scholarly journals Chlorpyrifos- and Dichlorvos-Induced Oxidative and Neurogenic Damage Elicits Neuro-Cognitive Deficits and Increases Anxiety-Like Behavior in Wild-Type Rats

Toxics ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 71 ◽  
Author(s):  
Aminu Imam ◽  
Nafeesah Abdulkareem Sulaiman ◽  
Aboyeji Lukuman Oyewole ◽  
Samson Chengetanai ◽  
Victoria Williams ◽  
...  

The execution of agricultural activities on an industrial scale has led to indiscriminate deposition of toxic xenobiotics, including organophosphates, in the biome. This has led to intoxication characterized by deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to a combination of two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP), on neuro-cognitive performance and anxiety-like behaviors in rats. Thirty-two adult male Wistar rats (150–170 g) were randomly divided into four groups, orally exposed to normal saline (NS), DDVP (8.8 mg/kg), CPF (14.9 mg/kg), and DDVP + CPF for 14 consecutive days. On day 10 of exposure, anxiety-like behavior and amygdala-dependent fear learning were assessed using open field and elevated plus maze paradigms, respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following three training trials on days 11, 12, and 13. On day 15, the rats were euthanized, and their brains excised, with the hippocampus and amygdala removed. Five of these samples were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three were processed for histology (cresyl violet stain) and proliferative markers (Ki67 immunohistochemistry). Marked (p ≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p ≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damage are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.

Author(s):  
Aminu Imam ◽  
Nafeesah Abdulkareem Sulaiman ◽  
Aboyeji Lukuman Oyewole ◽  
Samson Chengetanai ◽  
Victoria Williams ◽  
...  

The mechanization of agricultural activities has led to indiscriminate deposition of toxic xenobiotics, including organophosphates in the biomes, and this has led to intoxication characterized with deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP) on neuro-cognitive performance and anxiety-like behaviors in rats Thirty-two adult male Wistar rats (150 – 170g) were randomly divided into 4 groups, orally exposed to normal saline (NS), DDVP (8.8mg/kg), CPF (14.9mg/kg) and DDVP+CPF for 14 consecutive days. On day 10 of exposures, anxiety-like behaviors and amygdala dependent fear learning were assessed using Open Field and Elevated Plus Maze paradigms respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following 3 training trials each on days 11, 12 and 13. On day 15, the rats were euthanized, and their brains excised, hippocampus and amygdala removed, 5 of which were homogenized and centrifuged to analyze nitric  oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three processed for histology (cresyl violet stain) and proliferative marker (Ki67 immunohistochemistry). Marked (p≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damages are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.


2020 ◽  
Vol 14 (1) ◽  
pp. 99-107
Author(s):  
Huba Kalász ◽  
Gellért Karvaly ◽  
Ferenc Szimrók ◽  
Dóra Szabó ◽  
Márton Milánkovits ◽  
...  

Background: Our recent work has been treating the pharmacokinetics of pyridinium aldoximes of various structures including their time-dependent distribution in the body of male rats and also the extent of blood-brain-barrier penetration. Objective: Our overall aim was to find a proper antidote in organophosphate poisoning with fast elimination. Methods: White male Wistar rats were intramuscularly injected with the aqueous solution of 3 µmol of K-347. The animals were sacrificed at different time periods following treatment; various tissues and body fluids were taken and homogenised. The level of K-347 was determined using reversed-phase HPLC. Dose-dependence of tissue level was also determined by using various doses, 3 µmol through 100 µmol of K-347. Results: The serum level of K-347 showed a definitely fast decline. K347 did not have any effect on Gram-positive and Gram-negative bacteria that we tested. Conclusion: The kinetics of K-347 showed an extremely fast offset, even in comparison with several other pyridinium aldoximes in clinical practice and in developmental stages.


2014 ◽  
Vol 84 (1-2) ◽  
pp. 5-11 ◽  
Author(s):  
Eun Y. Jung ◽  
Sung C. Jun ◽  
Un J. Chang ◽  
Hyung J. Suh

Previously, we have found that the addition of L-ascorbic acid to chitosan enhanced the reduction in body weight gain in guinea pigs fed a high-fat diet. We hypothesized that the addition of L-ascorbic acid to chitosan would accelerate the reduction of body weight in humans, similar to the animal model. Overweight subjects administered chitosan with or without L-ascorbic acid for 8 weeks, were assigned to three groups: Control group (N = 26, placebo, vehicle only), Chito group (N = 27, 3 g/day chitosan), and Chito-vita group (N = 27, 3 g/day chitosan plus 2 g/day L-ascorbic acid). The body weights and body mass index (BMI) of the Chito and Chito-vita groups decreased significantly (p < 0.05) compared to the Control group. The BMI of the Chito-vita group decreased significantly compared to the Chito group (Chito: -1.0 kg/m2 vs. Chito-vita: -1.6 kg/m2, p < 0.05). The results showed that the chitosan enhanced reduction of body weight and BMI was accentuated by the addition of L-ascorbic acid. The fat mass, percentage body fat, body circumference, and skinfold thickness in the Chito and Chito-vita groups decreased more than the Control group; however, these parameters were not significantly different between the three groups. Chitosan combined with L-ascorbic acid may be useful for controlling body weight.


2020 ◽  
Vol 20 (8) ◽  
pp. 1262-1267
Author(s):  
Haojun Yang ◽  
Hanyang Liu ◽  
YuWen Jiao ◽  
Jun Qian

Background: G protein-coupled bile acid receptor (TGR5) is involved in a number of metabolic diseases. The aim of this study was to identify the role of TGR5 after Roux-en-Y gastric bypass (GBP). Methods: Wild type and TGR5 knockout mice (tgr5-/-) were fed a high-fat diet (HFD) to establish the obesity model. GBP was performed. The changes in body weight and food intake were measured. The levels of TGR5 and peptide YY (PYY) were evaluated by RT-PCR, Western blot, and ELISA. Moreover, the L-cells were separated from wild type and tgr5-/- mice. The levels of PYY in L-cells were evaluated by ELISA. Results: The body weights were significantly decreased after GBP in wild type mice (p<0.05), but not tgr5-/- mice (p>0.05). Food intake was reduced after GBP in wild type mice, but also not significantly affected in tgr5-/- mice (p>0.05). The levels of PYY were significantly increased after GBP compared with the sham group (p<0.05); however, in tgr5-/- mice the expression of PYY was not significantly affected (p>0.05). After INT-777 stimulation in L-cells obtained from murine intestines, the levels of PYY were significantly increased in L-cells tgr5+/+ (p<0.05). Conclusion: Our study suggests that GBP up-regulated the expression of TGR5 in murine intestines, and increased the levels of PYY, which further reduced food intake and decreased the body weight.


2021 ◽  
Vol 11 (4) ◽  
pp. 423
Author(s):  
Markus Fendt ◽  
Claudia Paulina Gonzalez-Guerrero ◽  
Evelyn Kahl

Rats can acquire fear by observing conspecifics that express fear in the presence of conditioned fear stimuli. This process is called observational fear learning and is based on the social transmission of the demonstrator rat’s emotion and the induction of an empathy-like or anxiety state in the observer. The aim of the present study was to investigate the role of trait anxiety and ultrasonic vocalization in observational fear learning. Two experiments with male Wistar rats were performed. In the first experiment, trait anxiety was assessed in a light–dark box test before the rats were submitted to the observational fear learning procedure. In the second experiment, ultrasonic vocalization was recorded throughout the whole observational fear learning procedure, and 22 kHz and 50 kHz calls were analyzed. The results of our study show that trait anxiety differently affects direct fear learning and observational fear learning. Direct fear learning was more pronounced with higher trait anxiety, while observational fear learning was the best with a medium-level of trait anxiety. There were no indications in the present study that ultrasonic vocalization, especially emission of 22 kHz calls, but also 50 kHz calls, are critical for observational fear learning.


Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 469
Author(s):  
Ying Zhang ◽  
Hengyu Zhang ◽  
Yunfeng Zhao ◽  
Xiaojing Zhou ◽  
Jie Du ◽  
...  

In animal breeding, body components and metabolic traits always fall behind body weights in genetic improvement, which leads to the decline in standards and qualities of animal products. Phenotypically, the relative growth of multiple body components and metabolic traits relative to body weights are characterized by using joint allometric scaling models, and then random regression models (RRMs) are constructed to map quantitative trait loci (QTLs) for relative grwoth allometries of body compositions and metabolic traits in chicken. Referred to as real joint allometric scaling models, statistical utility of the so-called LASSO-RRM mapping method is given a demonstration by computer simulation analysis. Using the F2 population by crossing broiler × Fayoumi, we formulated optimal joint allometric scaling models of fat, shank weight (shank-w) and liver as well as thyroxine (T4) and glucose (GLC) to body weights. For body compositions, a total of 9 QTLs, including 4 additive and 5 dominant QTLs, were detected to control the allometric scalings of fat, shank-w, and liver to body weights; while a total of 10 QTLs of which 6 were dominant, were mapped to govern the allometries of T4 and GLC to body weights. We characterized relative growths of body compositions and metabolic traits to body weights in broilers with joint allometric scaling models and detected QTLs for the allometry scalings of the relative growths by using RRMs. The identified QTLs, including their highly linked genetic markers, could be used to order relative growths of the body components or metabolic traits to body weights in marker-assisted breeding programs for improving the standard and quality of broiler meat products.


1985 ◽  
Vol 249 (2) ◽  
pp. R159-R165 ◽  
Author(s):  
G. L. Florant ◽  
A. K. Lawrence ◽  
K. Williams ◽  
W. A. Bauman

Fasting plasma insulin (PI) and glucose (PG) concentrations were measured throughout the body weight cycle of marmots. Animals gained weight during summer, and in late fall body weight peaked, after which they ceased feeding. Each month euthermic animals were injected intra-arterially with either dextrose (500 mg/kg) or porcine insulin (0.1 U/kg), and blood samples were collected over the subsequent 2 h. During weight gain fasting PI concentration and pancreatic B-cell response to injected dextrose increased markedly. Maximal insulin release to a dextrose challenge was measured during peak body weight or when body weight initially began to decline. The PG concentration after exogenous insulin administration was slight (less than 10%) in the fall but increased approximately 25% in the spring after marmots lost weight. Basal PG levels were not significantly different throughout the year. Basal fasting PI concentrations were significantly higher during the fall (P less than 0.01). It is suggested that in the fall, when marmots are obese, hyperinsulinemia and peripheral insulin resistance appear. Furthermore, in two animals with an increase in body weight of approximately 30% or less over the summer, peripheral resistance was demonstrable, albeit not as marked as in animals that appropriately doubled their body weights when given food ad libitum. Thus we hypothesize that factors other than adiposity, i.e., food intake, central nervous system input to the pancreatic B-cell, and/or changes in B-cell sensitivity to PG, may contribute to the observed peripheral insulin resistance and may be involved in body weight regulation.


1969 ◽  
Vol 62 (2) ◽  
pp. 367-384 ◽  
Author(s):  
A. M. Sackler ◽  
A. S. Weltman ◽  
R. Schwartz ◽  
P. Steinglass

ABSTRACT This report was designed to determine combined effects of maternal endocrine imbalances and abnormal behaviour due to prolonged isolation stress of female mice on the behaviour, developmental growth rate and endocrine function of their offspring. Sixty female albino mice averaging 19 g were divided equally into isolated and control groups. The isolated females were housed singly; control females were maintained in groups of 2 mice per cage. After observation of behavioural and physiological effects characteristic of isolation stress in the test mice, all isolated and control mice were mated after a 6½ month experimental, isolation period. No differences were observed in fertility and fecundity of the two groups of mothers. Analyses of developmental growth rates of the litters of the isolated versus control mothers showed significantly lower body weights in the test offspring at 3 and 4 weeks of age. The body weights of the female offspring remained significantly lower from the 4th to 11th weeks. The effects on the body weights of the male offspring declined and were no longer statistically significant at the 5th to 11 weeks. Locomotor activity at 4½ and 8 weeks of age was markedly or significantly higher in the male and female mice from isolated mothers. Tail-blood samples taken prior to autopsy at 5 and 11 weeks of age revealed significant decreases in the total leukocyte and eosinophil counts of both sexes. At the two ages, the absolute and relative spleen and thymus weights of the male and female offspring were markedly and/or significantly lower than the values observed in counterpart young from control females. Significant decreases were also observed in the absolute gonadal organ weights of both sexes at 11 weeks of age. The various data indicated inhibited growth rates, heightened locomotor activity and evasiveness, as well as evidence of increased adrenocortical function in the offspring from test mothers. The gonadal weight decreases suggested retarded gonadal development. Further studies using split-litter techniques are required to differentiate the effects of prenatal endocrine imbalances versus postnatal maternal influence (i. e., nursing care) on the offspring.


1989 ◽  
Vol 98 (5) ◽  
pp. 359-363 ◽  
Author(s):  
Patricia A. Schachern ◽  
Michael M. Paparella ◽  
Donald A. Shea ◽  
Tae H. Yoon

Fabry's disease is a rare progressive X-linked recessive disorder of glycosphingolipid metabolism. The accumulation of glycosphingolipids occurs in virtually all areas of the body, including the endothelial, perithelial, and smooth-muscle cells of blood vessels, the ganglion cells of the autonomic nervous system, and the glomeruli and tubules of the kidney. Although otologic symptoms have been described in these patients, to our knowledge there have been no temporal bone histopathologic reports. We describe the clinical histories, audiometric results, and temporal bone findings of two patients with this rare disorder. Both patients demonstrated a bilateral sloping sensorineural hearing loss audiometrically. Middle ear findings of seropurulent effusions and hyperplastic mucosa were seen in all four temporal bones. Strial and spiral ligament atrophy in all turns, and hair cell loss mainly in the basal turns, were also common findings. The number of spiral ganglion cells was reduced in all temporal bones; however, evidence of glycosphingolipid accumulation was not observed in the spiral ganglia.


2015 ◽  
Vol 105 (4) ◽  
pp. 390-398 ◽  
Author(s):  
P.-J. Wan ◽  
L. Yang ◽  
S.-Y. Yuan ◽  
Y.-H. Tang ◽  
Q. Fu ◽  
...  

AbstractThe brown planthopper Nilaparvata lugens is a serious phloem-feeding pest of rice in China. The current study focuses on a saccharopine dehydrogenase (SDH) that catalyzes the penultimate reaction in biosynthesis of the amino acid lysine (Lys), which plays a role in insect growth and carnitine production (as a substrate). The protein, provisionally designated as NlylsSDH [a SDH derived from yeast-like symbiont (YLS) in N. lugens], had a higher transcript level in abdomens, compared with heads, wings, legs and thoraces, which agrees with YLS distribution in N. lugens. Ingestion of Nlylssdh targeted double-stranded RNA (dsNlylssdh) for 5, 10 and 15 days decreased the mRNA abundance in the hoppers by 47, 70 and 31%, respectively, comparing with those ingesting normal or dsegfp diets. Nlylssdh knockdown slightly decreased the body weights, significantly delayed the development of females, and killed approximately 30% of the nymphs. Moreover, some surviving adults showed two apparent phenotypic defects: wing deformation and nymphal cuticles remained on tips of the legs and abdomens. The brachypterours/macropterours and sex ratios (female/male) of the adults on the dsRNA diet were lowered compared with the adults on diets without dsRNA. These results suggest that Nlylssdh encodes a functional SDH protein. The adverse effect of Nlylssdh knockdown on N. lugens implies the importance of Lys in hopper development. This study provides a proof of concept example that Nlylssdh could serve as a possible dsRNA-based pesticide for planthopper control.


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