as well as uptake and turnover of 14 C-glucose during BP induced lung carcinogenesis in mice. The mice were segregated into five groups viz., normal control, BP treated, BP + curcumin treated, BP + quercetin treated and BP + curcumin+ quercetin treated. Lung carcinogenesis was induced by a single intra-peritoneal (IP) injection of BP (100mg/Kg body weight). Curcumin and quercetin were supplemented to mice at dose levels of 60mg/Kg body weight and 40mg/Kg body wt in drinking water, respectively. All the treatments were continued for a period of 22 weeks. BP treatment brought about a significant increase in the activities of COX-2. Supplementation of phytochemicals individually as well in combination to BP treated mice brought about moderation in the enzymatic activity which was restored to within normal limits. Further, BP treatment recorded increased 3 H thymidine uptake as well as enhanced 14 C-glucose uptake and its turnover which were reduced significantly following simultaneous treatment with phytochemicals. Therefore, cumulative treatment with curcumin and quercetin has the potential of providing protection against lung cancer by inhibiting the COX-2 activity and moderating the 3 H thymidine uptake as well as 14 C-glucose uptake and its turnover.

The currently available radiopharmaceuticals are not specific for tumor imaging.The present study was conducted to radiolabel doxorubicin with Technetium-99m ([99m]Tc) as a scintigraphic marker of high DNA turnover/intercalation in malignant cells.Labeling was done by direct method and the developed radiotracer was subjected to quality control tests. The blood kinetics, scintigraphy of tumor-bearing mice, and biodistribution were studied after intravenous injection of about 7.4 MBq of [99m]Tc-doxorubicin. The isotime (5 minutes) anterior images were acquired at different time intervals of 1.5, 3, and 4 hours.The labeling efficiency of [99m]Tc-doxorubicin was estimated to be more than 95%. The protein-binding efficiency was greater than 88% and in vitro stability was up to 24 hours. The biodistribution data support the clearance of the radioligand by dual (renal and hepatic) pathways. A semiquantitative data analysis of the anterior images indicated that a focal concentration of the radiotracer was seen in the tumor at 1.5 hours, which persisted in 3-hour and 4-hour images, respectively.This scintigraphic approach, therefore, could be a powerful tool for cancer detection at early stage. The technique, however, needs further validation through animal experimentation and clinical studies.

Curcumin is being widely used both as an herbal drug and a food additive in Asian countries. However, its prophylactic potential in containing certain brain disorders is yet to be fully explored. The present study was conceived with an idea that curcumin may prove to be effective in ameliorating N-methyl N-nitrosourea (MNU)-induced adverse effects in cerebrum and cerebellum of mice. Male laca mice received either intravenous MNU treatment at a dose of 10 mg/kg body weight in sterile double distilled water, curcumin alone 60 mg/kg body weight in drinking water via oral gavage, or combined MNU and curcumin treatment on alternate days for a total duration of 2 months. MNU treatment resulted in significant alteration in neurobehavior, reactive oxygen species, lipid profile and histoarchitecture which showed appreciable signs of improvements upon curcumin supplementation. Therefore, the study concludes that prophylactic treatment with curcumin shall prove to be effective in containing MNU-induced neurotoxicity.

BackgroundDoxycycline (DOX) exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer.Materials & methodsIn the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH) as well as study the effect of DOX-alone on a separate group of rats.ResultsDoxycycline administration in DMH-treated rats (DMH-DOX) unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers.ConclusionThese results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects.

The present study was planned to investigate the antigenotoxic effects of curcumin and piperine separately and in combination against benzo(a)pyrene (BaP) induced DNA damage in lungs and livers of mice. Male Swiss albino mice received curcumin (100 mg kg(-1) body weight) and piperine (20 mg kg(-1) body weight) separately as well as in combination orally in corn oil for 7 days as pretreatments and subsequently, 2h after, BaP was administered orally in corn oil (125 mg kg(-1) body weight). A single dose of BaP to normal mice increased the level of 8-oxo-2'-deoxyguanosine (8-oxo-dG) content and % DNA in the comet tail in the lungs and liver. Pretreatments of curcumin and curcumin plus piperine before administration of single dose of BaP significantly decreased the levels of 8-oxo-dG content and % DNA in the comet tail in both the tissues. Moreover, the genoprotective potential of curcumin plus piperine was significantly higher as compared to curcumin alone against BaP induced DNA damage.

This study explored the efficacy of curcumin and resveratrol in maintaining adequate zinc levels to regulate p21 and cyclooxygenase-2 (cox-2) during benzo[a]pyrene (BP)-induced lung carcinogenesis. The mice were segregated into five groups, which included normal control, BP treated, BP plus curcumin treated, BP plus resveratrol treated, and BP plus curcumin plus resveratrol-treated groups. BP treatment resulted in a significant decrease in the zinc levels and protein expression of p21. On the contrary, the enzyme activity of cox-2 showed a significant increase in the BP-treated mice. Interestingly, combined supplementation of curcumin and resveratrol to BP-treated mice resulted in an appreciable improvement in the zinc levels and protein expression of p21. In contrast, synergistic supplementation with phytochemicals resulted in a significant decrease in the enzyme activities of cox-2 in BP-treated mice. This study, therefore, concludes that combined treatment with curcumin and resveratrol maintains adequate zinc levels and regulates inflammation by cox-2 and cell cycle arrest by p21 during lung carcinogenesis in mice.

This study aimed to evaluate the efficacy of zinc as a nutritional supplement in preventing chlorpyrifos-induced neurotoxicity in rats. The rats were segregated into 4 groups, which included normal controls and chlorpyrifos-treated, zinc-treated, and chlorpyrifos- and zinc-treated animals. Eight weeks of chlorpyrifos treatment resulted in a significant increase in the levels of lipid peroxidation (LPO) and reactive oxygen species (ROS) in both cerebellum and cerebrum as compared to normal animals. On the contrary, the activities of glutathione-s-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), and reduced glutathione (GSH) levels were found to be significantly decreased following chlorpyrifos treatment. Furthermore, chlorpyrifos resulted in anxiety in rats as observed by the elevated plus maze test. In addition, an appreciable decrease was noticed in the muscular as well as locomotor activity of chlorpyrifos-treated animals was noticed by rotarod and actophotometer tests, respectively. However, zinc supplementation to chlorpyrifos-treated animals brought back the already raised levels of LPO and ROS to near normal limits in cerebrum. Moreover, zinc treatment to the chlorpyrifos-treated animals also resulted in a significant improvement in the levels of reduced glutathione, and enzyme activities of GST in both cerebrum as well as cerebellum. Also, improvement was observed in the behavior of chlorpyrifos-treated animals upon zinc supplementation. The present study thus concludes that zinc has potential to act as a neuroprotectant against pesticide-induced neurodegenerative and behavioral disorders but further investigations need to be conducted to understand the exact mechanism of neuroprotection.

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.

Objectives: The present study was undertaken to investigate the possible protective potential of wheatgrass extract against radiation-induced toxicity in peripheral lymphocytes of rats exposed to a fractionated dose of X-rays.Methods: Effects of the X-irradiation with and without wheatgrass were studied on various parameters in peripheral lymphocytes including antioxidant defense system and apoptosis. Male Sprague-Dawley rats were divided into four different groups: Normal control group, X-ray-irradiated group (21 Gy over a span of 7 days), wheatgrass-treated group (80 mg/100 g bodyweight for 2 weeks), and X-rays-irradiated + wheatgrass-treated group. All the biochemical indices which included lipid peroxidation (LPO), reduced glutathione, reactive oxygen species (ROS), and activities of antioxidant enzymes were investigated in lymphocytes. Terminal deoxynucleotidyl transferase dUTP nick-end labeling assay was carried out to assess the apoptosis in lymphocytes following whole-body X-irradiation.Results: Whole-body X-irradiation to rats resulted in significant increase in LPO with concomitant depression of antioxidant enzymes activities, namely, superoxide dismutase, catalase, and glutathione peroxidise (GPx) in lymphocytes. Further, the present study witnessed a significant increase in the number of apoptotic lymphocytes in the X-irradiated animals. However, wheatgrass supplementation lowered the LPO levels, restored cellular antioxidant status, and provided significant protection against radiation-induced apoptosis.Conclusions: Based on these observations, the present study suggests that wheatgrass extract has the potential to be used as an effective radioprotectant against radiation-induced oxidative stress and apoptosis in peripheral lymphocytes of whole-body X-ray-exposed rats.

The influence of zinc (Zn) on the serum levels of triiodothyronine (T(3)), thyroxine (T(4)), thyroid-stimulating hormone (TSH) and sodium (Na), potassium (K), and calcium (Ca) was evaluated following ethanol toxicity to the rats. To achieve this, male Wistar rats (150-195 g) were given 3 ml of 30% ethanol orally, and zinc was given in the form of zinc sulfate (227 mg/l) in their drinking water daily for 8 weeks. Ethanol feeding resulted in a slight decrease in T(3) and T(4) levels and a significant increase in thyroid-stimulating hormone concentration, which may be due to the direct stimulatory effect of ethanol on thyroid. Interestingly, when zinc was given to these rats, all the above levels were brought quite close to their normal levels, thus indicating the positive role of zinc in thyroid hormone metabolism. Serum Zn and Ca levels were found to be reduced, but Na levels were raised upon ethanol feeding. Restoration of normal levels of these metals upon zinc supplementation to ethanol fed rats confirms that zinc has potential in alleviating some of the altered thyroid functions following ethanol administration.

The present study was designed to examine the protective potential of lithium if any in ameliorating the alterations induced by aluminium (Al) on behavioral and neurochemical indices. Al was given orally (100 mg/kg b.wt./day) whereas lithium was administered through diet (1.1 g/kg diet) to rats for a total duration of 2 months. Active and passive avoidance tests revealed significant alterations in the short-term memory and cognitive behavior in rats treated with Al. Further, locomotor as well as muscular activities were also found to be significantly affected. Co-administration of lithium with Al caused significant improvement in the short-term memory, cognition, anxiety, locomotion and muscular activity. Further, Al exposure led to a significant decrease in the acetylcholinesterase activity in both the cerebrum and cerebellum. Monoamine oxidase enzyme activity was significantly increased in cerebrum whereas a decrease was observed in cerebellum after Al treatment. Dopamine and serotonin levels were also found to be significantly decreased but the levels of reactive oxygen species were significantly increased in both the regions following Al treatment. Lithium supplementation to Al treated animals caused a significant improvement in the activities of enzymes acetylcholinesterase and monoamine oxidase which were altered by Al. Further, lithium when given along with Al was also able to regulate the levels of dopamine, serotonin and reactive oxygen species in both the regions and the values were found close to the normal controls. Ultrastructural studies revealed alteration in the structure of synapse after Al treatment. Therefore, the study strengthens the hypothesis that lithium can be used as a neuroprotectant during Al induced neurotoxicity.

This study was carried out to investigate the effects of lithium (Li) supplementation on aluminium (Al) induced changes in antioxidant defence system and histoarchitecture of cerebrum and cerebellum in rats. Al was administered in the form of aluminium chloride (100 mg/kg b.wt./day, orally) and Li was given in the form of Li carbonate through diet (1.1 g/kg diet, daily) for a period of 2 months. Al treatment significantly enhanced the levels of lipid peroxidation and reactive oxygen species in both the cerebrum and cerebellum, which however were decreased following Li supplementation. The enzyme activities of catalase, superoxide dismutase (SOD) and glutathione reductase (GR) were significantly increased in both the regions following Al treatment. Li administration to Al-fed rats decreased the SOD, catalase and GR enzyme activities in both the regions; however, in cerebellum the enzyme activities were decreased in comparison to normal controls also. Further, the specific activity of glutathione-s-transferase and the levels of total and oxidized glutathione were significantly decreased in cerebrum and cerebellum following Al treatment, which however showed elevation upon Li supplementation. The levels of reduced glutathione were significantly decreased in cerebrum but increased in cerebellum following Al treatment, which however were normalized upon Li supplementation but in cerebellum only. Apart from the biochemical changes, disorganization in the layers of cerebrum and vacuolar spaces were also observed following Al treatment indicating the structural damage. Similarly, the loss of purkinje cells was also evident in cerebellum. Li supplementation resulted in an appreciable improvement in the histoarchitecture of both the regions. Therefore, the study shows that Li has a potential to exhibit neuroprotective role in conditions of Al-induced oxidative stress and be explored further to be treated as a promising drug against neurotoxicity.

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.

The effects of zinc on drug-metabolizing enzymes in the liver were examined in male Wistar rats following ethanol intoxication. Rats were orally fed 3 mL of 30% ethanol daily for either two, four, or eight weeks and were orally administered zinc sulfate (ZnSO4.7H2O) at a dose level of 227 mg/L. Levels of reduced glutathione (GSH) and the activities of cytochrome P-450, cytochrome b(5), NADPH cytochrome-C-reductase and glutathione-S-transferase (GST) were determined in liver after two, four, and eight weeks. Significant elevation was observed in the activities of the enzymes of the mixed function oxidase system in response to toxicity induced by ethanol at all the intervals. These effects of were ascribed to the enhanced activity of the microsomal ethanol oxidizing system and the associated increase in reactive oxygen species production. Zinc supplementation to these ethanol-intoxicated animals resulted in normalization of these elevated values significantly, but still they do not attain normal levels. Significant increase was observed in reduced glutathione content in animals after four and eight weeks of ethanol feeding, which appeared to be further elevated in combined zinc and ethanol treatment. Significant elevation in the activity of GST was illustrated on ethanol-fed animals at all the three treatment intervals. Furthermore, the activity of this enzyme was only moderately normalized following zinc treatment. This was accredited to the antioxidant potential of zinc, as well as its ability to induce metallothionein content, which provide protection against the toxic effects of ethanol. To conclude, zinc was able to normalize the effects of ethanol in the liver.

The present study was designed to evaluate the protective role of zinc in attenuating the adverse effects induced by lithium in blood of female Wistar rats. Female Wistar rats received lithium in the form of lithium carbonate in diet at a dose level of 1.1 g/kg diet, zinc alone in the form of zinc sulfate in drinking water at a dose level of 227 mg/L drinking water, or lithium plus zinc treatments in the combined group for a total duration of 2 months. Effects of the treatments were studied on antioxidant defense system, various hematologic parameters, and percentage of 65 Zn-specific activity. Lithium treatment resulted in a significant increase in lipid peroxidation levels but caused a significant decrease in reduced glutathione levels and the activities of catalase, glutathione S-transferase, and superoxide dismutase. Lithium treatment also caused a significant decrease in the activities of aminolevulinic acid dehydratase and Na + K + adenosine triphosphatase. However, it resulted in a significant increase in total leukocyte counts, neutrophils, and lymphocyte counts as well as zinc protoporphyrin levels, whereas a significant decrease in counts of monocytes, eosinophils, and percentage specific activity of 65 Zn in blood and its various fractions was noticed. Furthermore, lithium treatment caused a significant decrease in serum zinc levels. However, zinc supplementation to lithium-treated rats effectively raised the reduced glutathione levels and also normalized lipid peroxidation and the activities of antioxidative enzymes, which included catalase, glutathione S-transferase, and superoxide dismutase. Moreover, zinc supplementation could raise the activities of the enzymes aminolevulinic acid dehydratase and Na + K + adenosine triphosphatase as well as the percentage uptake values of 65 Zn in blood and its fractions. The study suggests that zinc, as a nutritional supplement, has the potential in attenuating most of the adverse effects induced by lithium in rat blood.