Search

Introduction: Male infertility (MI) in about 50% of couples is constituted due to genetic, hormonal, and epigenetic factors. Almost 10% of it is contributed to genetic anomalies. Objectives: This study was undertaken in 787 males with infertility and the impacts of the type of translocations in these cases were studied in relation to MI. Materials and Methods: Five milliliters (ml) of blood were drawn from referred cases suspected with MI and were used for cytogenetic analysis with Giemsa stain following International System for Human Cytogenetic Nomenclature. Results: Of 6142 referral cases, 787 were detected with MI (787/6142; 12.8%). Forty-four translocations (44/787; 5.6%) were detected in 787 infertile men. Other chromosomal abnormalities were 21% (167/787) in them. Among all translocations, an autosome-autosomal translocations were higher in frequency (24/787; 3.1%) than Robertsonian (15/787; 1.9%) and autogonosomal translocations (5/787; 0.6%). Few translocations seemed to be rare as our knowledge is concerned. Maharashtra had high frequency of translocations followed by Delhi union territory (UT) and Gujarat (07 each) and other states. Most of the translocations were related to infertility. Seven males had primary infertility (7/44) and six with secondary type (6/44) in this study. Conclusions: These reciprocal translocations are important in causation of infertility affecting testicular spermatogenesis. Few are rare in our study. Such cases are clinically suggested for counseling before adopting assisted reproductive technologies.

Hydatid disease is caused by the adult and the larval stage of tapeworms belonging to the Echinococcus species. The major sites of its infection are the liver and lungs. Rarely, it affects the pelvic region including the ovary, accounting for 0.2–2.25%. The primary ovarian site is a rare finding. We report here a case series of two cases with hydatid cysts as the left ovarian and tubo-ovarian masses. In case 1, a 30-year-old woman complained about lower abdominal pain with swelling and had a 7-month-old child and amenorrhea. Ultrasonographic report exhibited multiple cysts in the ovary. In case 2, a 23-year-old female was having primary left ovarian mass and clinically reported an ovarian dermoid tumor after ultrasound scan and had abdominal lump with pain. Her vital indices were normal. The biopsy was sent for further investigation.

Background: Y chromosome microdeletions provide a pivotal role in the control of spermatogenesis. These are located on the q arm of it, specifically, the azoospermia factor (AZF) region, hence named as Yq microdeletions. The mutations in this region are related to testicular pathologies such as azoospermia, oligozoospermia, and other semen categories. Objectives: This study was undertaken to review these microdeletions, screening, and their correlation to semen categories in relation to the Indian and Global populations in context to male infertility, future strategies, and its implications. Methodology: These deletions are screened using sequence-tagged sites (STS) of the European Academy of Andrology (EAAs) and Non-EAAs with polymerase chain reaction technology. The data included were Indian and Global studies obtained from research articles, abstracts, and reviews (75) indexed in Google Scholar, PubMed, and Scopus. Results: A number of total 45,562 Y chromosomes were analyzed. In India, this frequency contributes to 8.33% (453/5435) against the average frequency of 6.96% (3170/ 45562) worldwide. Globally, this frequency was higher (9.1%) in the North American continent. Among all types of deletions, AZFc deletions are higher followed by b, a, b+c, and others as well as are related to azoospermia than oligospermia and other semen cases/categories globally including India. In India, the data on partial deletions are scanty. Further, cases with AZFc are better suitable for assisted reproductive technologies after counseling. Conclusion: Evaluation of correct deletion type to a specific testis pathologic phenotype is suggested for sperm retrieval to correct the male partner. This study is hence better suitable for azoospermia with AZFc deletion around the Global and Indian scenario in association with male infertility. Future strategies are thus called for successful treatment of a specific microdeletion clinically in the male.

Background: Y chromosome microdeletions are one of the genetic causes of male infertility. Evaluation of this is important clinically to assist couple with such genetic defects using polymerase chain reaction-based sequence-targeted-site (STS). Objective: The objective of the study was to evaluate Yq microdeletion in suspected infertile male patients referred to our genetic center. Materials and Methods: European Association of Andrology STS markers for azoospermia factor (AZF) region were used to analyze these anomalies. In addition to semen analysis, cytogenetic, and hormonal studies have also been carried out using respective techniques. Results: Three of 41 cases (7.3%) included in our study had Yq microdeletion, of which one case was of azoospermia and two cases of severe oligozoospermia in AZFa and AZFc subregions were detected. Hormonal levels and karyotypes were unchanged. Conclusion: Yq microdeletion in our study exhibited is similar to Maharashtra, but it varies region-wise and ethnicity, including across Indian populations. Such couples require counseling before opting assisted reproductive technologies.

Background: Hetero atom containing compounds are well studied class of organic compounds exhibits variety of properties and applications. Design and synthesis of new heterocyclic compounds are always of great interest in synthetic and medicinal organic chemistry. Benzothiazole or 2-aminobenzothiazole scaffold based derivatives were reported to display a wide range of biological activities including anticancer, anti-tubercular, antiviral, fungicidal, etc. On the other hand, 1,3,4-oxadiazoles were permit to increase their biological activities due to H-bonding with receptors. These derivatives possess diverse biological activities which include anticancer, antiviral, antifungal, antibacterial and antidepressant etc. Due to interesting biological activity information of about these hetero cyclic moieties, benzothiazole/2-aminobenzothiazole and 1,3,4-oxadiazoles moieties, we chose to design a new series of heterocyclic compounds by mimicking these two types of scaffolds in a single molecule for our study. Methods: The 1,3,4-oxadiazole linked benzothiazole derivatives were synthesized by condensation of, 2-(4-(5-(benzo[d]thiazol-2-yl)-1,3,4-thiadiazol-2-yl)-2,6-dimethoxyphenoxy)acetohydrazide and POCl3 under reflux conditions. All these ten compounds structures were confirmed by spectral data 1H & 13C NMR, Mass, CHN analysis etc. Further, these compounds were evaluated for their anticancer activity against four human cancer cell lines, A549, MCF7, A375 and HT-29 in comparison to CA4 as a reference drug. We also carried out docking studies of these compounds in the Colchicines binding site of Tubulin (PDB_ID: 1SA0) using Glide docking tool indicated that the ligands show good interactions with active site residues. Results: A new series of 1,3,4-oxadiazole fused benzothiazole derivatives were synthesized successfully in totally six steps starting with 4-hydroxy-3,5-dimethoxybenzoyl chloride. All these newly synthesized compounds structures were confirmed by spectral studies and elemental analysis. As we designed for anticancer activity, they were assessed for their anticancer activity against four human cancer cell lines in comparison to a reference drug CA4. As expected, all the ten compounds exhibited anticancer activities against four cancer cell lines with half maximal inhibitory concentration (IC50) values ranging from 0.01 µM to 12.3 µM. The docking studies indicated all the compounds exhibited good binding energies with the receptor. Conclusion: In this study we designed a new series heterocyclic compounds by mimicking two types of scaffolds benzothiazole/2-aminobenzothiazole and 1,3,4-oxadiazoles moieties in a single molecule based on their biological activity in the literature. They were synthesized successfully and molecular structures were confirmed by spectral studies. As expected, all the compounds exhibited anticancer activities against four cancer cell lines. This study can provide a roadmap for design and synthesis of new drug molecules for antitumor and anticancer activity.

Melatonin (MLT) is an extraordinary antioxidant, which plays an important role in reducing reactive oxygen species (ROS) by scavenging them directly or indirectly. Mercury (Hg) is a heavy metal, which induces cytogenetic alterations via various mechanisms, leading to genotoxicity. It induces genotoxicity by enhancing the ROS chiefly. In the present study, the antigenotoxic effect of MLT was evaluated against mercuric chloride (HgCl2). All experiments were conducted in vitro in peripheral blood lymphocytes. Blood cultures were exposed to various concentrations of HgCl2 (2.63, 6.57, and 10.52 microM) for 24 h to study a range of genotoxic parameters. MLT (0.2 mM) supplementation, alone and in combination with the high concentration of Hg, was administered to blood cultures for 24 h. Genotoxic parameters, such as chromosomal aberrations (CAs; structural aberrations (chromatid gaps and breaks, chromosomal gaps and breaks) and numerical aberrations), micronuclei (MNs), and comet assay, were evaluated and analyzed using suitable statistical analysis. Hg treatment revealed a significant increase in CAs, MNs, and comet length. Co-supplementation of MLT along with Hg showed marked protection of these genotoxic end points in treated cultures. In conclusion, our findings suggest that MLT protects against Hg-induced augmentation in genotoxic indices because of its antioxidant property.

Several studies documented the ameliorative effects of curcumin which plays a pivotal role in radical scavenging activities. It also participates in various cellular pathways and interacts with multiple targets. In the present study, we investigated the ameliorative effect of curcumin upon chromosomal genotoxicity induced by cyclosporine, an immunosuppressant, using in vitro approaches. A plausible mechanism of how curcumin mitigates the genotoxic implications of cyclosporine was ascertained using in silico tools. We observed that the curcumin reduces the genotoxic consequences made by cyclosporine upon cell cycle checkpoints and associated chromosomal/DNA manifestations. In addition, we presented the mechanistic details of curcumin interaction with various biomacromolecule types using docking experiments which showed that the possible radical scavenging activities can only be emerged by inducing the expression of antioxidant enzymes, supported by available experimental evidences. We anticipate that the induction of antioxidant enzymes by curcumin would activate Nrf2-Keap1 pathway as the plausible mechanism to exert anti-inflammatory response as demonstrated in renal epithelial cells.

The dengue fever is a debilitating arthropod-borne disease caused by one of the four closely related dengue viruses. The symptoms appear 3 – 14 days after mosquito bite and range from mild fever to...

In the present study, the interaction of the calix[4]resorcinarene polyhydrazide (CPH) capped nanoparticles (CPH-AuNps) and (CPH-AgNps) with different amino acids like arginine, aspartic acid, glutamic acid, glycine, leucine, methionine, histidine, tryptophan and cysteine has been studied by using UV–vis and fluorescence spectroscopy. CPH-AuNps and CPH-AgNps were found to be the selective and sensitive fluorescent probe for l -DOPA and histidine, respectively. The minimum detectable limit for both l -DOPA and histidine was found at 10 nM by a facile way of fluorescence quenching i.e. by a turn off mechanism. CPH-AuNps and CPH-AgNps have also been studied for their antioxidant activity and interaction with DNA by UV–vis spectrophotometry. Furthermore, electrophoresis technique confirmed the interaction of ethidium bromide (EtBr) intercalated CT-DNA and S-DNA with CPH-AuNps and CPH-AgNps, respectively. The simplicity, sensitivity and specificity for the detection of amino acids by the CPH-AuNps and CPH-AgNps, indicates that the synthesized nanoparticles can be used as nano biosensor, with a potential prospect in the biomedical analysis.

A report in a Gujarati family in Western India consisting of rare co-inheritance of β-thalassemia (β0/β+) in a proband, son was identified. The trio samples, parents and son, of extracted D...

Background and Objectives: Aneuploidy is one of the major concerns to cause genetic anomalies. This condition is mostly related to addition and/or deletion with respect to set(s) of chromosomes. Here, we report an analysis of 5740 referral cases during three consecutive years (2015 – 2018) from our Diagnostic Research Center, Ahmedabad for aneuploidy pattern. Methodologies: The patients were asked to fill the necessary forms and their blood (5ml) was drawn for chromosomal studies using the Karyotyping following International System for Human Cytogenetic Nomenclature (ISCN) manual. Results: The data revealed the numerical aberrations for only aneuploidy detected was (3.7%; 211/5740). In this report, constitutional (c) autosomal aneuploidy was 75% (158/211). The total mosaic cases were nine (9/211) comprising constitutive (2) and acquired (7) aneuploidy cases. In autosomal aneuploidy, cT21 was higher (96%; 152/158) than others (4%; 6/158) comparatively. Among cT21 (152), males (76%; 115/152) were more affected than females (24%; 37/152). These statistical data also revealed that acquired chromosomal aneuploidy (leukemia) possessed (25%; 53/211); with more mosaic cases (7/211). Conclusion: Couples with such conditions are eligible for genetic tests and counseling as well as new strategies are urgently to be undertaken by governmental organizations (GOs) and non-governmental organizations (NGOs) for affected families with better personalized and informed decision making. The significance of these data is thus discussed in relation to genetic disorders caused by constitutional and acquired aneuploidy of leukemic blood in this report.

Background and Objectives: Human cell nucleus has, the genome consisting of euchromatin and heterochromatin. The euchromatin has gene-rich and actively functional. The heterochromatin has two components namely constitutive and facultative, where the former is highly polymorphic. It is related to numerous diseases like cancer and infertility which is now well known, though it was earlier thought to be inactive; hence the implication of these polymorphic variants of chromosomes is reviewed with respect to acrocentric and non- acrocentric types. Methodologies: The polymorphic variants can be detected by C, G, Q and R banding techniques. We usually follow G band preparation of karyotypes following World Health Organisation (WHO) manuals and their role in cancer and reproduction is reviewed. Review and Conclusion: It is emphasized that most of the p and q arms of 1, 9, 16, D and G groups and X, Y chromosomes exhibited polymorphism which are related to cancerous and infertile conditions in both sexes. Data on few non-acrocentric chromosomes like 2, 4, 8, 10, 12, 18, 19 and 20 are not available. Our review however indicated that the evaluation of specific heteromorphic variants needs to be detected using specific probes for confirmation of anomaly to assist affected cases, though earlier data indicated ambiguous information with few cases analyzed regarding assisted reproductive technologies and malignancy condition. This appraisal thus would play a key role in human chromosomal heteromorphic abnormalities and recommend genetic tests and counseling ultimately made available to the affected cases.

Present study represents a novel approach of PCR ready-human DNA extraction method from skeletal remains using copper nanoparticles (CuNPs) for personnel identification. To achieve rapid, cost effective, sensitive and non-hazardous method for DNA extraction we utilized CuNPs synthesized using microwave. The applicability of this approach was first tested in blood samples and afterwards, this system was extended to skeletal remains' samples also. This method yields good quality DNA that are ready for PCR reactions from small quantities of blood and skeletal remains. Consequently, even small quantities of nanoparticles could be potentially utilized for a highly efficient isolation of DNA from skeletal remains as well as from ancient archaeological samples. The present method has the advantages that it is quick with high yield, inexpensive, robust, environment friendly and does not require use of hazardous organic solvents.

A recurring problem in forensic medicine is the need to fix the time of death within the limits of probability. Errors in overestimating and underestimating the post-mortem interval based on body cooling is common. Post-mortem biochemistry has become a potent additional procedure in forensic death investigation. However, in our experiment, to determine the post-mortem interval we investigated the ATPase activity. The investigation was performed on the liver tissue of 25 corpses (21 men and four women) of age ranging between 40–60 years. The study of ATPase enzymatic activity shows that there is a considerable drop in the levels of ATPase activity with increasing post-mortem interval up to 24 h and this is one of the most reliable methods for estimating time of death.

We performed transcriptome sequencing of canine retinal tissue by 454 GS-FLX and Ion Torrent PGM platforms. RNA-Seq analysis by CLC Genomics Workbench mapped expression of 10,360 genes. Gene ontology analysis of retinal transcriptome revealed abundance of transcripts known to be involved in vision associated processes. The de novo assembly of the sequences using CAP3 generated 29,683 contigs with mean length of 560.9 and N50 of 619 bases. Further analysis of contigs predicted 3,827 full-length cDNAs and 29,481 (99%) open reading frames (ORFs). In addition, 3,782 contigs were assigned to 316 KEGG pathways which included melanogenesis, phototransduction, and retinol metabolism with 33, 15, and 11 contigs, respectively. Among the identified microsatellites, dinucleotide repeats were 68.84%, followed by trinucleotides, tetranucleotides, pentanucleotides, and hexanucleotides in proportions of 25.76, 9.40, 2.52, and 0.96%, respectively. This study will serve as a valuable resource for understanding the biology and function of canine retina.

Progressive retinal atrophy (PRA) is one of the major causes of retinal photoreceptor cell degeneration in canines. The inheritance pattern of PRA is autosomal recessive and genetically heterogeneous. Here, using targeted sequencing technology, we have performed exome sequencing of 10 PRA-affected (Spitz=7, Cocker Spaniel=1, Lhasa Aphso=1 and Spitz-Labrador cross breed=1) and 6 normal (Spitz=5, Cocker Spaniel=1) dogs. The high-throughput sequencing using 454-Roche Titanium sequencer generated about 2.16 Giga bases of raw data. Initially, we have successfully identified 25,619 single nucleotide polymorphisms (SNPs) that passed the stringent SNP calling parameters. Further, we performed association study on the cohort, and the highly significant (0.001) associations were short-listed and investigated in-depth. Out of the 171 significant SNPs, 113 were previously unreported. Interestingly, six among them were non-synonymous coding (NSC) SNPs, which includes CPPED1 A>G (p.M307V), PITRM1 T>G (p.S715A), APP G>A (p.T266M), RNF213 A>G (p.V1482A), C>A (p.V1456L), and SLC46A3 G>A (p.R168Q). On the other hand, 35 out of 113 unreported SNPs were falling in regulatory regions such as 3'-UTR, 5'-UTR, etc. In-depth bioinformatics analysis revealed that majority of NSC SNPs have damaging effect and alter protein stability. This study highlighted the genetic markers associated with PRA, which will help to develop genetic assay-based screening in effective breeding.

Lead (Pb) which plays a significant role in modern industry is related to a broad range of physiological, biochemical, behavioural and genetical dysfunctions. Its exposure leads to an increased frequency of genetic aberrations in humans. Hence, this study was designed to assess the genotoxic effect of lead acetate at three dosage levels (10, 25 and 50 µg/mL) by employing: the Cytokinesis Block Micronucleus (CBMN) assay and the Comet assay in Peripheral Blood Lymphocyte Cultures. The results of this study revealed an increased level of DNA damage among treated groups. A significant increase in the tail length of comets and other indices was observed at 25 and 50 µg/mL concentrations comparatively. Thus, lead acetate induced single-strand breaks (SSB) and double strand breaks (DSB) in DNA, alkali-labile sites (ALS), oxidative DNA damage as well as DNA-DNA/DNA-protein/DNA-metal cross linking as evidenced by the Comet assay. The chromosome breakage, DNA misrepair, chromosome loss and telomere end fusion were determined by the Micronucleus assay. Micronucleus frequency in treated lymphocytes was significantly higher as compared to controls. Nucleoplasmic bridges increased significantly and Nuclear buds increased at higher two doses only in exposed cultures. Thus, these assays are better indices for lead induced genotoxicity and metal-nucleus interactions.

Leiomyosarcoma (LMS) of the colo-rectum is a rare malignant entity with unfavourable prognosis, and responds poorly to conventional chemo-radiation therapy. Only a few cases of the LMS of colorectum have so far been reported earlier. Here we report two such cases of primary leiomyosarcoma of sigmoid colon and rectum. Due to histological similarity with gastrointestinal stromal tumour (GIST), the LMS cases were misdiagnosed as GIST. This is essentially a pathological diagnosis having a similar histomorphological appearance that of GIST, but a different Immunohistochemistry profile, in contrast to GIST. Immunohistocytochemically LMS are negative for CD34, CD117 and DOG1 and positive for desmin as detected in this report. GIST is curable with surgery followed by imatinib (in intermediate /high-risk patients) while LMS behaves aggressively requiring radical excision of the tumour followed by intensive cytotoxic chemotherapy regimens. Thus it is important to diagnose LMS definitively by immunohistochemical profiling as the prognosis and treatment of these tumours vary from others as mentioned.

A number of 2H-1,3-benzoxazin-4(3H)-one derivatives containing indole or benzofuran moieties were synthesized by using Pd/C-Cu mediated coupling-cyclization strategy as a key step. The o-iodoanilides or o-iodophenol were coupled with 3-{2-(prop-2-ynyloxy)ethyl}-2H-benzo[e][1,3]oxazin-4(3H)-one using 10%Pd/C-CuI-PPh3 as a catalyst system and Et3N as a base to give the target compounds. All the synthesized compounds were tested for their PDE4B inhibitory potential in vitro using a cell based cAMP reporter assay. Some of them showed fold increase of the cAMP level when tested at 30 μM. A representative compound showed encouraging PDE4B inhibitory properties that were supported by its docking results.

This work evaluates cationic intercalation of Capecitabine (Xeloda), an antineoplastic agent in interlayer gallery of Na + -MMT, which was further compounded with Poly ( L -Lactide) to form microcomposite spheres, for oral chemotherapy of breast cancer. The XRD, TGA, SEM, TEM and FT-IR analysis indicated the CAP intercalated in interlayer of MMT and stabilized in the longitudinal monolayer mode by electrostatic interface. No significant alteration in fundamental active properties of CAP was found in the MMT efficacy and data from in vitro study showed controlled drug release pattern >72 h. The efficacy of CAP-MMT hybrid/MPs was also confirmed on Human neuroblastoma cell line (IMR32) by in vitro cell culture experiments evaluating cell cytotoxic and oxidative stress marker indices which showed that intercalated drug and MPs, were as effective as pristine drug. In vivo pharmacokinetics of CAP-MMT hybrids in rats was examined and plasma CAP levels were evaluated. Our findings suggest that CAP-MMT hybrids and MPs can be of considerable value in chemotherapy of malignant neoplastic disease with reduced side effects and clearly demonstrated that MMT not only plays a role as a delivery matrix for drug but also facilitates significant increase in the delivery proficiency.

Lead, a heavy metal and multifaceted toxicant, is well studied for its distribution and toxicity in ecosystem, yet there is no consensus on its amelioration by any synthetic or phytochemical compounds. Curcumin, a known antioxidant and dietary element, is a well-known herb, for its therapeutic uses and having a wide spectrum of its beneficial properties against several adverse effects. Hence, the current study was taken into consideration to evaluate the ameliorative effects of curcumin (3.87 μM, i.e. 1.43 μg/ml) against lead acetate (doses: 10-6 M, i.e. 0.379 μg/ml and 10-4 M, i.e. 37.9 μg/ml, durations: 24 h and 69 h) induced genotoxicity and oxidative stress in human peripheral blood lymphocyte cultures (PBLC). On one hand, antigenotoxic and antioxidative potentials of curcumin against lead were simultaneously evaluated by the array of genotoxicity and oxidative stress indices. The result postulated that lead acetate showed dose- and duration-dependent increase in both genotoxicity and oxidative stress whereas curcumin, when added along with lead acetate, showed the significant amelioration in all genotoxic and oxidative stress-related indices. The study indicated that, due to alteration in antioxidant defense system, there is an adverse genotoxic effect of lead. On the other hand, curcumin, a potent antidote, can protect chromatin material against lead -mediated genotoxicity by balancing the activity of antioxidant defense system.

Lead (Pb) is present in the natural and occupational environment and it is one of the most clinically important heavy metals, because it induces a broad range of physiological, biochemical and genetical dys- functions. Its exposure leads to an increased frequency of genetic aberrations in human beings. Hence, this investigation was conducted to assess the genotoxic effect of lead at three dosage levels. In the present study, the DNA damage was detected by adopting the alkaline single cell gel electrophoresis assay (Comet Assay) in peripheral blood lymphocyte cultures. The result of this study revealed an increased level of DNA damage among treated groups. A significant increase in the tail length of comets and other indices was observed at 25 µg/ml and 50 µg/ml concentrations comparatively. Thus lead acetate induced single- strand breaks (SSB) and double strand breaks (DSB) in DNA, alkali-labile sites (ALS), oxidative DNA damage as well as DNA-DNA / DNA-protein / DNA-metal cross linking as evidenced by the comet assay.

Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants and overproduction or incorporation of free radicals from environment to living systems leads to serious damage. It also attacks nervous system resulting in neural-degeneration. In order to evaluate the neurotoxic effect on the brain parts of mercury in our study, oxidative stress indices of enzymatic and non enzymatic components were measured in rats intoxicated with mercury (2 mg and 4 mg/kg body weight) for 60 days to adult rats. Along with gravimetry, tissue burden was also recorded. Alterations in these indices were further supported by ultrastructural studies carried out in the brain as indicated by myelin disintegration, cell organelle alterations and neuronal loss by mercury poisoning. Treatment with the antioxidant melatonin (N-acetyl 5-methoxy tryptamine, 5 mg/kg) prevented mercury exerted toxicity due to its antioxidant property. The pathological changes were also ameliorated in the brain region comparatively to support biochemical profile of brain. Thus, melatonin produced neuroprotection against mercury poisoning in rats.

The present study was aimed to evaluate curcumin as a potential natural antioxidant to mitigate the genotoxic effects of arsenic (As) and fluoride (F) in human peripheral blood lymphocytes. The study was divided into nine groups consisting of negative control, positive control treated with ethyl methane sulphonate (EMS; 1.93 mM) and curcumin control with only curcumin (1.7 microM) in blood culture. As (1.4 microM) and F (34 microM) were added alone as well as in combination, to the cultures, with and without curcumin. Cultures were analysed for chromosomal aberrations (both structural and numerical) and primary DNA damage via comet assay as the genotoxic parameters after an exposure duration of 24h. Results revealed that curcumin efficiently ameliorates the toxic effect of As and F by reducing the frequency of structural aberrations (60%), hypoploidy (50%) and primary DNA damage. In conclusion, curcumin mitigates the genotoxic effects of the two well known water contaminants (As and F) effectively and efficiently at the given concentration in vitro.

The effect of melatonin on the neurotoxicity induced by mercuric chloride was studied. Adult rats were fed orally with two different doses of mercuric chloride (2 mg; 4 mg/kg body weight) to evaluate brain toxicity with respect to cerebral hemisphere, cerebellum, and medulla oblongata regions for 60 days with or without supplementation with melatonin (5 mg/kg body weight) intraperitoneally. The results suggest that the graded doses of mercury elicit the depletion of enzymatic activities, such as adenosine triphosphatase, succinate dehydrogenase, phosphorylase, alkaline phosphatase, acid phosphatase, altered glycogen, total protein, and lipid peroxidation levels in the cerebral hemisphere, cerebellum, and medulla oblongata of the brain, thereby affecting their respective functions. Blood glucose and mercury levels increased, followed by a reduction in body and organ weights. All these effects seemed to be severe in the cerebral hemisphere of the brain. Further affected indices were, to some extent, maintained in the brain of animals cotreated with melatonin, showing its protective role against mercury-exerted neurotoxicity.

Present study investigated the protective role of melatonin (MLT, 5 mg/kg body wt., ip) against the long term effects of mercuric chloride (MC; 2 and 4 mg/kg body wt., po) in the thyroid gland of the rats through certain antioxidative indices like superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione (GSH), catalase (CAT) and lipid peroxidation (LPO), other biochemical parameters such as succinate dehydrogenase (SDH), adenosine triphosphatase (ATPase), acid phosphatase (ACPase) and alkaline phosphatase (ALPase) were also measured. Antioxidative enzymes and other parameters showed a significant reduction while LPO and mercury levels increased significantly in a dose dependent manner in MC treated animals as compared to control groups. Co-treatment with MLT revealed no significant effect on antioxidative and metabolic indices in the thyroid gland of rats. The results of present study thus strongly suggest that mercury affected antioxidant defense system and other metabolic enzymes of thyroid. Co-administration of melatonin exerted a protective effect against mercury induced endocrine toxicity.

A novel water-soluble [60] fullerene-substituted lysine derivative 3 has been synthesized and characterized by elemental analysis, 1H NMR, 13C NMR and FAB-MS. The synthetic procedure involved condensation of Boc-protected lysine with terephthaldehyde followed by 1,3-dipolar cycloaddition reaction with C60 in the presence of sarcosine and finally deprotection of the amino group using trifluoroacetic acid. The synthesized compound 3 exhibited high DNA cleavage efficiency upon visible light irradiation in the presence of NADH.

Ground water contamination of arsenic in drinking water is a burning problem worldwide; especially in West Bengal (India) and Bangladesh. The main endeavor in this study was to assess the role of vitamin A (2.72 μM/7 ml culture), a naturally occurring antioxidant upon arsenic-induced genotoxicity; with respect to chromosomal aberrations (structural and numerical) and micronuclei. Whole blood cultures set for 72 h were exposed to test chemicals for a period of 24 h ahead of harvesting. Arsenic concentrations tested in the present study are 0.36, 0.72 and 1.4 μM/7 ml culture. Mitomycin C (MMC), the direct acting mutagen was used as positive control. Our data indicates that at concentrations tested, arsenic-induced increase in the mean frequencies of these genotoxic indices were diminished by vitamin A, indicating its protective role towards cells from arsenic exerted injury.

This study was undertaken to determine whether vitamin A (vit. A), which was shown to possess antioxidant properties when co-administered with arsenic trioxide (As2 O3) might prevent As-induced detrimental effects. Two doses of As (0.5 or 1 mg kg−1 body weight), alone and in combination with vit. A as retinyl palmitate (0.2 mg kg−1 body weight), were used in this study. Parameters assessed included acetyl cholinesterase (AChE) activity and levels of total proteins, cholesterol and total lipids in cerebral hemisphere (CH) and cerebellum (C) regions of the brain as well as the serum of mice. Significant decreases in AChE activity and levels of proteins together with other parameters were noted in the brain and blood. These effects were significantly mitigated by co-treatment with vit. A. These results emphasize that concurrent supplementation of vit. A significantly protects against As-induced toxicity.

KEYWORDS Acrocentric association; telomeric association; C-anaphase; nickel; chromium; curcumin; blood cultures ABSTRACT Tanners, welders and workers in various industries are exposed to acute and chronic toxicity of these heavy metals world wide. The present work is undertaken to evaluate the genotoxic effects of Ni and Cr at two different exposure intervals with a single dose and the amelioration of this toxicity using curcumin. Ni in form of nickel chloride (4.216 X 10 -5 M) and Cr as potassium dichromate (1.36 X 10 -6 M) were exposed for 24 and 69 hours to human blood lymphocyte cultures. The genotoxicity was measured by changes in acrocentric and telomeric association and C-anaphase. Results revealed a significant positive correlation between DNA damage and exposure time in Ni and Cr added cultures alone. Likewise it was also observed in cultures with combination of both pro-oxidants. Groups supplemented with curcumin (3.87 X 10 -7 M) showed insignificant cytogenetic damage indicating its protective role which was calculated as percentage amelioration. Thus these data proved curcumin as a protective agent against Ni and Cr induced genotoxicity.

The effects of oral administration of sodium fluoride (NaF) and/or arsenic trioxide (As(2)O(3)) (5 mg and 0.5 mg/kg body weight, respectively) for 30 days were investigated on free radical induced toxicity in the mouse ovary. The reversibility of the induced effects after withdrawal of NaF+As(2)O(3) treatment and by administration of antioxidant vitamins (C, E) and calcium alone as well as in combination were also studied. The combined treatment of NaF and As(2)O(3) impaired significantly (p0.001) the production of free radical scavengers such as glutathione and ascorbic acid as well as antioxidant enzymes, namely, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (Cat), thereby increasing ovarian lipid peroxides (LPO) which might have rendered the ovary susceptible to injury. The withdrawal of the combined (NaF and As(2)O(3) for 30 days) treatment caused partial recovery in the ovary, which was more pronounced (p0.001) by treatment with vitamin C, calcium, or vitamin E alone and in combination. Hence the induced toxicity was transient and reversible.

In vitro effects of arsenic in human peripheral lymphocytes (HPL) at three different doses – 3.6×10 −4 , 1.4×10 −3 and 0.72×10 −3 μM for 24 h before harvesting on sister chromatid exchanges (SCE), Cell cycle proliferative index/replicative index (CCPI/RI), % M 1 , % M 2 and % M 3 , population doubling time (PDT) and average generation time (AGT) were examined. Andrographis paniculata (commonly referred to as ‘kalmegh’) has been used for centuries in traditional Indian and Chinese herbal medicine as a safe, natural folk remedy for assorted health concerns. In the present study, kalmegh (0.01 μg/7 ml culture media) was used along with the highest dose of arsenic; the results showed that arsenic induced increase in these genotoxic endpoints were fairly diminished by kalmegh. In addition, mutagenic in vitro effect of ethyl methanesulphonate (EMS) was used as a positive control in this study. It is thus concluded from this study that Andrographis has a protective role in arsenic toxicity.

Arsenic effect was studied at two dosage levels (0.5 mg and 1 mg/kg) for 45 days in two regions of brain, viz., cerebral hemisphere (CH) and cerebellum (C) in adult mice. This study included the antioxidant profile namely superoxide dismutase (SOD), catalase, lipid peroxidation, reduced glutathione, ascorbic acid and total sulphydryl groups. Adenosine triphosphatase (ATPase), succinic dehydrogenase (SDH), phosphorylase together with glycogen and protein levels were also estimated as metabolic indices in the brain regions of mice. A notable decrease was detected in the activities of the enzymes and in the levels of other metabolites together with a significant increase in the lipid peroxidation, glycogen and inorganic arsenic levels after arsenic administration. Supplementation of vitamin A to the arsenic treated mice brought about no significant variation in these antioxidant and metabolic indices in comparison to that of control, revealing amelioration by vitamin A on arsenic exerted metabolic and neurotoxic effects in mice.

Objective: The compound, 2,4-dichlorophenoxyacetic acid (2,4-D), is a systemic phenoxy herbicide and a plant growth regulator. Histopathological effects of 2,4-D alone and in combination with melatonin on the kidney in adult albino male mice of the Swiss strain were evaluated in the present study.Methods: Twenty adult male albino mice weighing between 30 and 40 g were assigned into four groups with five mice in each group. Group I served as control; Group II - melatonin alone (10 mg/kg body weight); Group III - 2,4-D alone (50 mg/kg body weight); and Group IV - 2,4-D + melatonin was given orally for 45 days.Results: It revealed a significant reduction in the body and kidney weights (p

Sodium fluoride (NaF) at a dose of 10 mg/kg body weight was administered orally to female rats daily for 30 days to evaluate its affect on thyroid functions in relation to oxidative stress in rats. The parameters studied were gravimetric and biochemical indices in endocrine tissue of fluoride fed rats. Treatment brought about an alteration in body and organ weights followed by biochemical indices. Alterations in the antioxidant indices in the thyroid tissue were confirmed by increased lipid peroxidation (LPO) along with decrements in other antioxidant indices such as superoxide dismutase (SOD) and catalase (CAT) levels affecting its internal milieu in fluoride intoxicated rats. Thyroid hormone levels Tri-iodothyronine (T3), Thyroxine (T4) and TSH were also affected. Supplementation of antioxidant, triphala (30 mg/kg body weight) to treated animals, revealed recovery in these endocrine organ functions due to its probable protective role. Thus, triphala mitigated NaF induced endocrine toxicity in a rat model, as it has good antioxidant properties.

Various antioxidants play an important role in reducing the reactive oxygen species (ROS) by scavenging them directly or indirectly. Mercury (Hg) is one of the known hazardous genotoxicant, induces the genotoxicity by enhancing the ROS. In the present study, three structurally different bioactive compounds such as melatonin (0.2 mM), curcumin (3.87 µM) and andrographolide (0.4 µM) were evaluated against the genotoxic effect of mercury. All the experiments were conducted using the peripheral blood lymphocytes In Vitro. The cultures were exposed to different doses (2.63 µM; 6.57 µM; 10.52 µM) of mercury salt (HgCl2) for studying various genotoxic indices. All three antioxidant compounds, alone and in combination with high dose of mercury, were added to the cultures with controls. For ascertaining genotoxicity, sister chromatid exchanges (SCEs), cell cycle proliferative index/replicative index (CCPI/RI), average generation time (AGT), population doubling time (PDT), %M1, %M2 and %M3 were assessed and analyzed using suitable statistical analysis. The results revealed a dose dependent increase in SCEs, AGT and PDT, with a concomitant reduction in CCPI values after treatment of mercury. Supplementation of these three antioxidant compounds effectively negated these genotoxic endpoints in treated cultures with improvement in the cell cycle kinetics i.e. CCPI. The antimutagenic activity of these compounds on mercury induced genotoxicity was in the following order: melatonin curcumin andrographolide. In conclusion, these compounds have ameliorated mercury induced increase in genotoxic indices due to their excellent antioxidant properties and the combination seems to be effective.

Curcumin, the yellow pigment in turmeric, is present in the rhizomes of the plant Curcuma longa. Mercury (HgCl2) induces various toxic effects in different organs of the body. The present work was undertaken to evaluate the beneficial effect of curcumin following mercuric chloride induced oxidative stress in rat brain. The antioxidative indices assayed were superoxide dismutase, glutathione peroxidase, glutathione reductase, thiobarbituric acidreactive substances and total –SH groups. Metabolic parameters like total protein, cholesterol, succinate dehydrogenase, adenosine triphosphatase and mercury levels were also measured. Mercury exposure resulted in a significant increase in thiobarbituric acid-reactive substances and mercury levels. Contrarily a decrease in the activities of most of those enzymes, total –SH groups, protein and cholesterol levels were noted. Curcumin administration reduced TBARS and mercury levels, whereas it enhanced the other enzyme activities, total –SH groups, proteins and cholesterol levels comparable to controls. In summary, curcumin administration protects different parts of the brain against mercuric chloride induced neurotoxicity. Introduction Mercury is released into the environment through various natural geological processes, such as volatilization of rocks, dissolution, and volcanic eruption as well as due to some anthropogenic activities like combustion of fossil fuels, incineration of waste, mining and industrial discharge (Agrawal and Baheri, 2007). The cellular mechanisms by which mercury compounds exert their neurotoxic action were obtained from in vitro studies. Sorg et al. (1998) proposed that the mechanism of mercury toxicity could be via binding to thiol groups. Mercury compounds can inactivate a number of enzymes by blocking the functional sites binding to -SH groups, which are part of the catalytic or binding domains. Mercury treatment induced the dramatic increase in reactive oxygen species accumulating in rat brain cell cultures, leading to increased lipid peroxidation, protein degradation, and finally to cell death (Sorg et al., 1998). Rats and mice injected with inorganic mercury were detected with mercury granules in the different regions of the nervous system (Neustadt and Pieczenik, 2007). Mercury treatment exerted significant increase in ROS only in the cortical region and marked dose dependent increase (2500-5600-fold) in total Hg in the different brain regions (Goering et al., 2002). Morphological changes and Hg accumulation are different between cerebral hemisphere and cerebellar astrocytes after mercury treatment cultured from newborn rats (Adachi and Kunimoto, 2005). Pregnant female rats exposed to a very low dose of inorganic mercury from prenatal day 0 continued to postnatal day 20, the highest Hg content was present in the infant hippocampus and cerebellum, whereas its content in maternal brain regions like cerebrum, cerebellum, brain stem, hippocampus and thalamus (Feng et al., 2004). However, the role of herbal antioxidants on metal exerted neurotoxicity is attained less attention. Hence, this study was proposed to investigate the ameliorative effect of curcumin powder on regional brain toxicity induced by mercury in the rat. Rao et al. (2009) also studied effects of Hg in different regions of male rat brain affecting it in a dose dependent manner and role of melatonin on its toxicity. Materials and Methods Male Wistar strain Albino rats (Rattus norvegicus), weighing 200-250gms were procured from Cadila Pharma, under the Animal maintenance and Registration No.167/1999/CPCSEA from the ministry of Social Justice and empowerment, Govt. of India. The rats were fed on the standard commercial laboratory chow and distilled water ad libitum and were housed in the plastic cages with good ventilation. Light dark conditions as well as temperature was maintained (12h: 12h and 26±2oC respectively) throughout the seasons. Animals were assigned to 5 groups of 8 rats each. Group I served as control and animals were provided with distilled water. Group II animals received (low dose) HgCl2 (2mg/kg body weight) orally. Group III was administered with 4 mg/kg body weight (high dose) of mercuric chloride. Group IV received curcumin alone (80mg/kg body weight) and Group V received curcumin along with high dose of HgCl2. All the treatments were administered for 2 months and on the 61st day the animals were weighed and necropsy was performed. The brain was dissected carefully and weighed. Experiments were carried out on cerebral hemisphere and cerebellum. Antioxidant parameters The antioxidant enzyme activities like superoxide dismutase (SOD, EC:1.15.1.1), glutathione reductase (GR, EC:1.6.4.2), glutathione peroxidase (GPx, EC:1.11.1.9) were analysed by the spectrophotometric method of Kakkar et al. (1984), modified method of Pagila and Valentine (1967) and the method of Carlberg and Mannervik (1985) respectively. Thiobarbituric acid-reactive substances (TBARS) were determined by Ohkawa et al., (1979). Biochemical parameters The methods of total (-SH), succinate dehydrogenase (SDH, EC:1.3.99.1) and adenosine triphosphatase (ATPase, EC:3.6.1.3) was carried out by the methods of Sedlak and Lindsey (1968), Beatty et.al., (1966) and Quinn and White (1968) respectively. Total proteins and Cholesterol were determined by the methods of Lowry et al., (1951) and Zlatkis et. al., (1953) respectively. Mercury levels in the brain were estimated using mercury analyzer (MA 5840, Electronic Corporation of India Ltd., Hyderabad) using acid digestion method followed by cold vaporization of the sample. Data were statistically analyzed by Student’s t-test and ANOVA. Results Antioxidant system. In the present study antioxidant enzymes such as SOD, GPx, and GR were significantly (P

Healthy adult female rats (Rattus norvegicus) were administered sodium fluoride (NaF) at the dose of 10 mg/ kg body weight and triphala at 30 mg/kg body weight orally. Both doses were given individually and also in combination for 30 days to investigate the fluoride toxicity in blood and its reversal by triphala. NaF feeding also brought about a significant decline in hemoglobin level, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) and red blood cell (RBC), which suggested occurrence of anemia and probable effect on haemopoetic system. Significant increase in erythrocyte sedimentation rate (ESR) indicates toxic effects in the body. Increase in white blood cells (WBC) count significantly suggests adverse effect of NaF treatment on the immune system of the rats. Co-administration of triphala to fluoride treated rats resulted in a partial effects in blood and body weight due to its probable protective role. Thus, triphala mitigated NaF induced toxicity marginally in a rat model. INTRODUCTION Fluorine is one of the most active elements, which belong to halogen group with a atomic number 9. The mass number of its isotopes are 18 and 19 but only the natural isotope 19F is stable.1 Fluoride (F-) in water sources is known to induce both useful and harmful influences on human body. Excessive amount of F can cause fluorosis.2 It is one of the most electronegative ions commonly used in the pharmaceutical and agrochemical industries.3 Fluoride intoxication causes different disorders in the body including hepatotoxicity, nephrotoxicity, neurotoxicity, and cardiotoxicity,3,4 associated with oxidative stress and altered anti-oxidant defense mechanisms. Previous studies from our laboratories and others have indicated that, consumption of antioxidant, such as Triphala, may mitigate the fluoride-induced oxidative stress in different tissues of rats.5 It also appears to be beneficial in its free-radical scavenging actions beyond its stimulatory effects on antioxidant enzyme system.6,7 The current study was undertaken to scrutinize mitigative role of Triphala on fluoride induced blood toxicity. METHODS AND MATERIALS Animals: Mature female Wistar rats (Rattus norvegicus) weighing between 250 and 350gm were procured from ZydusCadila Health Care, Ahmedabad under the Animal Maintenance and Registration No. 167/PO/C/99/CPCSEA from the Ministry of Social Justice and Empowerment, Government of India. The animals were housed under standard temperature (24±1oC) at a 12-hr dark/light cycle. They were fed standard rodent food (Pranav Agro Industries, Vadodara, India) and water ad libitum. Experimental design: After a 15-day adaptation period, the animals were divided into five different groups (Table 1) of 15 each and caged separately. Based on our earlier studies,1 the following doses were given for 30 days. Group I (control) rats were maintained on standard diet. Group II was treated with Triphala alone (30mg/kg bw) orally. Group III was administered a dose of sodium fluoride (10mg/kg bw) orally. Group IV was given 10 mg/kg bw dose of NaF along with Triphala 30mg/kg bw orally. After 30 days, the rats were fasted overnight and sacrificed under mild ether anesthesia. The weight of the body were recorded, and blood was colored by cardiac puncture and it was allowed to clot for 1 hour at room temperature and thereafter serum was separated by centrifugation and used for various serum parameters. Table 1. Experimental Protocol Group Treatment and daily dose (15 rats in each group) Duration

This study was conducted to investigate effects of sodium fluoride (NaF) on brain (cerebral hemisphere) of rat and its possible amelioration by melatonin. Adult male Wistar rats (Rattus novergicus) were administered sodium fluoride (NaF) at the doses of 5 and 10 mg/kg body weight and melatonin 10 mg/kg body weight for 60 days. Gravimetric and biochemical indices were done of brain an also studied. The increased lipid peroxidation (LPO) indicated an oxidative stress and the elevated fluoride levels in brain tissue could be the result of the inhibition of antioxidant enzymes (SOD, CAT) in the brain region of rats fed with fluoride. These changes were correlated with accumulation of fluoride in the region. However, these effects were ameliorated by co-supplementation of melatonin along with NaF in rats, because of its antioxidant cascade phenomenon. INTRODUCTION The presence of fluorine in ground water is mainly a natural phenomenon and influenced by local and regional conditions.1 Intake of high levels of fluoride is known to cause structural deformities, altered activities of enzymes, and metabolic lesions in the brain of experimental animals. Fluorosis exhibits neurological problems such as a tingling sensation in the fingers and toes, nervousness and depression. In the advanced stages of fluorosis, neurological manifestations such as paralysis of the limbs, vertigo, spasticity in the extremities, and impaired mental acuity, are observed in human beings.2 Sharma et al.3 reported that inhabitants of certain villages in Sanganer Tehsil, Jaipur, India were found to be suffering from various neurological disorders due to high levels of Fin the ground water; the main neurological manifestations observed were headache, insomnia, lethargy, depression, polyuria and polydipsia. Effects of NaF on the expression of intracellular Ca2+ fluxes, apoptosis and the antagonism of taurine in murine neuron were reported.4,5 Melatonin is a methoxyindole synthesized within the pineal gland. The hormone has strong antioxidant action neurodegenerative disorders.6 Therefore, to test this hypothesis, the present study was designed to investigate the role of melatonin administration in fluoride induced neurotoxicity in rats. MATERIALS AND METHODS Animals: Mature male Wistar rats (Rattus norvegicus) weighing between 200 and 300gm were procured from ZydusCadila Health Care, Ahmedabad under the Animal Maintenance and Registration No. 167/PO/c/99/CPCSEA from the Ministry of Social Justice and Empowerment, Government of India. The animals were housed under standard temperature (24±1oC) at a 12-hr dark/light cycle. They were fed standard rodent food (Pranav Agro Industries, Vadodara, India) and water ad libitum. Experimental protocol: After 15 days adaptation period, the animals were divided into five different groups (Table 1) of 15 each and caged separately. Based on our earlier studies,7 the following doses were given to rats for 60 days. After 60 days, the rats were fasted overnight and sacrificed under mild ether anesthesia. The weight of cerebral hemisphere was recorded, and the tissue was utilized for the estimation of different biochemical parameters. Table 1. Experimental Protocol Group Treatment and daily dose (15 rats in each group) Duration (days) Day of autopsy I Untreated (control) Sacrificed with treated

The title compounds (III) are obtained via a two-step one-pot synthesis involving the construction of the cyclohexanone ring from aromatic aldehydes and β-ketoesters as initial step under mild reaction conditions.