Electrothermal transport of third-order fluids regulated by peristaltic pumping.

The study of heat and electroosmotic characteristics in the flow of a third-order fluid regulated by peristaltic pumping is examined by using governing equations, i.e., the continuity equation, momentum equation, energy equation, and concentration equation. The wavelength is considered long compared to its height and a low Reynolds number is assumed. The velocity slip condition is employed. Analytical solutions are performed through the perturbation technique. The expressions for the dimensionless velocity components, temperature, concentration, and heat transfer rate are obtained. Pumping features were computed numerically for discussion of results. Trapping and heat transfer coefficient distributions were also studied graphically. The findings of the present study can be applied to design biomicrofluidic devices like tumor-on-a-chip and organ-on-a-chip.

Numerical simulation of heat transfer in blood flow altered by electroosmosis through tapered micro-vessels.

A numerical simulation is presented to study the heat and flow characteristics of blood flow altered by electroosmosis through the tapered micro-vessels. Blood is assumed as non-Newtonian (micropolar) nanofluids. The flow regime is considered as asymmetric diverging (tapered) microchannel for more realistic micro-vessels which is produced by choosing the peristaltic wave train on the walls to have different amplitudes and phase. The Rosseland approximation is employed to model the radiation heat transfer and temperatures of the walls are presumed constants. The mathematical formulation of the present problem is simplified under the long-wavelength, low-Reynolds number and Debye-Hückel linearization approximations. The influence of various dominant physical parameters are discussed for axial velocity, microrotation distribution, thermal temperature distribution and nanoparticle volume fraction field. However, our foremost emphasis is to determine the effects of thermal radiation and coupling number on the axial velocity and microrotation distribution beneath electroosmotic environment. This analysis places a significant observation on the thermal radiation and coupling number which plays an influential role in hearten fluid velocity. This study is encouraged by exploring the nanofluid-dynamics in peristaltic transport as symbolized by heat transport in biological flows and also in novel pharmacodynamics pumps and gastro-intestinal motility enhancement.

Joule heating and zeta potential effects on peristaltic blood flow through porous micro vessels altered by electrohydrodynamic.

In most of the medical therapies, electromagnetic field plays important role to modulate the blood flow and to reduce the pain of human body. With this fact, this paper presents a mathematical model to study the peristaltic blood flow through porous microvessels in the presence of electrohydrodynamics. The effects of Joule heating and different zeta potential are also considered. Darcy law is employed for porous medium. The mathematical analysis is carried out in the form of electroosmosis, flow analysis and heat transfer analysis. Velocity slip conditions are imposed to solve momentum equation and thermal energy equation. Time dependent volumetric flow rate is considered which varies exponentially. Closed form solutions for potential function is obtained under Debye-Hückel approximation and velocity and temperature fields are obtained under low Reynolds number and large wavelength approximations. The influence of Hartmann number, electroosmotic parameter, slip parameters, Zeta potential, and couple stress parameter on flow characteristics, pumping characteristics and trapping phenomenon is computed. The effects of thermal slip parameters, Joule heating parameter, and Brinkman number on heat transfer characteristics are also presented graphically. Finally, the effect of Brinkman number on a graph between Nusselt number and Joule heating parameter is examined.

Progression of blood-borne viruses through bloodstream: A comparative mathematical study.

BACKGROUND AND OBJECTIVES: Blood-borne pathogens are contagious microorganisms that can cause life-threatening illnesses, and are found in human blood. It is crucial to examine how these viruses spread through blood flow in the blood vessel. Keeping that in view, this study aims to determine how blood viscosity, and diameter of the viruses can affect the virus transmission through the blood flow in the blood vessel. A comparative study of bloodborne viruses (BBVs) such as HIV, Hepatitis B, and C, has been addressed in the present model. A couple stress fluid model is used to represent blood as a carrying medium for virus transmission. The Basset-Boussinesq-Oseen equation is taken into account for the simulation of virus transmission. METHODS: An analytical approach to derive the exact solutions under the assumption of long wavelength and low Reynolds number approximations is employed. For the computation of the results, a segment (wavelength) of blood vessels about 120 mm with wave velocities in the range of 49 - 190 mm/sec are considered, where the diameter of BBVs ranges from 40-120 nm. The viscosity of the blood varies from 3.5-5.5 × 10-3Ns/m2 which affect the virion motion having a density range 1.03 - 1. 25 g/m3. RESULTS: It shows that the Hepatitis B virus is more harmful than other blood-borne viruses considered in the analysis. Patients with high blood pressure are highly susceptible for transmission of BBVs. CONCLUSIONS: The present fluid dynamics approach for virus spread through blood flow can be helpful in understanding the dynamics of virus propagation inside the human circulatory system.

Computation of stagnation coating flow of electro-conductive ternary Williamson hybrid [Formula: see text] nanofluid with a Cattaneo-Christov heat flux model and magnetic induction.

Modern smart coating systems are increasingly exploiting functional materials which combine multiple features including rheology, electromagnetic properties and nanotechnological capabilities and provide a range of advantages in diverse operations including medical, energy and transport designs (aerospace, marine, automotive). The simulation of the industrial synthesis of these multi-faceted coatings (including stagnation flow deposition processes) requires advanced mathematical models which can address multiple effects simultaneously. Inspired by these requests, this study investigates the interconnected magnetohydrodynamic non-Newtonian movement and thermal transfer in the Hiemenz plane's stagnation flow. Additionally, it explores the application of a transverse static magnetic field to a ternary hybrid nanofluid coating through theoretical and numerical analysis. The base fluid (polymeric) considered is engine-oil (EO) doped with graphene [Formula: see text], gold [Formula: see text] and Cobalt oxide [Formula: see text] nanoparticles. The model includes the integration of non-linear radiation, heat source, convective wall heating, and magnetic induction effects. For non-Newtonian characteristics, the Williamson model is utilized, while the Rosseland diffusion flux model is used for radiative transfer. Additionally, a non-Fourier Cattaneo-Christov heat flux model is utilized to include thermal relaxation effects. The governing partial differential conservation equations for mass, momentum, energy and magnetic induction are rendered into a system of coupled self-similar and non-linear ordinary differential equations (ODEs) with boundary restrictions using appropriate scaling transformations. The dimensionless boundary value problem that arises is solved using the bvp4c built-in function in MATLAB software, which employs the fourth-order Runge-Kutta (RK-4) method. An extensive examination is conducted to evaluate the impact of essential control parameters on the velocity [Formula: see text], induced magnetic field stream function gradient [Formula: see text] and temperature [Formula: see text] is conducted. The relative performance of ternary, hybrid binary and unitary nanofluids for all transport characteristics is evaluated. The inclusion of verification of the MATLAB solutions with prior studies is incorporated. Fluid velocity is observed to be minimized for the ternary [Formula: see text]-[Formula: see text]-[Formula: see text] nanofluid whereas the velocity is maximized for the unitary cobalt oxide [Formula: see text] nanofluid with increasing magnetic parameter ([Formula: see text] Temperatures are elevated with increment in thermal radiation parameter (Rd). Streamlines are strongly modified in local regions with greater viscoelasticity i.e. higher Weissenberg number [Formula: see text]. Dimensionless skin friction is significantly greater for the ternary hybrid [Formula: see text]-[Formula: see text]-[Formula: see text] nanofluid compared with binary hybrid or unitary nanofluid cases.

Quercetin inhibits diethylnitrosamine-induced hepatic preneoplastic lesions in rats.

Quercetin is an antioxidant flavonoid, found ubiquitously in nature and extensively used in herbal medicines and food additives. This study aimed to investigate the effect of quercetin on diethylnitrosamine-induced preneoplastic lesions, using the medium-term rat liver bioassay. The γ-benzene hexachloride was used as promoter at the doses of 0.1, 1.0, and 10.0 mg/kg against a single dose of diethylnitrosamine (200 mg/kg) in male Sprague-Dawley rats. All the rats were subjected to 70% partial hepatectomy at Week 4. The protective effect of quercetin (5 and 25 mg/kg) was examined against the highest dose of γ-benzene hexachloride (10 mg/kg). A significant increase in the number as well as the mean area of glutathione S-transferase placental form (GST-P) positive foci, p53 positive hepatocytes, and the percentage of apoptotic cells were observed in the diethylnitrosamine-treated group. In the present investigation, both doses of QC (5 and 25 mg/kg) led to a significant decrease in the number as well as the mean area of GST-P positive foci, TUNEL positive apoptotic cells, p53 positive hepatocytes, and restoration of cellular morphology. These results clearly indicate that quercetin inhibits diethylnitrosamine-induced hepatic preneoplastic lesions in medium-term rat liver bioassay.

Nitric oxide (NO) and salicylic acid (SA): A framework for their relationship in plant development under abiotic stress.

The free radical nitric oxide (NO) and the phenolic phytohormone salicylic acid (SA) are signal molecules which exert key functions at biochemical and physiological levels. Abiotic stresses, especially in early plant development, impose the biggest threats to agricultural systems and crop yield. These stresses impair plant growth and subsequently cause a reduction in root development, affecting nutrient uptake and crop productivity. The molecules NO and SA have been identified as robust tools for efficiently mitigating the negative effects of abiotic stress in plants. SA is engaged in an array of tasks under adverse environmental situations. The function of NO depends on its cellular concentration; at a low level, it acts as a signal molecule, while at a high level, it triggers nitro-oxidative stress. The crosstalk between NO and SA involving different signalling molecules and regulatory factors modulate plant function during stressful situations. Crosstalk between these two signalling molecules induces plant tolerance to abiotic stress and needs further investigation. This review aims to highlight signalling aspects of NO and SA in higher plants and critically discusses the roles of these two molecules in alleviating abiotic stress.

Scoping review on the role and interactions of hydroxytyrosol and alpha-cyclodextrin in lipid-raft-mediated endocytosis of SARS-CoV-2 and bioinformatic molecular docking studies.

OBJECTIVE: The aim of the study was to show the effect that two naturally occurring compounds, a cyclodextrin and hydroxytyrosol, can have on the entry of SARS-CoV-2 into human cells. MATERIALS AND METHODS: The PubMed database was searched to retrieve studies published from 2000 to 2020, satisfying the inclusion criteria. The search keywords were: SARS-CoV, SARS-CoV-2, coronavirus, lipid raft, endocytosis, hydroxytyrosol, cyclodextrin. Modeling of alpha-cyclodextrin and hydroxytyrosol were done using UCSF Chimera 1.14. RESULTS: The search results indicated that cyclodextrins can reduce the efficiency of viral endocytosis and that hydroxytyrosol has antiviral properties. Bioinformatic docking studies showed that alpha-cyclodextrin and hydroxytyrosol, alone or in combination, interact with the viral spike protein and its host cell receptor ACE2, thereby potentially influencing the endocytosis process. CONCLUSIONS: Hydroxytyrosol and alpha-cyclodextrin can be useful against the spread of SARS-CoV-2.

Effect of melatonin on the expression of Nrf2 and NF-kappaB during cyclophosphamide-induced urinary bladder injury in rat.

Urotoxicity is one of the major problems associated with cyclophosphamide (CP) chemotherapy in cancer patients. Melatonin is a potent antioxidant and reduces CP-induced urotoxicity. However, the molecular mechanisms of protection offered by melatonin are not yet clear. The present study investigated the role of nuclear erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-kappaB) on melatonin-mediated protection against CP-induced urotoxicity. CP was administered intraperitoneally at the dose of 150 mg/kg to induce urotoxicity in male Sprague-Dawley rats. Melatonin treatment (10 mg/kg) was initiated 3 days before and continued for 1 day after the CP administration. Melatonin treatment reduced the CP-induced oxidative stress and DNA damage in the urinary bladder as observed by abrogation in thiobarbituric acid-reactive substances and glutathione levels as well as comet and modified comet assay parameters. Melatonin treatment reduced the bladder damage and apoptosis as observed by histological analysis and TUNEL assay. Melatonin increased the expression of transcription factor Nrf2 as well as associated phase-II enzymes NADPH: quinone oxidoreductase-1 and heme oxygenase-1. Further melatonin treatment reduced the expression of transcription factor NF-kappaB. The results of the present study provide evidence that melatonin treatment favorably alters Nrf2 and NF-kappaB expression and, this appears to be at least in part responsible for observed protection against CP-induced urotoxicity.

Astaxanthin intervention ameliorates cyclophosphamide-induced oxidative stress, DNA damage and early hepatocarcinogenesis in rat: role of Nrf2, p53, p38 and phase-II enzymes.

Cyclophosphamide, an alkylating agent, disturbs the oxidant and antioxidant balance that is associated with several unwanted toxic effects and induction of secondary cancers. Astaxanthin is a powerful antioxidant and possess several beneficial effects against various human diseases and physiological disorders. The present study was aimed to investigate the effects of astaxanthin against cyclophosphamide-induced oxidative stress, DNA damage, cell death and induction of GST-P foci in rat liver. Further attempt has been made to study the influence of astaxanthin on antioxidant response element (ARE) and the transcription factor Nrf2 (nuclear factor E(2)-related factor 2) in the induction of phase-II enzymes NAD(P)H: quinine oxidoreductase-1(NQO-1) and Hemoxygenase-1 (HO-1). Both pre- and post-treatment with astaxanthin (25mg/kg) decreased cyclophosphamide-induced oxidative stress and DNA damage in the liver as evident from the restoration in malondialdehyde and glutathione level as well as modified comet assay parameters. Significant decrease in the number as well as area of GST-P foci in rat hepatocytes was observed with astaxanthin post-treatment. Treatment with astaxanthin significantly decreased the expression of p53 and p38 as compared to cyclophosphamide treated group. It was further observed that the level of Nrf2 and phase-II enzymes, i.e. NQO-1 and HO-1 were increased with astaxanthin treatment. The present study confirms that astaxanthin is a potent antioxidant and attenuates oxidative stress, DNA damage, cell death as well as induction of early hepatocarcinogenesis in rat induced by cyclophosphamide. Our results provide the evidence that one of the mechanism of chemoprotection offered by astaxanthin is mediated through Nrf2-ARE pathway.

Evaluation of male germ cell toxicity in rats: correlation between sperm head morphology and sperm comet assay.

The present study was aimed to investigate the germ cell toxicity of doxorubicin and find out the possible correlation between sperm head morphological evaluation and sperm comet assay, which are used to assess male germ cell toxicity. The correlation between these two assays was validated using a potent germ cell toxicant, doxorubicin, in male Sprague-Dawley rats. Doxorubicin was administered intra-peritionally at the doses of 1.25, 2.5 and 5mg/kg weekly once for a period of 5 weeks and all the animals were sacrificed after 1 week of receiving the last dose. The germ cell toxicity of doxorubicin was assessed using oxidative stress parameters, sperm head morphology, sperm comet assay, halo assay and histology in testes as the end point of evaluation. A significant increase in the % abnormality in sperm head was found in the animals treated with 2.5 and 5mg/kg/week doxorubicin. Doxorubicin treatment significantly increased the DNA damage of sperm in a dose-dependent manner as observed by sperm comet assay parameters. A strong positive correlation was observed between the sperm head morphological evaluation and the sperm comet assay. Therefore, it can be concluded that the damage in genetic material of sperm may result into abnormalities in the sperm head morphology. The sperm head morphological evaluation is considered to be essential for the assessment of male germ cell toxicity by several regulatory bodies like the Organization for Economic Cooperation and Development (OECD) and the International Conference on Harmonization (ICH). However, acceptance of the sperm comet assay by regulatory authorities as a standard genotoxicity test for assessing male germ cell toxicity still requires further validation of the assay.

Evaluation of multi-organ DNA damage by comet assay from 28 days repeated dose oral toxicity test in mice: a practical approach for test integration in regulatory toxicity testing.

The use of comet assay is not new in the evaluation of genotoxic potential of different agents; however, its broad use in product safety for regulatory testing is a relatively new approach. The present study was aimed to integrate genotoxicity tests (micronucleus and comet assay) in 28 days repeated dose oral toxicity of methotrexate (MTX) in mice. MTX was administered at the dose of 0.5, 1 and 2mg/kg per oral repeatedly for 28 days in mice. The endpoints of evaluation for routine toxicity testing included body weight, organ weight, food intake, water intake, hematology and histology, while for the genotoxicity testing micronucleus and comet assay were used. There were no significant changes in food intake, water intake and organ weight; however, the body weight significantly decreased at the highest dose of MTX treatment as compared to control group. Histological data revealed the morphological alterations in the liver and lung cells at the highest dose of MTX treatment. Micronucleus assay results indicated that the highest dose of MTX led to significant increase in MNERTs/1000ERTs (P<0.001) as compared to control group. Further, percentage of reticulocytes (% RETs) was significantly decreased at the highest dose of MTX as compared to control group. Comet assay results indicate significant DNA damage in different organs induced by MTX as compared to control group. The results of the present study successfully demonstrates the integration of genotoxicity tests using comet and micronucleus assay in 28 days repeated dose oral toxicity test. Integration of genotoxicity test with routine toxicity test would reduce the cost of additional animals, test item and provide further information at an early stage of product development.

Antioxidant and antimutagenic effect of quercetin against DEN induced hepatotoxicity in rat.

Diethylnitrosamine (DEN), a potent hepatocarcinogen, is found in tobacco smoke, processed meat as well as in different food products. Quercetin (QC), a naturally occurring flavonoid has excellent antioxidant properties. The present study was aimed to investigate the chemoprotective potential of QC against DEN induced hepatotoxicity in Sprague-Dawley (SD) rats. Quercetin was administered (10, 30 and 100 mg/kg) for 5 consecutive days after DEN (200 mg/kg) treatment. The animals were killed 24 h after the last dose of QC/saline treatment. The DEN induced hepatotoxicity was evident by elevated malondialdehyde (MDA) and decreased glutathione (GSH) levels in the liver. A significant increase in the levels of plasma aspartate transaminase (AST) and plasma alanine transaminase (ALT) was observed in the DEN treated group. The DEN induced DNA damage was evaluated using a single cell gel electrophoresis (SCGE) assay. A significant increase in the number of TUNEL positive cells was observed in the DEN treated group. Quercetin restored AST, ALT and GSH levels at all the tested doses. Restoration of the MDA level and cellular morphology was observed at doses of 10 and 30 mg/kg of QC. Further, DEN induced DNA damage and apoptosis was ameliorated by QC. The results indicate that QC ameliorates the DEN induced hepatotoxicity in rats and can be a candidate for a good chemoprotectant.

Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of folic and folinic acid.

Methotrexate (MTX) is an anti-metabolite widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The basis for its therapeutic efficacy is the inhibition of dihydrofolate reductase (DHFR), a key enzyme in the folic acid (FA) metabolism. FA is a water-soluble vitamin which is involved in the synthesis of purines and pyrimidines, the essential precursors of DNA. Folinic acid (FNA) is the reduced form of FA that circumvents the inhibition of DHFR. Folate supplementation during MTX therapy for psoriasis and inflammatory arthritis reduces both toxicity and side effects without compromising the efficacy. Further, FNA supplementation reduces the common side effects of MTX in the treatment of juvenile idiopathic arthritis. FA and FNA are reported to have protective effects on MTX-induced genotoxicity in the somatic cells; however their protective effects on the germ cells have not been much explored. Previously, we evaluated the cytotoxic and genotoxic effects of MTX in the germ cells of mice. In the present study, we have intervened FA and FNA for the protection of germ cell toxicity induced by MTX in male swiss mice. The animals were pre-treated with FA at the doses of 50, 100 and 200 microg/kg for 4 consecutive days per week and on day five; MTX was administered at the dose of 20mg/kg once. FNA was administered at the doses of 2.5, 5 and 10 mg/kg, 6 h (h) after single administration of MTX at the dose of 20 mg/kg. The dosing regimen was continued up to 10 weeks. The germ cell toxicity was evaluated using testes weight (wt), sperm count, sperm head morphology, sperm comet assay, histology, TUNEL and halo assay in testis. The results clearly demonstrate that prior administration of FA and post-treatment with FNA reduces the germ cell toxicity induced by MTX as evident from the decreased sperm head abnormalities, seminiferous tubule damage, sperm DNA damage, TUNEL positive cells and increased sperm counts. In the present study, we report that FA and FNA ameliorate the germ cell toxicity of MTX in mice.

Poly(methylmethacrylate) grafted chitosan: An efficient adsorbent for anionic azo dyes.

Present study reports on peroxydisulfate/ascorbic acid initiated synthesis of Chitosan-graft-poly(methylmethacrylate) (Ch-g-PMMA) and its characterization by FTIR, XRD and (13)C NMR. The copolymer remained water insoluble even under highly acidic conditions and was evaluated to be an efficient adsorbent for the three anionic azo dyes (Procion Yellow MX, Remazol Brilliant Violet and Reactive Blue H5G) over a wide pH range of 4-10 being most at pH 7. The adsorbent was also found efficient in decolorizing the textile industry wastewater and was much more efficient than the parent chitosan. Equilibrium sorption experiments were carried out at different pH and initial dye concentration values. The experimental equilibrium data for each adsorbent-dye system were successfully fitted to the Langmuir and Freundlich sorption isotherms. Based on Langmuir model Q(max) for yellow, violet and blue dyes was 250, 357 and 178, respectively. Thermodynamic parameters of the adsorption processes such as DeltaG degrees , DeltaH degrees , and DeltaS degrees were calculated. The negative values of free energy reflected the spontaneous nature of adsorption. The adsorption kinetic data of all the three dyes could be well represented by pseudo-second-order model with the correlation coefficients (R(2)) being 0.9922, 0.9997 and 0.9862, for direct yellow, reactive violet and blue dye, respectively with rate constants 0.91 x 10(-4), 1.82 x 10(-4) and 1.05 x 10(-4) g mg(-1)min(-1), respectively. At pH 7, parent chitosan also showed pseudo-second-order kinetics. The temperature dependence of dye uptake and the pseudo-second-order kinetics of the adsorption indicated that chemisorption is the rate-limiting step that controls the process.

Bleeding ectopic varices in cirrhosis: the role of transjugular intrahepatic portosystemic stent shunts.

BACKGROUND: Bleeding from ectopic varices is uncommon but can be difficult to manage. AIM: To report our experience of the use of transjugular intrahepatic portosystemic stent shunts (TIPSS) in the management of uncontrolled bleeding from ectopic varices. METHODS: A retrospective study of patients who had TIPSS for bleeding ectopic varices. Patients were selected from a dedicated data base. RESULTS: Over 14 years, of 750 TIPSS insertions, 28 patients had TIPSS for bleeding ectopic varices (Child-Pugh score: 8.8 +/- 1.8). Varices were rectal (12), stomal (8), duodenal (4) and at other sites (4). Concomitant variceal embolization was performed in five. Portal pressure gradient fell from 18.2 +/- 6.4 to 7.2 +/- 3.5 mmHg. TIPSS achieved haemostasis in six of nine patients who presented with active bleeding. Five patients rebled from ectopic varices. This was related to shunt dysfunction in two and responded to shunt interventions. Three patients rebled despite a functional shunt. Of these, thrombin controlled bleeding in one. Eight patients developed hepatic encephalopathy post-TIPSS. CONCLUSIONS: Transjugular intrahepatic portosystemic stent shunt is a safe and effective treatment for bleeding ectopic varices. Rebleeding from ectopic varices related to shunt dysfunction responds to shunt intervention. A significant proportion of patients have rebleeding despite a patent shunt, when other adjunctive measures like thrombin injection may be tried.

Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells.

Cyclophosphamide (CP), an alkylating agent used in the treatment of several cancers as well as an immunosuppressant in rheumatoid arthritis. It is used against several cancers due to its broad spectrum efficacy, but at the same time possesses unwanted risks for occupational exposure as well as therapy related toxicities to patients. The present study was aimed to investigate the protective effect of astaxanthin (AST) a red carotenoid pigment on CP induced germ cell toxicity in male mice. CP was administered intraperitoneally (i.p.) at the dose of 50, 100 and 200mg/kg body weight to mice (20-25 g) once in a week for a period of five weeks. AST was given at the dose of 25mg/kg per oral (p.o.) for five consecutive days in a week for five weeks. The animals were sacrificed one week after the last injection of CP. The protective effect of AST against CP induced male germ cell toxicity was evaluated using body weight, testes and epididymis weight, sperm count, sperm head morphology, sperm comet assay, histology of testes and TUNEL assay. AST treatment significantly improved the testes weight, sperm count and sperm head morphology as compared to only CP treated animals. The result of comet assay showed that AST treatment significantly restored the sperm DNA damage induced by CP. Further, AST treatment showed protection against CP induced testicular toxicity as evident from testes histology and TUNEL assay. The present results indicate the chemoprotective potential of AST against CP induced germ cell toxicity in mice.

Use of the alkaline comet assay for the detection of transplacental genotoxins in newborn mice.

Several lines of evidence show that in utero exposure to different toxicants has greater consequences than their exposure during adult life. This may be due to involvement of critical developmental stages, physiological immaturity and the long later-life span over which disease may initiate, develop and progress. The in vivo alkaline comet (single-cell gel electrophoresis) assay has been favoured by the scientific community for the evaluation of genotoxins. The objective of this study was to demonstrate the suitability of alkaline comet assay in detecting transplacental genotoxins using newborn mice. Here, we report the successful use of the comet assay in detecting multi-organ genotoxicity of known transplacental genotoxins in newborn mice. Three well known transplacental genotoxic agents, cyclophosphamide (CP), mitomycin-C (MMC) and zidovudine (AZT) were tested in pregnant Swiss mice. These compounds were administered in the late gestational period (16-20th days of pregnancy) and the comet assay was performed with lymphocytes, bone marrow, liver and kidney cells of newborn mice. Significant DNA damage was observed in all the tissues with tested transplacental genotoxins. The results of the comet assay were confirmed by the micronucleus (MN) assay of the peripheral blood of newborn mice. The results of this study provide sufficient evidence that the comet assay can be applied successfully for the detection of transplacental genotoxins in newborn mice.

Cytotoxic and genotoxic effects of methotrexate in germ cells of male Swiss mice.

Methotrexate (MTX) is an anti-metabolite drug widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. Developed as an analogue of folic acid, it inhibits purine and pyrimidine synthesis that accounts for its therapeutic efficacy as well as for its toxicities. MTX has narrow therapeutic index and its toxicity has been reported in various organ systems including gastrointestinal, haematologic and central nervous system. The objective of the present study is to investigate the germ cell toxicity induced by MTX in male Swiss mice. MTX was administered intraperitoneally (ip) at the doses of 5, 10, 20 and 40 mg/kg to mice (20-25 g) weekly once (wk) for 5 and 10 weeks. The animals were sacrificed 1 week after receiving the last treatment of MTX. The germ cell toxicity was evaluated using testes weight (wt), sperm count, sperm head morphology, sperm comet assay, histology, TUNEL and halo assay in testis. MTX treatment significantly reduced the sperm count and increased the occurrence of sperm head abnormalities in a dose dependent manner. It induced the testicular toxicity as evident from the histology of testis. Sperm comet, TUNEL and halo assay in testis also revealed significant DNA damage after MTX treatment. On the basis of the present study, it can be concluded that MTX induced germ cell toxicity in mice.