Natural Killer cell transcriptome during primary EBV infection and EBV associated Hodgkin Lymphoma in children-A preliminary observation.

Epstein Barr Viral infection is a common childhood infection in India and is also nearly 100 % etiologically associated with pediatric Hodgkin Lymphoma (HL). The main question in EBV immunobiology has been, why only a small subset of infected individuals develop EBV associated malignancies, while the vast majority carry this virus asymptomatically for life. Natural Killer (NK) cells, with a phenotype of CD56dim CD16+ exhibit potent cytotoxicity towards both virus infected cells and transformed cells and hence have been considered to be crucial in preventing the development of symptomatic EBV infection and lymphoma. In order to get an insight into the various possible molecular aspects of NK cells, in the pathogenesis of both these EBV mediated diseases in children we studied the whole transcriptome of MACS sorted CD56dim CD16 + NK cells from four patients from each of the three groups of children viz. Infectious Mononucleosis (IM), HL and age matched controls by using a massively parallel sequencing approach. NK cells from both IM and HL had down-regulated innate immunity and chemokine signaling genes. While down-regulation of genes responsible for polarization of the secretory apparatus, activated NK cell signaling and MAP kinase signaling were exclusive to NK cells in patients with IM, in NK cells of HL, specifically, genes involved in extracellular matrix (ECM) - receptor interaction, cytokine-cytokine receptor interaction, TNF signaling, Toll-like receptor signaling pathway and cytosolic DNA-sensing pathways were significantly down-regulated. Enrichment analysis showed STAT3 to be the most significant transcription factor (TF) for the down-regulated genes in IM, whereas, GATA1 was found to be the most significant TF for the genes down-regulated in HL. Analysis of protein interaction network identified functionally important protein clusters. Top clusters, comprised of down-regulated genes, involved in signaling and ubiquitin-related processes and pathways. These may perhaps be responsible for the hypo-responsiveness of NK cells in both diseases. These possibly point to different deficiencies in NK cell activation, loss of activating receptor signaling and degranulation in IM, versus loss of cytokine and chemokine signaling in HL, in the two EBV associated pathologies investigated. Various suppressed molecules and pathways were novel, which have not been reported earlier and could therefore be potential targets for immunotherapy of NK cell reactivation in both the diseases in future.

Pro-oncogenic, intra host viral quasispecies in Diffuse large B cell lymphoma patients with occult Hepatitis B Virus infection.

Non Hodgkin lymphoma, predominantly Diffuse Large B-cell Lymphoma (DLBCL) has been reported to have a significant association with Hepatitis B virus (HBV). We investigated the presence of different gene segments of HBV in plasma, B-cells and tumor tissues from DLBCL patients and explored the genetic variability of HBV within and across different compartments in a host using Next Generation Sequencing. Despite all 40 patients being HBV seronegative, 68% showed evidence of occult HBV. Sequencing of these gene segments revealed inter-compartment viral variants in 26% of them, each with at least one non-synonymous mutation. Between compartments, core gene variants revealed Arg94Leu, Glu86Arg and Ser41Thr while X gene variants revealed Phe73Val, Ala44Val, Ser146Ala and Ser147Pro. In tumor compartments per se, several mis-sense mutations were detected, notably the classic T1762A/A1764G mutation in the basal core promoter. In addition, a virus surface antigen mis-sense mutation resulting in M125T was detected in all the samples and could account for surface antigen negativity and occult HBV status. It would be interesting to further explore if a temporal accumulation of viral variants within a favored niche, like patients' lymphocytes, could bestow survival advantage to the virus, and if certain pro-oncogenic HBV variants could drive lymphomagenesis in DLBCL.

Bloodstream infections in febrile neutropenic patients at a tertiary cancer institute in South India: A timeline of clinical and microbial trends through the years.

INTRODUCTION: Febrile neutropenia (FN) is an oncological emergency. The choice of empiric therapy depends on the locally prevalent pathogens and their sensitivities, the sites of infection, and cost. The Infectious Diseases Society of America guidelines are being followed for the management of FN in India. METHODS: This is a prospective observational study conducted at a tertiary care cancer centre from September 2012 to September 2014. OBJECTIVES: The objectives of this study were as follows: (1) To review the pattern of microbial flora, susceptibility pattern, and important clinical variables among bloodstream infections in febrile neutropenic patients with solid tumors and hematological malignancies. (2) As per the institutional protocol to periodically review the antibiotic policy and susceptibility pattern, and compare the findings with an earlier study done in our institute in 2010. This was a prospective study conducted from September 2012 to September 2014. RESULTS: About 379 episodes of FN were documented among 300 patients. About 887 blood cultures were drawn. Of these, 137 (15%) isolates were cultured. Isolates having identical antibiograms obtained from a single patient during the same hospitalization were considered as one. Hence, 128 isolates were analyzed. About 74 (58%) cultures yielded Gram-negative bacilli, 51 (40%) were positive for Gram-positive cocci, and 3 (2%) grew fungi. Among Gram-negative organisms, Escherichia coli followed by Acinetobacter baumannii and Klebsiella pneumoniae accounted for 78% of the isolates. Among Gram-positive cocci, Staphylococcus species accounted for 84% of the isolates. We have noted a changing trend in the antibiotic sensitivity pattern over the years. Following the switch in empirical antibiotics, based on the results of the study done in 2010 (when the empirical antibiotics were ceftazidime + amikacin), the sensitivity to cefoperazone-sulbactam has plunged from about 80% to 60%%. Similar reduction in susceptibility was noted for piperacillin-tazobactam, imipenem, and meropenem. On the contrary, there was a marked increase in sensitivity to ceftazidime (50-76%). Based on these results, we have reverted to ceftazidime + amikacin as the empirical antibiotics. CONCLUSION: Every institute must have a regular revision of antibiotic policy based on periodic assessment of the clinical and microbiological profile in FN. This will combat antibiotic resistance.

Plasma Epstein-Barr virus and Hepatitis B virus in non-Hodgkin lymphomas: Two lymphotropic, potentially oncogenic, latently occurring DNA viruses.

CONTEXT: There is a need to study potential infective etiologies in lymphomas. Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal cell functions, and promote cell division. Epstein-Barr virus (EBV) is known to be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been emphasized. AIMS: The aim of this study was to elucidate the association of two potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non-HL (NHL). SETTINGS AND DESIGN: In this prospective study, we estimated plasma EBV and HBV DNA in NHL patients. MATERIALS AND METHODS: Peripheral blood was obtained from newly diagnosed, treatment na ïve, histologically confirmed NHL patients. Plasma EBV DNA was quantified by real-time polymerase chain reaction (PCR) targeting Epstein-Barr Nucleic acid 1 while the plasma HBV DNA was detected using nested PCR targeting HBX gene. In a small subset of patients, follow-up plasma samples post-anticancer chemotherapy were available and retested for viral DNA. RESULTS: Of the 110 NHL patients, ~79% were B-cell NHL and ~21% were T-cell NHL. Plasma EBV-DNA was detected in 10% NHLs with a higher EBV association in Burkitt lymphoma (33.3%) than other subtypes. Pretherapy HBV DNA was detected in 21% NHLs; most of them being diffuse large B-cell lymphoma (DLBCL). Moreover, 42% of DLBCL patients had HBV DNA in plasma. Since all patients were HBV surface antigen seronegative at diagnosis, baseline plasma HBV-DNAemia before chemotherapy was indicative of occult hepatitis B infection. CONCLUSIONS: Our findings indicate a significant association of HBV with newly diagnosed DLBCL.

Plasma Epstein Barr viral load in adult-onset Hodgkin lymphoma in South India.

OBJECTIVE/BACKGROUND: Epstein Barr Virus (EBV) DNA load is increasingly being used as a noninvasive biomarker for detecting EBV association in lymphomas. Since there is a need of data from India, we undertook to prospectively evaluate plasma EBV DNA load as a marker of EBV association in newly diagnosed adult-onset Hodgkin lymphoma (HL). METHODS: EBV DNA was quantified using real-time polymerase chain reaction. In a subset of patients, an assay was validated qualitatively with EBV latent membrane protein-1 (LMP1) immunohistochemistry (IHC). Wherever possible, follow-up plasma samples post three cycles of chemotherapy were obtained. RESULTS: Over a period of 10 months, 33 newly diagnosed adult-onset HL were enrolled in the study. Pretherapy plasma EBV DNA was detectable in ∼49% (16/33) patients (viral loads range, 1.0-51.2×10(3)copies/mL) and undetectable in 30 voluntary blood donors. LMP1 IHC was positive in 56% of cases tested (14/25). Sensitivity and specificity of plasma EBV DNA with respect to LMP1 IHC were 86% and 100%, respectively. Of the eight patients in whom follow-up plasma was available, in five EBV baseline-positive patients EBV load reverted to negative postchemotherapy and corroborated with clinical remission. CONCLUSION: Plasma EBV DNA load estimation may be useful in detecting EBV-association and possibly monitoring the response to therapy in EBV-related HL especially in our country where EBV association of HL is higher than in developed nations.

Febrile Neutropenia in Hematological Malignancies: Clinical and Microbiological Profile and Outcome in High Risk Patients.

BACKGROUND AND OBJECTIVES: Febrile neutropenia (FN) is considered a medical emergency. Patients with hematological malignancies (HM) commonly experience FN. Broad spectrum antibiotics have to be started empirically to prevent complications. This study depicts the clinical profile, microbiological profile, antibiotic sensitivity pattern, and outcome in high risk HM. MATERIALS AND METHODS: In this prospective study, 72 patients with hematologic malignancies, diagnosed and treated for 108 high risk febrile neutropenic episodes from August 2011 to January 2013 at a Regional Cancer Center, in South India were analyzed. Cefoperazone-sulbactum was used as a first-line empiric antibiotic. RESULTS: Majority of the patients with FN episodes had acute myeloid leukemia. Overall culture positivity was 29.62%. The most common organisms isolated were Gram-negative bacilli (63.64%), with Escherichia coli being the most frequent pathogen. All Gram-negative organisms were sensitive to imipenem, whereas sensitivity pattern to other antibiotics were as follows: 85.71%, 78.26%, 69.52%, 63.64%, 41.66% and 47.05% for pipercillin-tazoactum, meropenem, cefoperazone-sulbactum, amikacin, ceftazidime, ciprofloxacin respectively. Overall mortality was 13.5%. Most of the patients responded to empiric antibiotic cefoperazone-sulbactum. CONCLUSIONS: In the hematologic malignancies particularly in acute leukemia, there is high risk of developing FN. Empiric therapy with cefoperazone-sulbactum as a first line leads to satisfactory outcome in high risk FN and therapy should be tailored to the most appropriate antibiotics according to the bacterial culture results.

Cell-free epstein-barr viral loads in childhood hodgkin lymphoma: a study from South India.

Cell-free Epstein-Barr viral (EBV) DNA is detectable in plasma of patients with EBV-related lymphomas. The aim of this study was to evaluate the utility of plasma EBV DNA as a biomarker of EBV association in childhood Hodgkin lymphoma (HL). Furthermore, an attempt was made to evaluate the effectiveness of viral quantitation for assessing response to chemotherapy. Thirteen cases of childhood HL were included in this study. All 13 cases were EBV associated as reflected by expression of EBV LMP1 in the tumor specimen. Eighty-five percent had detectable EBV DNA levels; viral loads ranging from 2.9 to 156.2 × 10³ copies/ml (mean 29 × 10³ copies/ml); while in 2 patients and 30 controls tested, viral DNA was undetectable. In four patients, follow-up samples were available after three cycles of chemotherapy; all had EBV DNAemia prior to chemotherapy but undetectable EBV DNA posttherapy. This corroborated with complete response in these four patients. Plasma EBV viral load quantification maybe a useful tool for detecting EBV association with lymphomas and in monitoring response to treatment in childhood HL in centers with limited resources, more so in India where majority of childhood HL is likely to be EBV associated. This is the first Indian study estimating plasma EBV viral loads in HL.

Primary cutaneous cryptococcosis due to Cryptococcous laurentii in a renal transplant recipient.

We report a patient with primary cutaneous cryptococcosis caused by Cryptococcous laurentii following renal transplantation, probably due to repeated insulin and heparin subcutaneous injections on his thigh. Although cutaneous cryptococcosis due to C. neoformans is well known, reports of skin infections due to non-neoformans cryptococci are uncommon.

Oral histoplasmosis masquerading as oral cancer in HIV-infected patient: A case report.

Histoplasmosis is an endemic mycoses caused by Histoplasma capsulatum with endemicity around midwestern United States and central America. The endemicity of histoplasmosis in India is not clearly known. Histoplasmosis, especially oral histoplasmosis, is now increasingly being reported from India. We report here a culture-confirmed and sequence confirmed, oral histoplasmosis in a HIV seropositive individual who was referred to our regional cancer centre with a suspicion of oral cancer.

Procalcitonin as an adjunctive biomarker in sepsis.

Sepsis can sometimes be difficult to substantiate, and its distinction from non-infectious conditions in critically ill patients is often a challenge. Serum procalcitonin (PCT) assay is one of the biomarkers of sepsis. The present study was aimed to assess the usefulness of PCT assay in critically ill patients with suspected sepsis. The study included 40 patients from the intensive care unit with suspected sepsis. Sepsis was confirmed clinically and/or by positive blood culture. Serum PCT was assayed semi-quantitatively by rapid immunochromatographic technique (within 2 hours of sample receipt). Among 40 critically ill patients, 21 had clinically confirmed sepsis. There were 12 patients with serum PCT ≥10 ng/ml (8, blood culture positive; 1, rickettsia; 2, post-antibiotic blood culture sterile; and 1, non-sepsis); 7 patients with PCT 2-10 ng/ml (4, blood culture positive; 1, falciparum malaria; 2, post-antibiotic blood culture sterile); 3 patients with PCT of 0.5 to 2 ng/ml (sepsis in 1 patient); and 18 patients with PCT < 0.5 ng/ml (sepsis in 2 patients). Patients with PCT ≥ 2 ng/ml had statistically significant correlation with the presence of sepsis (P<0.0001). The PCT assay revealed moderate sensitivity (86%) and high specificity (95%) at a cut-off ≥ 2 ng/ml. The PCT assay was found to be a useful biomarker of sepsis in this study. The assay could be performed and reported rapidly and provided valuable information before availability of culture results. This might assist in avoiding unwarranted antibiotic usage.

Induction of necrosis in cadmium-induced hepatic oxidative stress and its prevention by the prophylactic properties of taurine.

The present study has been carried out to investigate the protective role of taurine against cadmium (Cd)-induced oxidative impairment in murine liver. Oral administration of cadmium chloride (CdCl(2)) at a dose of 4mg/kg body weight for 6 days increased the accumulation of the Cd in the liver and diminished the liver weight to body weight ratio. The CdCl(2) altered the levels of intracellular trace elements, cofactors of various metalloenzymes and increased the activities of serum marker enzymes related to liver dysfunction. In addition, Cd intoxication also attenuated intracellular antioxidant power, the activities of antioxidant enzymes as well as the levels of cellular metabolites. Moreover, level of hepatic metallothionein, lipid peroxidation, protein carbonylation, DNA fragmentation, concentration of intracellular reactive oxygen species (ROS) and the activities of cytochrome P450s have been increased due to Cd toxicity. In addition to the oxidative impairments, Cd exposure caused hepatic cell death mainly via the necrotic pathway. Oral administration of taurine at a dose of 100mg/kg body weight for 5 days prior to CdCl(2) intoxication prevented the alterations of all the toxic-induced hepatic damages. Histological studies also supported the beneficial role of taurine against Cd-induced hepatic damages. Combining all, results suggest that taurine could protect hepatic tissues against Cd-induced oxidative stress probably through its antioxidant activity.

Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury: activation of polyol pathway and oxidative stress responsive signaling cascades.

Diabetic nephropathy is a common cause for end-stage renal disease. Present study investigated the beneficial role of arjunolic acid (AA) against streptozotocin (STZ) induced diabetic nephropathy in rats. Diabetic renal injury was associated with increased kidney weight to body weight ratio, glomerular area and volume, blood glucose (hyperglycemia), urea nitrogen and serum creatinine. This nephro pathophysiology increased the productions of reactive oxygen species (ROS) and reactive nitrogen species (RNS), enhanced lipid peroxidation, protein carbonylation and decreased intracellular antioxidant defense in the kidney tissue. In addition, hyperglycemia activates polyol pathway by increasing aldose reductase (AR) with a concomitant reduction in Na+-K+-ATPase activity. Investigating the oxidative stress responsive signaling cascades, we found the activation of PKCdelta, PKCvarepsilon, MAPKs and NF-kappaB (p65) in the renal tissue of the diabetic animals. Furthermore, hyperglycemia disturbed the equilibrium between the pro and anti-apoptotic members of Bcl-2 family of proteins as well as reduced mitochondrial membrane potential, elevated the concentration of cytosolic cytochrome C and caspase-3 activity. Treatment of AA effectively ameliorated diabetic renal dysfunctions by reducing oxidative as well as nitrosative stress and deactivating the polyol pathways. Histological studies also support the experimental findings. Results suggest that AA might act as a beneficial agent against the renal dysfunctions developed in STZ-induced diabetes.

Arsenic-induced oxidative cerebral disorders: protection by taurine.

The present study was conducted to investigate whether the conditionally essential amino acid, taurine, could play any protective role against the potent neurotoxin arsenic (As)-induced oxidative impairment in the rat brain. Administration in the form of NaAsO(2) (at a dose of 10 mg/kg body weight for 2 days, orally), As increased the intracellular accumulation of metallic As, reactive oxygen species, and super oxide radicals. The toxin also augmented the extent of lipid peroxidation, protein carbonylation, and the levels of glutathione disulphide. Activities of the antioxidant enzymes, membrane-bound enzymes, acetylcholinesterase, and the levels of reduced glutathione, as well as total thiols, have been significantly decreased due to As exposure. Oral administration of taurine (at a dose of 100 mg/kg/body weight for 5 days) was found to be very effective in the prevention of As-induced oxidative impairment in the brain tissue of the experimental rats. To validate the experimental results, a well-known water-soluble antioxidant, vitamin C, was used as the positive control in the study. Combining all, results suggest that taurine plays a beneficial role against As-induced cerebral oxidative stress.

Taurine protects rat testes against NaAsO(2)-induced oxidative stress and apoptosis via mitochondrial dependent and independent pathways.

Arsenic (As) is a well known toxicity inducer. Recent investigations, however, showed that it might have some therapeutic application in cancer treatment. These dual roles of arsenic have attracted a renewed research in organ pathophysiology. In this study, we report that As administration (in the form of NaAsO(2) at a dose of 10mg/kg body weight for 2 days, orally) induces apoptosis in testicular tissue of the experimental rats by the activation of caspase-3 and reciprocal regulation of Bcl-2/Bad with the concomitant reduction of mitochondrial membrane potential and increased level of cytosolic cytochrome C. Arsenite has also been shown to induce activation of mitogen-activated protein kinases (MAPKs), Akt as well as NF-kappaB (p65) in testicular tissue. In addition, As significantly decreased testicular Delta(5)-3beta-HSD and 17beta-HSD activities and reduced the plasma testosterone level, testicular sperm count and sperm motility. Besides, arsenite exposure increased the levels of reactive oxygen species (ROS), serum TNF-alpha, As accumulation and lipid peroxidation and decreased the activities of the antioxidant enzymes and glutathione in the testicular tissue. Oral administration of taurine (at a dose of 100mg/kg body weight for 5 days) was found to be effective in counteracting As-induced oxidative stress, attenuation of testicular damages and amelioration of apoptosis in testicular tissue by controlling the reciprocal regulation of Bcl-2/Bad, phospho-ERK1/2, phospho-p38, phospho-Akt and NF-kappaB. Taurine was also found to play similar beneficial role via mitochondrial dependent pathways in As-induced testicular damages leading to apoptotic cell death.

Protective role of arjunolic acid in response to streptozotocin-induced type-I diabetes via the mitochondrial dependent and independent pathways.

Increasing evidences in both experimental and clinical studies suggest that oxidative stress is involved in the pathogenesis of diabetic tissue damage. Pancreatic beta-cell death is the cause of decreased insulin production in diabetes. Streptozotocin (STZ) is widely used to induce experimental diabetes due to its ability to selectively target and destroy insulin producing pancreatic beta-cells via the formation of both reactive oxygen species (ROS) and RNS (reactive nitrogen species). This study investigated the prophylactic role of arjunolic acid (AA) against STZ-induced diabetes in the pancreas tissue of the Swiss albino rats (as a working model). We observed that STZ administration (at a dose of 65mg/kg body weight, injected in the tail vain) caused increased production of both ROS and RNS in the pancreas tissue of experimental animals. Formation of these reactive intermediates decreased the intracellular antioxidant defense, increased the levels of lipid peroxidation, protein carbonylation, serum glucose and TNF-alpha. Investigating the signaling pathways, we found that STZ administration caused the activation of phospho-ERK1/2, phospho-p38, NF-kappaB and destruction of mitochondrial transmembrane potential, release of cytochrome c as well as activation of caspase 3 in the pancreas tissue keeping the levels of total ERK1/2 and p38 significantly unchanged. Treatment of animals with AA (at a dose of 20mg/kg body weight, orally) both prior and post to the STZ administration effectively reduced these adverse effects by inhibiting the excessive ROS and RNS formation as well as by down-regulating the activation of phospho-ERK1/2, phospho-p38, NF-kappaB and mitochondrial dependent signal transduction pathways leading to apoptotic cell death. Combining all, these results suggest that AA plays some beneficial roles against STZ-induced diabetes.

Taurine plays a beneficial role against cadmium-induced oxidative renal dysfunction.

The present study has been carried out to investigate the role of taurine (2-aminoethanesulfonic acid), a conditionally essential amino acid, in ameliorating cadmium-induced renal dysfunctions in mice. Cadmium chloride (CdCl(2)) has been selected as the source of cadmium. Intraperitoneal administration of CdCl(2 )(at a dose of 4 mg/kg body weight for 3 days) caused significant accumulation of cadmium in renal tissues and lessened kidney weight to body weight ratio. Cadmium administration reduced intracellular ferric reducing/antioxidant power (FRAP) of renal tissues. Levels of serum marker enzymes related to renal damage, creatinine and urea nitrogen (UN) have been elevated due to cadmium toxicity. Cadmium exposure diminished the activities of enzymatic antioxidants, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PD) as well as non-enzymatic antioxidant, reduced glutathione (GSH) and total thiols. On the other hand, the levels of oxidized glutathione (GSSG), lipid peroxidation, protein carbonylation, DNA fragmentation, concentration of superoxide radicals and activities of cytochrome P450 enzymes (CYP P450s) have been found to increase due to cadmium intoxication. Treatment with taurine (at a dose of 100 mg/kg body weight for 5 days) before cadmium intoxication prevented the toxin-induced oxidative impairments in renal tissues. The beneficial role of taurine against cadmium-induced renal damage was supported from histological examination of renal segments. Vitamin C, a well-established antioxidant was used as the positive control in the study. Experimental evidence suggests that both taurine and vitamin C provide antioxidant defense against cadmium-induced renal oxidative injury. Combining all, results suggest that taurine protects murine kidneys against cadmium-induced oxidative impairments, probably via its antioxidative property.

Terminalia arjuna protects mouse hearts against sodium fluoride-induced oxidative stress.

Fluoride is a ubiquitous environmental pollutant. In the current study we have investigated the antioxidative properties of an ethanol extract of the bark of Terminalia arjuna (T. arjuna ethanol extract [TAEE]) against sodium fluoride (NaF)-induced oxidative stress in murine heart. Experimental mice were divided into four groups. The first group served as the normal control. The second group received NaF at a dose of 600 ppm through drinking water for 1 week and served as the toxin control. The third group was exposed to TAEE (at a dose of 50 mg/kg of body weight for 1 week) prior to NaF intoxication, and the last group was treated with vitamin C at a dose of 100 mg/kg body weight for 1 week prior to NaF intoxication and served as the positive control in the study. The activities of various antioxidant enzymes (superoxide dismutase, catalase, and glutathione S-transferase), levels of cellular metabolites, reduced glutathione, and oxidized glutathione, levels of lipid peroxidation end products, and protein carbonyl contents were determined in the cardiac tissues of all the experimental animals. NaF intoxication significantly altered all the indices related to the prooxidant-antioxidant status of the heart; treatment with the active constituents prior to NaF administration, however, prevented these alterations. In addition, the ferric reducing/antioxidant power assay revealed that TAEE enhanced the cardiac intracellular antioxidant activity. Histological studies also demonstrated a cardioprotective action of TAEE. The combined results suggest that TAEE protects murine hearts from NaF-induced oxidative stress, probably via its antioxidant properties.

Cadmium induced testicular pathophysiology: prophylactic role of taurine.

The aim of the present study was to investigate the role of taurine against cadmium induced testicular pathophysiology. Cadmium (in the form of Cadmium chloride, CdCl(2)) administration at a dose of 4 mg/kg body weight for 6 days significantly decreased testicular Delta(5)-3beta-HSD and 17beta-HSD activities along with the reduction in the plasma testosterone level. In addition, reductions in testicular sperm count as well as loss in sperm motility were also observed in Cd-intoxication. Cd increased the intracellular concentration of reactive oxygen species and testicular Cd accumulation. Besides, increased levels of lipid peroxidation, protein carbonylation, glutathione disulfide and DNA fragmentation as well as decreased levels of the activities of the antioxidant enzymes, total thiols and reduced glutathione were also found to be associated with this toxicity. Taurine pretreatment at a dose of 100 mg/kg body weight for 5 days, on the other hand, could prevent all the Cd-induced testicular pathophysiology and oxidative insult related studied parameters. Taurine treatment, in addition also increased the in vivo ferric reducing antioxidant power linearly up to a dose of 100 mg/kg body weight. Histological examination of testicular sections from experimental animals supported these results. The effect of a well established antioxidant, vitamin C has been included in the study as a positive control. Combining all, data suggest that being an antioxidant, taurine plays a beneficial role against Cd-induced adverse effects on the male reproductive system.

Taurine protects the antioxidant defense system in the erythrocytes of cadmium treated mice.

The present study was undertaken to investigate the protective role of taurine (2-aminoethanesulfonic acid) against cadmium (Cd) induced oxidative stress in murine erythrocytes. Cadmium chloride (CdCl(2)) was chosen as the source of Cd. Experimental animals were treated with either CdCl(2) alone or taurine, followed by Cd exposure. Cd intoxication reduced hemoglobin content and the intracellular Ferric Reducing/Antioxidant Power of erythrocytes, along with the activities of antioxidant enzymes, glutathione content, and total thiols. Conversely, intracellular Cd content, lipid peroxidation, protein carbonylation, and glutathione disulphides were significantly enhanced in these cells. Treatment with taurine before Cd intoxication prevented the toxin-induced oxidative impairments in the erythrocytes of the experimental animals. Overall, the results suggest that Cd could cause oxidative damage in murine erythrocytes and that taurine may play a protective role in reducing the toxic effects of this particular metal.