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1.
Neurotoxicology ; 99: 139-151, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37865141

ABSTRACT

It is widely reported now that nanoplastic particles have potential neurotoxic effects and may disturb central nervous system (CNS) function. However, the mechanism behind these toxic effects still needs to be elucidated. In the current study, we investigated the effects of polystyrene nanoplastics (PS-NPs) on changes in learning, memory, and anxiety-related behavior in mice based on some selected biochemical, molecular, and histopathological changes in three important brain regions (Cortex, Hypothalamus, and Hippocampus). Male mice were orally administered daily with two doses of 50 nm PS-NPs (0.2 mg/ml and 1 mg/ml) for 8 weeks. We observed decreased expression of neurotransmitter-related genes (VAChT, GAD, and SYP) in the cortex, hypothalamus, and hippocampus areas of the mouse brain. Other biochemical variables including, antioxidant enzymes, biomarkers for oxidative stress, and acetylcholinesterase activity showed significant alterations in all three brain regions. Molecular and neurochemical data thus suggest significant neurobehavioral changes following sub-chronic exposure to PS-NPs which may lead to enhanced anxiety-related and spatial learning and memory-related impairments by affecting limbic areas of the brain.


Subject(s)
Nanoparticles , Water Pollutants, Chemical , Male , Mice , Animals , Polystyrenes/toxicity , Polystyrenes/metabolism , Acetylcholinesterase/metabolism , Brain/metabolism , Oxidative Stress , Anxiety/chemically induced , Memory Disorders/metabolism , Nanoparticles/chemistry , Water Pollutants, Chemical/toxicity
2.
Xenobiotica ; 53(4): 320-331, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37449383

ABSTRACT

This study explores the effects of prenatal and postnatal (until weaning period) arsenic exposure given via pregnant females on Wistar rat neonates. Pregnant female rats were divided in four groups - control, low dose, moderate dose and high dose groups of sodium arsenite exposure during gestation and weaning period. Half of the neonates were sacrificed at day 1 of birth and other half at day 21 of birth. Cell cycle analysis in epidermal keratinocytes using flowcytometer revealed that there was a consistent increase in number of cells in G2/M phase from 0.04% in control group to 0.88%, 1.59% and 2.77% in low, moderate and high dose groups respectively for neonates sacrificed at day-1. Whereas, the increase in number of cells with increasing doses in G2/M phase of neonates sacrificed at day-21 was from 3.44% to 5.1%, 6.82%, and 9.17%. At postnatal day 21, mRNA expression of Cyclin A and B1, p53, Caspases 3, 7 and 9, and Bax were found to be up-regulated. Whereas that of Cyclin E, CDK 1 and 2 and Bcl2 were down regulated consistently in skin tissues of arsenic exposed groups.


Subject(s)
Arsenic , Pregnancy , Rats , Female , Animals , Arsenic/toxicity , Rats, Wistar , Skin , Cell Cycle , Cell Division
3.
Andrologia ; 54(11): e14631, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36344280

ABSTRACT

Iron oxide nanoparticles (IONP) are being utilised for various biomedical applications due to their unique properties like superparamagnetism and greater colloidal stability. Interaction of IONP with male reproductive system is underrepresented in the literature. Current study strives to demonstrate the effects of IONP on sperm quality, reproductive hormones and fertility of adult Wistar rats. Spherical IONP with 15-20 nm size were injected for a maximum of 60 days in three different exposure schemes. Three increasing doses (20, 40 and 80 mg/kg) along with a control group were tested. Sperm count, sperm viability, motility and morphology were scored after the experimental periods. A group of rats was used to examine male fertility. Concentrations of male reproductive hormones in serum were also measured in all groups. Total sperm count and motility was significantly decreased in treated groups in comparison to control after 60 days of exposure. Changes in sperm viability and sperm morphology mostly proved to be statistically insignificant. Serum concentrations reproductive hormones like testosterone, luteinizing hormone and follicular stimulating hormone varied insignificantly between control and treatment groups. Male fertility was also not affected due to the exposure. Further, it is also reported that a 45-day recovery period restores the sperm quality up to a considerable extent. Overall, the study demonstrates that long term exposure of IONP has adverse effects on male sperm production and function that can be reversed if exposure is withdrawn.


Subject(s)
Sperm Motility , Testis , Male , Rats , Animals , Rats, Wistar , Sperm Count , Semen , Spermatozoa , Luteinizing Hormone , Follicle Stimulating Hormone , Testosterone , Fertility , Magnetic Iron Oxide Nanoparticles
4.
Toxicol Ind Health ; 37(12): 763-775, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34797179

ABSTRACT

Nanoparticles of iron oxide, with diameters beteween 1 to 100 nm, have notable implications for human health and well being. In the current study, we have investigated the effects of iron oxide nanoparticles (IONP) exposure on general physiology and health of adult Wistar rats. IONP used in the study had spherical shape and average size in the range of 15-20 nm. A total of eight groups of rats were repeatedly injected with 0 (control), 20, 40, and 80 mg IONP per kg body weight intraperitoneally under two different exposure schemes (sub-acute and sub-chronic). IONP exposure caused significant changes in lungs, liver, and kidney indices in both exposure schemes. Sub-acute exposure did not affect body weight gain in treated rats, but longer duration exposure was responsible for significant reduction in body weight. Mesenteries, visceral fatty tissues, and visceral peritoneal membranes demonstrated apparent accumulations of IONP in a dose and time-dependent manner. Hematological analysis showed that total RBC count, hemoglobin content, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and mean platelet volume (MPV) were not affected by IONP exposure. Total lymphocyte count, however, was elevated in low- and mid-dose treated rats, but not in high-dose group. Serum lactate dehydrogenase (LDH) increased significantly in rats treated with mid and high doses as compared to control. Serum creatinine and blood urea nitrogen levels were also significantly altered in treated rats. Histological study found significant hepatic damage and mild spleen toxicity. Our report suggests that IONP exhibit significant toxicity in rats.


Subject(s)
Ferric Compounds/toxicity , Nanoparticles/toxicity , Animals , Blood Urea Nitrogen , Creatinine/blood , Dose-Response Relationship, Drug , L-Lactate Dehydrogenase/blood , Liver/pathology , Male , Rats, Wistar , Spleen/pathology
5.
Toxicol Ind Health ; 37(2): 68-76, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33325330

ABSTRACT

In this study, the cytotoxic potential of fluoride and endosulfan in combination was investigated in Swiss albino mice bone marrow cells using the chromosomal aberration (CA) and micronucleus (MN) test systems. Fluoride (25.1 mg kg-1 body weight [bw] in water) and endosulfan (1.8 mg kg-1 bw by oral intubation) were administered orally alone and in combination (fluoride 25.1 mg kg-1 bw + endosulfan 1.8 mg kg-1 bw) to male Swiss albino mice daily for 30 days. A significant (p < 0.01) increase in micronuclei (MNs) induction and decreased ratio (p < 0.01) of polychromatic to normonochromatic erythrocytes (indicators of cytotoxicity) were observed compared with saline controls when animals were given the combination of fluoride and endosulfan. A significant (p < 0.01) increase in MNs induction and no change in the polychromatic erythrocytes to erythrocyte ratio were also observed when endosulfan was given alone. CAs such as gaps, breaks, fragments, rings, exchanges, and polyploidy were recorded in the bone marrow cells. The mean percent frequency of CAs was increased (p < 0.01) in all the treated groups compared with the control saline group. In the combination group (F + E), the percent frequencies of CAs were significantly higher (13.875%) compared with those in the individual treatment groups of fluoride (4.375%) and endosulfan (6.25%). The mitotic index was calculated as percentage of dividing cells. A significant (p < 0.01) decrease in mitotic index was observed in all treated groups compared with controls. In the combination group (F + E), mitotic index was significantly less than (p < 0.01; 4.1 ± 0.49) the saline control (10.8 ± 0.98). These results indicated that repeated intake of endosulfan through various sources in fluoride affected areas resulted in increased cytotoxic effects. The greater effect in the combination group indicated additive interaction of fluoride and endosulfan in inducing cytotoxicity in Swiss albino mice.


Subject(s)
Bone Marrow Cells , Endosulfan/toxicity , Fluorides/toxicity , Animals , Body Weight/drug effects , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Cells, Cultured , Chromosome Aberrations/drug effects , Male , Mice , Micronucleus Tests , Pesticides/toxicity
6.
Environ Sci Pollut Res Int ; 28(34): 46367-46376, 2021 Sep.
Article in English | MEDLINE | ID: mdl-32632678

ABSTRACT

Graphene oxide (GO) has a multitude of applications in areas of nanomedicine, electronics, textile, water purification, and catalysis among others. GO is relatively easier to manufacture and customize as compared with other carbon-based nanomaterials. In the present work, GO was administered intraperitoneally to adult Wistar rats in four incremental doses, i.e., 0.0 mg/kg (control), 0.4 mg/kg (low dose), 2.0 mg/kg (mid-dose), and 10.0 mg/kg (high dose). After 15 repeated doses over a period of 30 days, biochemical assays for alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), catalase (CAT), and malondialdehyde (MDA) were carried out. Histopathological and morphometric analyses of liver and kidney were also performed. Results demonstrated dose-dependent toxicity of GO. General behavior and liver indices remained unaffected in the study. Serum levels of ALT, ALP, and AST were altered significantly in high-dose treated animals. Changes were found insignificant in the low- and mid-dose groups. Catalase activity in liver tissue homogenates was decreased in the high-dose group. MDA levels were found elevated in treated rats. Unlike control and low dose, mid- and high-dose treated rats exhibited varying degrees of histopathological changes like inflammation around the central vein and portal veins, vacuolations, hepatocytic injury, and near normal to abnormal hepatic sinusoids. These findings show that GO has considerable toxic potential to mammalian liver and thorough toxicity studies are needed before these nanosheets are used in biomedicine.


Subject(s)
Chemical and Drug Induced Liver Injury , Graphite/toxicity , Liver , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Liver/drug effects , Liver/metabolism , Oxidative Stress , Rats , Rats, Wistar
7.
Basic Clin Pharmacol Toxicol ; 121(3): 202-210, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28371123

ABSTRACT

Nanoscale graphene oxide (NGO) has great potential in biomedicine by the virtue of its facile functionalization and tunable characteristics. Toxicity assessments have therefore become essential prior to its biomedical applications. This study examined the effects of NGO exposure on male reproductive function of adult Wistar rats. Rats were exposed intraperitoneally to three increasing doses, namely low-dose (0.4 mg/kg BW), mid-dose (2.0 mg/kg BW) and high-dose (10.0 mg/kg BW) of NGO. Repeated exposure of NGO for 15 and 30 days resulted in decreased epididymal sperm counts and elevated sperm abnormalities. Percentage of motile sperms was also significantly reduced due to the exposure. Activities of SOD, GPx and malondialdehyde concentration in the testes increased in a dose-specific manner. Results of the study demonstrated that high-dose of NGO resulted in considerable histological damage to testicular tissue which included atrophy of seminiferous tubules with reduction in germinal epithelium, germ cell loss and vacuolization. Low and mid-doses of NGO were not associated with sperm dysfunction or testis damage. Withdrawal of treatment for 30 days demonstrated significant recovery potential. Histology of epididymis and male fertility potential were not affected due to the NGO exposure. These findings are important for assessment of the risk involved in manufacturing, use and processing of the graphene oxide-based materials towards male reproductive function.


Subject(s)
Environmental Pollutants/toxicity , Epididymis/drug effects , Graphite/toxicity , Infertility, Male/chemically induced , Nanostructures/toxicity , Oxidative Stress/drug effects , Testis/drug effects , Animals , Biomarkers/metabolism , Dose-Response Relationship, Drug , Environmental Pollutants/administration & dosage , Environmental Pollutants/chemistry , Epididymis/metabolism , Epididymis/pathology , Graphite/administration & dosage , Graphite/chemistry , Infertility, Male/metabolism , Infertility, Male/pathology , Injections, Intraperitoneal , Male , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Nanostructures/administration & dosage , Nanostructures/chemistry , Nanostructures/ultrastructure , Oxidoreductases/metabolism , Rats, Wistar , Sperm Motility/drug effects , Spermatogenesis/drug effects , Spermatozoa/drug effects , Spermatozoa/metabolism , Spermatozoa/pathology , Testis/metabolism , Testis/pathology , Toxicity Tests, Subchronic
8.
Indian J Clin Biochem ; 28(4): 314-28, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24426232

ABSTRACT

The recognition of vitamin C is associated with a history of an unrelenting search for the cause of the ancient haemorrhagic disease scurvy. Isolated in 1928, vitamin C is essential for the development and maintenance of connective tissues. It plays an important role in bone formation, wound healing and the maintenance of healthy gums. Vitamin C plays an important role in a number of metabolic functions including the activation of the B vitamin, folic acid, the conversion of cholesterol to bile acids and the conversion of the amino acid, tryptophan, to the neurotransmitter, serotonin. It is an antioxidant that protects body from free radical damage. It is used as therapeutic agent in many diseases and disorders. Vitamin C protects the immune system, reduces the severity of allergic reactions and helps to fight off infections. However the significance and beneficial effect of vitamin C in respect to human disease such as cancer, atherosclerosis, diabetes, neurodegenerative disease and metal toxicity however remains equivocal. Thus further continuous uninterrupted efforts may open new vistas to understand its significance in disease management.

9.
Adv Exp Med Biol ; 617: 387-94, 2008.
Article in English | MEDLINE | ID: mdl-18497062

ABSTRACT

Residues of organochlorine pesticides are integral part of our environment. Because of their strong lipophilic and non-biodegradable nature, organisms at higher trophic levels in the food chain tend to accumulate them. The aim of the present study was to assess the influence of organochlorine pesticides upon the occurrence of reproductive tract cancers in women from Jaipur, India. Blood samples were collected from 150 females. In that group, 100 females suffered from reproductive tract cancers like cervical, uterine, vaginal and ovarian cancers, while the rest did not suffer from cancers or any other major disease and were treated as control group. The collected blood samples were subjected to pesticide extraction and analyzed with the help of gas chromatography. The pesticides detected were benzene hexa chlororide and its isomers, dieldrin, heptachlor, dichloro diphenyl trichloro ethane and its metabolites. The data obtained indicate that the organochlorine pesticide residue levels were significantly higher in all the cancer patients as compared with the control group.


Subject(s)
Hydrocarbons, Chlorinated/blood , Ovarian Neoplasms/epidemiology , Pesticide Residues/blood , Uterine Cervical Neoplasms/epidemiology , Vaginal Neoplasms/epidemiology , Adult , Chromatography, Gas , Female , Humans , Incidence , India , Middle Aged , Ovarian Neoplasms/blood , Risk Factors , Uterine Cervical Neoplasms/blood , Vaginal Neoplasms/blood
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