Effects of combined exposure to dichlorvos and monocrotophos on blood and brain biochemical variables in rats

2009 ◽  
Vol 29 (2) ◽  
pp. 121-129 ◽  
Author(s):  
Nidhi Dwivedi ◽  
Yangchen D Bhutia ◽  
Vinesh Kumar ◽  
Preeti Yadav ◽  
Pramod Kushwaha ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Synergistic Effects ◽  
Brain Regions ◽  
Serum Glucose ◽  
Female Rats ◽  
Biochemical Variables ◽  
Aspartate Amino Transferase ◽  
Brain Ache Activity ◽  
Concomitant Exposure ◽  
Cholinergic Effects

Dichlorvos (DDVP) and monocrotophos (MC) are systemic insecticides and known to produce cholinergic and non-cholinergic effects. Individual toxic effects of these chemicals are known but their combined effects have not been studied. We studied the effect of concomitant exposure to DDVP and MC on selected biochemical variables suggestive of liver damage, changes in whole brain biogenic amines levels, acetylcholinesterase (AchE) and monoamine oxidase (MAO) activities in rats. Female rats were exposed to DDVP (2.5 mg/kg subcutaneously) and MC (1.8 mg/kg oral) either individually or in combination for 4 weeks. We observed significant decrease in more pronounced depletion in norepinephrine (NE) and dopamine (DA) levels during co-exposure to DDVP and MC. Brain AChE activity increased and activity of MAO showed significant depletion on co-exposure to DDVP and MC. Brain glutathione (GSH) and oxidized glutathione (GSSG) ratio decreased significantly during exposure to DDVP or MC while co-exposure to these toxicants led to a more pronounced depletion of GSH: GSSG ratio. Serum aspartate amino transferase (AST) and alkaline phosphatase (ALP) activities increased significantly on exposure to MC suggesting liver injury, while DDVP alone had no effect on these variables. There were no effects of DDVP and MC exposure on haematological biochemical variables except for depletion in serum glucose level after MC exposure which was more pronounced DDVP + MC during co-exposure. It can be concluded that only moderate synergistic effects occur between MC and DDVP during co-exposure. A more detailed study with variable doses, prolonged exposure and alterations in different brain regions is recommended.

Interleukin-1 Receptor Type I mRNA Levels in Brain Regions From Male and Female Rats

1997 ◽  
Vol 42 (6) ◽  
pp. 463-467 ◽  
Author(s):  
Dave Gayle ◽  
Sergey E. Ilyin ◽  
Carlos R. Plata-Salamán
Keyword(s):  
Interleukin 1 ◽  
Brain Regions ◽  
Female Rats ◽  
Receptor Type ◽  
Type I ◽  
Mrna Levels ◽  
Male And Female ◽  
Male And Female Rats

Maternal sucrose consumption alters behaviour and steroids in adult rat offspring

2021 ◽  
Author(s):  
Daniel J Tobiansky ◽  
George V Kachkovski ◽  
Reilly T Enos ◽  
Kim L Schmidt ◽  
E. Angela Murphy ◽  
...  
Keyword(s):  
Steroid Receptors ◽  
Control Diet ◽  
Female Offspring ◽  
Brain Regions ◽  
Female Rats ◽  
Mrna Levels ◽  
Sucrose Intake ◽  
Sucrose Consumption ◽  
Adult Rat ◽  
Specific Effects

Maternal diets can have dramatic effects on the physiology, metabolism, and behaviour of offspring that persist into adulthood. However, the effects of maternal sucrose consumption on offspring remain unclear. Here, female rats were fed either a sucrose diet with a human-relevant level of sucrose (25% of kcal) or a macronutrient-matched, isocaloric control diet before, during, and after pregnancy. After weaning, all offspring were fed a standard low-sucrose rodent chow. We measured indicators of metabolism (weight, adipose, glucose tolerance, liver lipids) during development and adulthood (16-24 wk). We also measured food preference and motivation for sugar rewards in adulthood. Finally, in brain regions regulating these behaviours, we measured steroids and transcripts for steroidogenic enzymes, steroid receptors, and dopamine receptors. In male offspring, maternal sucrose intake decreased body mass and visceral adipose, increased preference for high-sucrose and high-fat diets, increased motivation for sugar rewards, and decreased mRNA levels of Cyp17a1 (an androgenic enzyme) in the nucleus accumbens. In female offspring, maternal sucrose intake increased basal corticosterone levels. These data demonstrate the profound, enduring, diverse, and sex-specific effects of maternal sucrose consumption on offspring phenotype.

scholarly journals Prenatal EDCs Impair Mate and Odor Preference and Activation of the VMN in Male and Female Rats

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Morgan E Hernandez Scudder ◽  
Amy Weinberg ◽  
Lindsay Thompson ◽  
David Crews ◽  
Andrea C Gore
Keyword(s):  
Preference Test ◽  
Brain Regions ◽  
Female Rats ◽  
Early Gene ◽  
Odor Preference ◽  
Pregnant Rat ◽  
Discrimination Ability ◽  
Preference Behavior ◽  
Male And Female Rats ◽  
Aroclor 1221

Abstract Environmental endocrine-disrupting chemicals (EDCs) disrupt hormone-dependent biological processes. We examined how prenatal exposure to EDCs act in a sex-specific manner to disrupt social and olfactory behaviors in adulthood and underlying neurobiological mechanisms. Pregnant rat dams were injected daily from embryonic day 8 to 18 with 1 mg/kg Aroclor 1221 (A1221), 1 mg/kg vinclozolin, or the vehicle (6% DMSO in sesame oil). A1221 is a mixture of polychlorinated biphenyls (weakly estrogenic) while vinclozolin is a fungicide (anti-androgenic). Adult male offspring exposed to A1221 or vinclozolin, and females exposed to A1221, had impaired mate preference behavior when given a choice between 2 opposite-sex rats that differed by hormone status. A similar pattern of impairment was observed in an odor preference test for urine-soaked filter paper from the same rat groups. A habituation/dishabituation test revealed that all rats had normal odor discrimination ability. Because of the importance of the ventrolateral portion of the ventromedial nucleus (VMNvl) in mate choice, expression of the immediate early gene product Fos was measured, along with its co-expression in estrogen receptor alpha (ERα) cells. A1221 females with impaired mate and odor preference behavior also had increased neuronal activation in the VMNvl, although not specific to ERα-expressing neurons. Interestingly, males exposed to EDCs had normal Fos expression in this region, suggesting that other neurons and/or brain regions mediate these effects. The high conservation of hormonal, olfactory, and behavioral traits necessary for reproductive success means that EDC contamination and its ability to alter these traits has widespread effects on wildlife and humans.

Indicators of oxidative stress in weanling and pubertal rats following exposure to nicotine via milk

2009 ◽  
Vol 29 (6) ◽  
pp. 489-496 ◽  
Author(s):  
Ben Ahmed Halima ◽  
Khlifi Sarra ◽  
Rtibi Kais ◽  
Elfazaa Salwa ◽  
Gharbi Najoua
Keyword(s):  
Oxidative Stress ◽  
Wistar Rats ◽  
Female Rats ◽  
Male Rats ◽  
Nicotine Exposure ◽  
Lactation Period ◽  
Aspartate Amino Transferase ◽  
Males And Females ◽  
Breast Fed ◽  
Biomarkers Of Oxidative Stress

Nicotine, a major toxic component of tobacco, has been identified as an important risk factor for infant and children diseases. It is concentrated in breast milk and is absorbed by the infant. The purpose of the present study was to investigate the effects of maternal nicotine exposure during lactation on breast-fed rats and at the pubertal age by measuring biomarkers of oxidative stress. Particularly, a new parameter, the thiol concentration was evaluated. Two groups of lactating Wistar rats were used. For the first group, female rats were given an intraperitoenal injection of nicotine or saline (2 mg/kg per day) during lactation. For the second group, we reproduced the same process described above and then the female and male pups were separately kept after weaning without any treatment until the puberty (at 45 days of age). In the liver and lung of the offspring, we examined the malondialdehyde (MDA) level, the thiol concentration, and the activities of two antioxidant enzymes: superoxyde dismutase (SOD) and catalase (CAT). In the plasma, alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were measured. For rats aged 21 days, the treatment significantly reduced the thiol concentration, SOD, and CAT activities but increased MDA level, AST, and ALT activities. For rats aged 45 days, the males and females did not react the same way. In fact, the males were more affected. These results indicate that maternal nicotine exposure during the lactation period induces oxidative stress in the liver and lung of lactating offspring, which is maintained until the puberty, especially for the male rats.

Nonclinical Safety of the Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin

2014 ◽  
Vol 33 (6) ◽  
pp. 436-449 ◽  
Author(s):  
Matthew S. Bogdanffy ◽  
Robert F. Stachlewitz ◽  
Susan van Tongeren ◽  
Brian Knight ◽  
Dale E. Sharp ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Tubular Epithelial Cell ◽  
Serum Glucose ◽  
Global Market ◽  
Female Rats ◽  
Male Rats ◽  
Clinical Dose ◽  
Sodium Glucose Cotransporter ◽  
Nervous System Function ◽  
Renal Tubular

Empagliflozin, a selective inhibitor of the renal tubular sodium-glucose cotransporter 2, was developed for treatment of type 2 diabetes mellitus. Nonclinical safety of empagliflozin was studied in a battery of tests to support global market authorization. Safety pharmacology studies indicated no effect of empagliflozin on measures of respiratory or central nervous system function in rats or cardiovascular safety in telemeterized dogs. In CD-1 mouse, Wistar Han rat, or beagle dogs up to 13, 26, or 52 weeks of treatment, respectively, empagliflozin exhibited a toxicity profile consistent with secondary supratherapeutic pharmacology related to glucose loss and included decreased body weight and body fat, increased food consumption, diarrhea, dehydration, decreased serum glucose and increases in other serum parameters reflective of increased protein catabolism, gluconeogenesis, and electrolyte imbalances, and urinary changes such as polyuria and glucosuria. Microscopic changes were consistently observed in kidney and included tubular nephropathy and interstitial nephritis (dog), renal mineralization (rat) and tubular epithelial cell karyomegaly, single cell necrosis, cystic hyperplasia, and hypertrophy (mouse). Empagliflozin was not genotoxic. Empagliflozin was not carcinogenic in female mice or female rats. Renal adenoma and carcinoma were induced in male mice only at exposures 45 times the maximum clinical dose. These tumors were associated with a spectrum of nonneoplastic changes suggestive of a nongenotoxic, cytotoxic, and cellular proliferation-driven mechanism. In male rats, testicular interstitial cell tumors and hemangiomas of the mesenteric lymph node were observed; both tumors are common in rats and are unlikely to be relevant to humans. These studies demonstrate the nonclinical safety of empagliflozin.

Effect of nintedanib, a triple angiokinase inhibitor, on EGFR and HER2 in colorectal cancer (CRC) models, and rational for its combinations with the ErbB family blocker afatinib.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 485-485
Author(s):  
Annette K. Larsen ◽  
Aimery de Gramont ◽  
Aude Batistella ◽  
Arnaud Afchain ◽  
Paul Mésange ◽  
...  
Keyword(s):  
Side Effects ◽  
Prolonged Exposure ◽  
Synergistic Effects ◽  
Angiogenesis Inhibitor ◽  
Synergistic Activity ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Erbb Family ◽  
Combination Methods ◽  
Erbb Family Blocker

485 Background: We have recently shown that combinations of afatinib, a pan-HER/ErbB blocker, and nintedanib, a triple angiokinase (VEGFR, FGFR, PDGFR) inhibitor show synergistic activity in CRC models (Poindessous et al., Clin Cancer Res. 17:6522, 2011). However, the mechanistic basis for the synergistic effects of the combination is incompletely understood. EGFR is activated following exposure to a wide variety of therapeutic modalities including ionizing irradiation and irinotecan. We speculated that nintedanib exposure could also activate EGFR signaling which might explain the synergistic activity of the combination. Methods: Mice with human CRC xenografts were treated with nintedanib and afatinib alone or in combination and the influence on tumor growth, viability and the presence of phosphorylated HER family members was determined. Different scheduling regimens were explored to identify an administration schedule which combined optimal antitumor activity with minimal toxic side effects. Results: We here show that nintedanib treatment results in activation of EGFR and HER2 in multiple CRC xenograft models in a dose-dependent manner. Among the different regimens tested, continuous nintedanib with administration of afatinib every second week proved almost as efficient as continuous administration of the two agents together and was less toxic. Finally, nintedanib plus afatinib was superior to nintedanib alone in three different tumor xenografts with mutant KRAS. Conclusions: We here report that prolonged exposure to nintedanib, a small molecule angiogenesis inhibitor, is accompanied by activation of EGFR and HER2. Accordingly, afatinib, an ErbB family blocker, was synergistic with nintedanib. We subsequently identified a novel regimen for optimizing the antitumor effects of the combination with limited toxic side effects and showed that this regimen is active in four different CRC tumor models including three with mutant KRAS. These findings provide a rationale for clinical trials of the two small molecules, even in patients with mutant KRAS.

scholarly journals Local Cerebral Glucose Utilization in Normal Female Rats: Variations during the Estrous Cycle and Comparison with Males

1985 ◽  
Vol 5 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Astrid Nehlig ◽  
Linda J. Porrino ◽  
Alison M. Crane ◽  
Louis Sokoloff
Keyword(s):  
Estrous Cycle ◽  
Glucose Utilization ◽  
Brain Regions ◽  
Female Rats ◽  
Male Rats ◽  
Normal Male ◽  
Normal Female ◽  
Female Rat ◽  
Males And Females ◽  
The Brain

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.

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