Brahma Rasayana enhances in vivo antioxidant status in cold-stressed chickens (Gallus gallus domesticus)

Objective:

To evaluate the antioxidant status of chicken during cold stress and to investigate if there are any beneficial effects of Brahma Rasayana supplementation in cold stressed chicken.

Materials and Methods:

Activities of enzymatic and levels of non-enzymatic antioxidants in blood / serum and liver tissue were evaluated in chicken exposed to cold (4 ± 10C and relative humidity of 40 ± 5%, for six consecutive hours daily, for 5 or 10 days). The antioxidant properties of Brahma Rasayana (BR) supplementation (2 g/kg daily, orally) during cold stress was also studied.

Results:

There was a significant (P < 0.05) decrease in antioxidant enzyme in the blood, such as, superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), and serum reduced glutathione (GSH) in cold stressed chicken. Serum and liver lipid peroxidation levels were significantly (P < 0.05) higher in cold stressed untreated chickens when compared to the treated and unstressed groups. There was also a significant (P < 0.05) increase in the antioxidant enzymes in the blood, such as, catalase (CAT) and SOD, in the liver CAT and SOD, and in GPX and GR in BR-treated cold stressed chicken, when compared to the untreated controls.

Conclusions:

Results of the present study conclude that in chicken, BR supplementation during cold stress brings about enhanced actions of the enzymatic and non-enzymatic antioxidants, which nullify the undesired side effects of free radicals generated during cold stress.     

Single-dose oral toxicity study of a cross-linked sodium polyacrylate/polyvinyl alcohol copolymer in chickens (Gallus domesticus)

A single-dose oral toxicity study of a grafted copolymer of cross-linked sodium polyacrylate with polyvinyl alcohol was conducted in chickens (Gallus domesticus) to demonstrate this copolymer's safety for use as a hydration medium in recently hatched poultry chicks. Three experimental groups, each composed of 25 male and 25 female 1-day-old chicks, were administered a one-time dose of 0, 3, or 6 g of the hydrated test article by gavage. All chicks were monitored daily for mortality and morbidity during their typical grow-out period of approximately 8 weeks. Interim sacrifices of one animal of each sex from each treatment group were made at 1, 2, 4, and 6 weeks. All surviving animals were necropsied at the end of the study. A single dose of up to 6 g of hydrated copolymer did not adversely affect these animals during their grow-out period. Mortality was comparable across all experimental groups, as no statistically significant survival differences were found. Body weights were also comparable across the three experimental groups at all time points during the study, and no statistically significant differences were detected in mean terminal body weights among the groups. Finally, lesion frequencies were similar across the three experimental groups, with none of the lesions deemed related to administration of the test article. Thus, the safety of this cross-linked sodium polyacrylate/polyvinyl alcohol copolymer has been demonstrated for its intended use.     

Prenatal exposure to the pesticide metam sodium induces sensorimotor and neurobehavioral abnormalities in mice offspring

The present study has investigated developmental neurotoxicity of Metam sodium (MS), from gestational day 6 and throughout the gestation period until delivery. Therefore, mated female mice were orally exposed on a daily basis to 0 (control), 50, 100 or 150 mg of MS/kg of body weight and their standard fertility and reproductive parameters were assessed. The offspring were examined for their sensorimotor development, depression and cognitive performance. Our results showed that MS exposure during pregnancy led to one case of mortality, two cases of abortion and disturbed fertility and reproductive parameters in pregnant dams. In offspring, MS induced an overall delay in innate reflexes and sensorimotor performances. Furthermore, all prenatally treated animals showed an increased level of depression-like behavior as well as a pronounced cognitive impairment in adulthood. These results demonstrated that prenatal exposure to MS causes a long-lasting developmental neurotoxicity and alters a wide range of behavioral functions in mice.     

Nervous system effects of dissolved and nanoparticulate cadmium in rats in subacute exposure

Cadmium, a toxic heavy metal with various applications in technology, can affect people both by environmental (foodborne) and occupational (inhalation) exposure and can cause nervous system damage. To model this, rats were subacutely treated either with CdCl(2) solution per os (3.0 mg kg(-1) b.w.) or nanoparticulate CdO(2) (particle size ca 65 nm) by intratracheal instillation (0.04 mg kg(-1) b.w.) alone or in sequential combination. Nervous system effects were observed at different levels of function (open field behavior, cortical electrical activity, nerve action potential) and some general toxicological indicators were also measured. Three weeks of oral plus one week of intratracheal exposure caused significant reduction of body weight gain and open field motility. Lengthening of latency of sensory evoked potentials, observed in all treated rats, was also the most significant in the group receiving oral plus intratracheal treatment. Conduction velocity of the tail nerve was likewise decreased in all treated groups. Several of the effects pointed to a potentiating interaction between the two forms of Cd. Modeling environmental and occupational Cd exposure by oral and intratracheal application in rats was feasible, with results suggesting serious negative health effects in humans suffering such a combined exposure.     

Haemotoxicity to chicken (Gallus gallus domesticus) by technical and formulation grades of some phosphoric and synthetic pyrethroid esters

Acute toxicity was studied by administering an encapsulated single dose to chickens (G.g. domesticus) and observing them for 21 days. Azodrin-71 (Tech.) was found to be extremely toxic, whereas Cypermethrin-92 (Tech.), Cypermethrin-25 EC and Permasect-25 EC (Form.) were practically non-toxic based on LD50 value determinations. Sub-acute oral haemotoxicity of technical and formulation grades of these insecticides was also studied by administering encapsulated low, medium and high daily doses for 21 days to chickens and recording clinical symptoms, mortality and haematological parameters pre and post-dosing. Clinically high doses of Azodrin-71 (Tech.) caused tremors and ataxia among chicks on the 10th day after dosing. Synthetic pyrethroids caused slight tremours in the whole body accompanied by salivation. In general, hyperactivity to external stimuli and loss of appetite and body weight were also observed. With sub-acute oral doses, Permasect-25 EC (Form.) more potently affected haemoglobin (Hb), red cell (RBC) counts and chloride level. Cypermethrin-92 (Tech.) was most potent towards thrombocytes and clotting time. Azodrin-71 (Tech.) was more potent to white cell (WBC) counts and serum protein level. The present Haematological studies have disclosed the possible reaction of blood and blood forming organs to these insecticides.     

Developmental immunotoxicity in male rats after juvenile exposure to di-n-octyltin dichloride (DOTC)

To determine relevant endpoints for evaluating developmental immunotoxicity due to juvenile exposure and optimal age of the animals at assessment, a wide range of immunological parameters were assessed in a juvenile toxicity study. Rats were exposed to di-n-octyltin dichloride (DOTC) by gavage from postnatal day (PND) 10 through PND 21 and via the diet after weaning using a benchmark dose (BMD) approach. Immune assessments were performed in male rats on PNDs 21, 42, and 70 and a subset of animals was used to evaluate the T-cell dependent antibody response (TDAR) to Keyhole limpet hemocyanin. Immune effects were more pronounced on PND 21 and 42 and observed at lower doses than developmental effects. The most sensitive immune parameters affected included TDAR parameters and thymocyte subpopulations with lower confidence limits of the benchmark doses (BMDLs) below the overall no-observed-adverse-effect-level (NOAEL) for DOTC reported so far in literature. These findings illustrate the relative sensitivity of the developing immune system for DOTC, the additional value of assessing functional immune parameters, and underscore the relevance of juvenile immunotoxicity testing in view of the risk assessment of chemicals.     

Influence of some dopaminoceptor agents on nitrazepam-induced sleep in the domestic fowl (Gallus domesticus) and rats

The influence of apomorphine, levodopa and haloperidol was studied on nitrazepam sleep using young chicks and rats. In addition, the influence of dopamine and ADTN was studied in young chicks. Nitrazepam dose-dependently (0.4-51.2 mg/kg, i.p.) induced behavioural sleep in chicks. However, higher doses of nitrazepam (12.8-51.2 mg/kg, i.p.) were required to induce behavioural sleep in rats. Dopamine (12.5-100 mg/kg, i.p.) and ADTN (2.5-80 mg/kg, i.p.) delayed the onset but prolonged nitrazepam sleep in chicks: these effects were statistically significant. Levodopa (12.5-100 mg/kg, s.c.) and apomorphine (0.2-0.8 mg/kg, s.c.) profoundly delayed the onset and shortened the duration of nitrazepam sleep in both chicks and rats. Noradrenaline (20-80 mg/kg, i.p.) shortened the onset and prolonged nitrazepam sleep in chicks. Pimozide (1-8 mg/kg, i.p.) potentiated nitrazepam sleep and antagonized the effects of dopamine, levodopa and ADTN on nitrazepam sleep in chicks. Similarly, haloperidol (0.5-1.0 mg/kg, i.p.) potentiated nitrazepam sleep and antagonized the effects of levodopa and apomorphine on nitrazepam sleep in rats. The EEG synchronization and decreased EMG induced by nitrazepam (1.6 mg/kg, i.p., and 12.8 mg/kg, i.p., for chicks and rats, respectively) were antagonized by levodopa (12.5 mg/kg, s.c.). The behavioural and electroencephalographical results suggest that enhancement of dopaminergic neurotransmission may be involved in the mechanisms of wakefulness in both chicks and rats.     

Influence of dopamine, levodopa and apomorphine on maximal electroconvulsive seizure in the domestic fowl (Gallus domesticus)

The influence of dopamine, levodopa and apomorphine on maximal electroconvulsive seizure was studied in young chicks, adult cocks and rats. The susceptibility of chicks to maximal electroshock seizure increased with age between 1 to 7 days. Low to moderate doses of dopamine (12.5-150 mg/kg, i.p.), levodopa (6.25-25 mg/kg, s.c.) and apomorphine (0.25-2.0 mg/kg, s.c.) significantly (P less than 0.005) protected chicks against electroshock seizure, while high doses (200-400 mg/kg, i.p. of dopamine, 50-200 mg/kg, s.c. of levodopa and 2.5-5 mg/kg, s.c. of apomorphine) enhanced electroshock seizure in 1 to 7 day old chicks. However, when 14 day old chicks were used, these dopaminoceptor agonists protected the chicks against maximal electroshock seizure. Noradrenaline (1-40 mg/kg, i.p.) had no significant effect on electroshock seizure in chicks. Both pimozide (4 mg/kg, i.p.) and haloperidol (0.4 mg/kg, i.p.) antagonized the effects of levodopa (12.5 and 50.0 mg/kg, i.p.) and apomorphine (0.5-5 mg/kg, s.c.) on maximal electroshock seizure. The seizure susceptibility of both adult rats and fowls to electroshock was not altered by dopamine (12.5-400 mg/kg, i.p.). Central dopamine neurotransmission might be involved in the biphasic dose-dependent effects of dopamine, levodopa and apomorphine on maximal electroshock seizure in young chicks.     

Update: Mode of action (MOA) for liver tumors induced by oral exposure to 1,4-dioxane

Previous work has shown that the weight of evidence supports the hypothesis that 1,4-dioxane causes liver tumors in rodents through cytotoxicity and subsequent regenerative hyperplasia. Questions regarding a lack of concordant findings for this mode of action (MOA) in mice have not been resolved, however. In the current work, a reanalysis of data from two chronic mouse cancer bioassays on 1,4-dioxane, one 13-week mouse study, seven rat cancer bioassays, coupled with other data such as 1,4-dioxane's negative mutagenicity, its lack of up-regulated DNA repair, and the appearance of liver tumors with a high background incidence, support the conclusion that rodent liver tumors, including those in mice, are evoked by a regenerative hyperplasia MOA. The initiating event for this MOA is metabolic saturation of 1,4-dioxane. Above metabolic saturation, higher doses of the parent compound cause an ever increasing toxicity in the rodent liver as evidenced by higher blood levels of enzymes indicative of liver cell damage and associated histopathology that occurs in a dose and time related manner. Importantly, alternative modes of action can be excluded. The observed liver toxicity has a threshold in the dose scale at or below levels that saturate metabolism, and generally in the range of 9.6–42 mg/kg-day for rats and 57 to 66 mg/kg-day for mice. It follows that threshold approaches to the assessment of this chemical's toxicity are supported by the non-mutagenic, metabolic saturation kinetics, and cytotoxicity-generated regenerative repair information available for 1,4-dioxane promoted rodent liver tumors.     

Biomarkers of exposure,effect, and susceptibility in occupational exposure to traffic-related air pollution: A review

There is a well-recognized association between environmental air pollution exposure and several human diseases. However, the relationship between diseases related to occupational air pollution exposure on roads and high levels of traffic-related air pollutants (TRAPs) is less substantiated. Biomarkers are essential tools in environmental and occupational toxicology, and studies on new biomarkers are increasingly relevant due to the need to determine early biomarkers to be assessed in exposure conditions. This review aimed to investigate the main advances in the biomonitoring of subjects occupationally exposed to air pollution, as well as to summarize the biomarkers of exposure, effect, and susceptibility. Furthermore, we discuss how biomarkers could be used to complement the current application of methods used to assess occupational exposures to xenobiotics present in air pollution. The databases used in the preparation of this review were PubMed, Scopus, and Science Direct. Considering the significant deleterious effects on health associated with chronic occupational exposure to xenobiotics, this topic deserves attention. As it is difficult to avoid occupational exposure to TRAPs, biomonitoring should be applied as a strategy to reduce the toxic effects of workplace exposure.     

Effects of in utero and lactational exposure to SbV on rat neurobehavioral development and fertility

Meglumine antimoniate (MA) is a pentavalent antimony drug used to treat leishmaniases. We investigated the neurobehavioral development, sexual maturation and fertility of the offspring of MA-treated rats. Dams were administered MA (0, 75, 150, 300 mg Sb^V/kg body wt/d, sc) from gestation day 0, throughout parturition and lactation, until weaning. At the highest dose, MA reduced the birth weight and the number of viable newborns. In the male offspring, MA did not impair development (somatic, reflex maturation, weight gain, puberty onset, open field test), sperm count, or reproductive performance. Except for a minor effect on body weight gain and vertical exploration in the open field, MA also did not affect the development of female offspring. Measurements of the Sb levels (ICP-MS) in the blood of MA-treated female rats and their offspring demonstrated that Sb is transferred to the fetuses via the placenta and to the suckling pups via milk.     

Evaluation of neurobehavioral and neuroinflammatory end-points in the post-exposure period in rats sub-acutely exposed to manganese

Manganese (Mn) can cause manganism, a neurological disorder similar to Parkinson’ Disease (PD). The neurobehavioral and neuroinflammatory end-points in the Mn post exposure period have not been studied yet. Rats were injected on alternate days with 8 doses of MnCl₂ (25 mg/kg) or saline, then euthanized 1, 10, 30 or 70 days following the last dose. Whole-blood (WB) (p < 0.05), urine (p < 0.05) and brain cortical (p < 0.0001) Mn levels were significantly increased 24 h after the last dose. Decreases in the rats’ ambulation were noted 1, 10 and 30 days after the last Mn dose (p < 0.001; p < 0.05; p < 0.001, respectively) and also in the rearing activity at the four time-points (p < 0.05). Cortical glial fibrillary acid protein immunoreactivity (GFAP-ir) was significantly increased at 1, 10, 30 (p < 0.0001) and 70 (p < 0.001) days after the last Mn dose, as well as tumor necrosis α (TNF-α) levels (p < 0.05) but just on day 1. Taken together, the results show that, during the 70-day clearance phase of Mn, the recovery is not immediate as behavioral alterations and neuroinflammation persist long after Mn is cleared from the cortical brain compartment.     

Failure of ethanol or pentobarbital to suppress fighting in the pit gamecock (Gallus gallus)

The pit gamecock (Gallus gallus) provides a model of strong trained aggression. A total of 16 aggressive pairs was treated with pentobarbital (40 or 60 mg/kg, intramuscularly), or ethanol (10–30 ml/kg of 33% v/v ethanol, by gastric intubation), or ethanol plus immobilization. Pairs of treated cocks were allowed to recover together in one cage. Fighting behavior occurred immediately upon recovery of the second cock of each pair. Thus, recovery from anesthesia in pairs failed to attenuate aggressive behavior in the gamecock, contrary to the marked attenuation previously observed in the male rabbit.     

Dioxin-Like and Non-Dioxin-Like Toxic Effects of Polychlorinated Biphenyls (PCBs): Implications For Risk Assessment

Polychlorinated biphenyls (PCBs) are persistent, bioaccumulative, and toxic contaminants in the environment. Individual PCB congeners exhibit different phy sicochemical properties and biological activities that result in different environmental distributions and toxicity profiles. The variable composition of PCB residues in environmental matrices and their different mechanisms of toxicity complicate the development of scientifically based regulations for the risk assessment. In this article various approaches for the assessment of risks of PCBs have been critically examined. Recent developments in the toxic equivalency factor (TEF) approach for the assessment of toxic effects due to dioxin-like PCBs have been examined. PCB exposure studies that describe non-dioxin-like toxic effects, particularly neurobehavioral effects and their effective doses in animals were compiled. A comparative assessment of effective doses for dioxin-like and non-dioxin-like effects by PCBs has been made to evaluate the relative significance of non-ortho-and ortho-substituted PCBs in risk assessment. Using mink as an example, relative merits and implications of using TEF and total PCB approaches for assessing the potential for toxic effects in wildlife was examined. There are several advantages and limitations associated with each method used for PCB risk assessment. Toxic effects due to coplanar PCBs occur at relatively smaller concentrations than those due to non-dioxin-like PCBs and therefore the TEF approach derives the risk assessment of PCBs, in the environment. The need for the refinement of TEF approach for more accurate assessment of risks is discussed.     

Adverse effects of fipronil on avian reproduction and development: maternal transfer of fipronil to eggs in zebra finch Taeniopygia guttata and in ovo exposure in chickens Gallus domesticus

Two studies were carried out to examine the impact of maternal fipronil exposure on embryonic and offspring development. In the first study, breeding female zebra finches were orally dosed with single sublethal levels of fipronil (1, 5, and 10 mg/kg body weight) to determine behavioural and developmental consequences on chicks following maternal pesticide exposure. Significant levels of fipronil and fipronil-sulfone residues were detected in eggs laid by females in all dosed groups, however, these were undetectable in eggs laid 13 days after treatment. The level of sulfone detected in eggs was consistently higher than that of the parent fipronil compound. Of the seven eggs laid in the treatment groups, only one (14%) chick hatched and this was from the lowest dose group. This chick was severely underdeveloped at 10 days of age in comparison to control chicks and fiproles were detected in brain, liver, and adipose tissues collected following euthanasia of this individual. In contrast, there was 100% hatchability of control group eggs and all chicks fledged nests on schedule. In the second study, domestic chicken eggs were injected with 5.5, 17.5, and 37.5 mg/kg egg weight of fipronil directly into the yolk sac on day 12 of incubation. Treatment did not affect hatching success, however, behavioural and developmental abnormalities were observed in hatchlings from the highest dose group. These chicks also demonstrated reduced feeding rates, as indicated by reduced body mass at 48 h period post hatch. Both fipronil and fipronil-sulfone residues were detected in brain and liver tissue of hatchlings at all pesticide dose levels tested.     

The comparative toxicity of a reduced,crude comfrey (Symphytum officinale) alkaloid extract and the pure,comfrey‐derived pyrrolizidine alkaloids,lycopsamine and intermedine in chicks (Gallus gallus domesticus)

Comfrey (Symphytum officinale), a commonly used herb, contains dehydropyrrolizidine alkaloids that, as a group of bioactive metabolites, are potentially hepatotoxic, pneumotoxic, genotoxic and carcinogenic. Consequently, regulatory agencies and international health organizations have recommended comfrey be used for external use only. However, in many locations comfrey continues to be ingested as a tisane or as a leafy vegetable. The objective of this work was to compare the toxicity of a crude, reduced comfrey alkaloid extract to purified lycopsamine and intermedine that are major constituents of S. officinale. Male, California White chicks were orally exposed to daily doses of 0.04, 0.13, 0.26, 0.52 and 1.04 mmol lycopsamine, intermedine or reduced comfrey extract per kg bodyweight (BW) for 10 days. After another 7 days chicks were euthanized. Based on clinical signs of poisoning, serum biochemistry, and histopathological analysis the reduced comfrey extract was more toxic than lycopsamine and intermedine. This work suggests a greater than additive effect of the individual alkaloids and/or a more potent toxicity of the acetylated derivatives in the reduced comfrey extract. It also suggests that safety recommendations based on purified compounds may underestimate the potential toxicity of comfrey. Published 2015. This article has been contributed to by US Government employees and their work is in the public domain in the USA.