Activity In Male Rats Research Articles

Dietary copper-fructose interactions alter gut microbial activity in male rats.

Dietary copper-fructose interactions contribute to the development of nonalcoholic fatty liver disease (NAFLD). Gut microbiota play critical roles in the pathogenesis of NAFLD. The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbiome. Male weanling Sprague-Dawley rats were fed diets with adequate copper (6 ppm CuA), marginal copper (1.5 ppm CuM) (low copper), or supplemented copper (20 ppm CuS) (high copper) for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was given ad libitum. Copper status, liver enzymes, gut barrier function, and gut microbiome were evaluated. Both low- and high-copper diets led to liver injury in high-fructose-fed rats, and this was associated with gut barrier dysfunction, as shown by the markedly decreased tight junction proteins and increased gut permeability. 16S rDNA sequencing analysis revealed distinct alterations of the gut microbiome associated with dietary low- and high-copper/high-fructose feeding. The common features of the alterations of the gut microbiome were the increased abundance of Firmicutes and the depletion of Akkermansia. However, they differed mainly within the phylum Firmicutes. Our data demonstrated that a complex interplay among host, microbes, and dietary copper-fructose interaction regulates gut microbial metabolic activity, which may contribute to the development of liver injury and hepatic steatosis. The distinct alterations of gut microbial activity, which were associated with the different dietary doses of copper and fructose, imply that separate mechanism(s) may be involved. NEW & NOTEWORTHY First, dietary low- and high-copper/high-fructose-induced liver injury are associated with distinct alterations of gut microbiome. Second, dietary copper level plays a critical role in maintaining the gut barrier integrity, likely by acting on the intestinal tight junction proteins and the protective commensal bacteria Akkermansia. Third, the alterations of gut microbiome induced by dietary low and high copper with or without fructose differ mainly within the phylum Firmicutes.

Effect of pre- and post-weaning high-fat dietary manipulation on intestinal microflora and alkaline phosphatase activity in male rats.

We investigated the impact of a high-fat (HF) diet during pre- and post-weaning periods on the intestinal microbiota and alkaline phosphatase (AP) activity in male rats. Nutrition from birth was influenced by feeding rat dams with either a standard or HF diet. After weaning male pups nursed by control dams continued on a standard diet (CC) or HF diet (C->HF), while offspring nursed by HF dams continued on HF diet (HF) or standard diet (HF->C). The numbers of Bacteroides/Prevotella (BAC) and Lactobacillus/Enterococcus (LAB) in the gut were determined by FISH technique. HF pups displayed enhanced adiposity and increased AP activity (19 %), as well as higher LAB (P<0.001) and lower numbers of BAC (P<0.001) in the jejunum and colon than controls. In HF->C rats, post-weaning lower fat intake resulted in decreased fat deposition accompanied by reduced AP activity (20 %) compared to HF rats. Composition of the intestinal microbiota in these rats was not influenced. In contrast, in comparison with controls, C->HF rats displayed higher LAB (P<0.001) and lower BAC (P<0.001) together with increased adiposity and AP activity (14 %). These results indicate that consumption of diet with different fat content could modulate gut microbial/functional conditions depending on the period when the nutritional manipulation occurs.

Abstract 1240: Evaluating clinically relevant pharmacological agents in a rat ambulation model to ameliorate PEGylated recombinant hyaluronidase PH20 (PEGPH20)-mediated musculoskeletal adverse events

Abstract Some cancers accumulate high levels of the glycosaminoglycan hyaluronan (HA) within the tumor microenvironment (TME), and this HA accumulation is associated with rapid tumor progression and poor clinical outcomes. As preclinical data have demonstrated that enzymatic degradation of HA, via intravenous (IV) administration of PEGylated recombinant human hyaluronidase PH20 (PEGPH20), increases therapeutic efficacy in HA-accumulating tumors, several clinical trials evaluating PEGPH20 in combination with anti-cancer therapies are ongoing. The most advanced clinical trial (Phase 3) is evaluating PEGPH20 plus Abraxane® (nab-paclitaxel)/gemcitabine (AG) in patients with stage IV untreated pancreatic ductal adenocarcinoma (PDA)(NCT02715804). The safety profile of PEGPH20/Abraxane/gemcitabine (PAG) was generally similar to AG alone in an interim analysis of the Phase 2 data, with the exception of a potential imbalance of thromboembolic events (TEs), and an increased incidence of musculoskeletal events (MSEs) in the PAG arm, with the predominant MSE being muscle spasms (55.4% PAG vs. 1.6% AG, all grades)(Bullock, ASCO 2016). In an effort to find pharmacological agent(s) that might decrease MSEs in PAG-treated patients, a rat locomotor activity assay was developed. In brief, locomotor activity of male Sprague Dawley rats was measured with an automated infrared photobeam monitoring apparatus (Hamilton/Kinder®, San Diego) during the 12h dark cycle when rats are normally active. Any PEGPH20-mediated decrease in rat locomotor activity was interpreted as MSE-like effects. In response to PEGPH20 (1 mg/kg) the locomotor activity of male rats was reduced by ~75% for the first 2 dark cycles post-treatment (48h), and then gradually returned to vehicle baseline levels by days 4-5. FDA approved drugs used clinically to alleviate pain were subsequently tested for their ability to ameliorate the effects of PEGPH20 on locomotor activity. Agents included anti-inflammatories, anti-spasmodics, neuropathic pain medications, neuroleptics, diuretics, anti-hypertensives, anti-fibromyalgics and opioids. The steroid dexamethasone, currently being used in the Phase 2 and Phase 3 PDA clinical trials to manage MSEs, was the positive control. As a class, nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac, ketoprofen, diclofenac, and piroxicam, increased rat ambulation by ~40% on the first night following PEGPH20 treatment compared to PEGPH20 alone. Mobility in rats treated with NSAIDs/PEGPH20 increased ~60% on the second night compared to PEGPH20 alone. No other drug classes increased rodent ambulation. These data suggest that NSAIDs may be useful in partially alleviating the MSEs experienced by patients receiving PEGPH20. Citation Format: Li Ma, Marc R. Azar, Michael Shepard, Ya Huang, Piet A. Vervaet, Daniel C. Maneval, Curtis B. Thompson, Rudy Paladini. Evaluating clinically relevant pharmacological agents in a rat ambulation model to ameliorate PEGylated recombinant hyaluronidase PH20 (PEGPH20)-mediated musculoskeletal adverse events [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1240. doi:10.1158/1538-7445.AM2017-1240

Effects of Hypericum scabrum extract on learning and memory and oxidant/antioxidant status in rats fed a long-term high-fat diet.

A high-fat diet (HFD) causes deficits in learning and memory by increasing oxidative stress. Antioxidants are known to improve learning and memory. Since Hypericum scabrum (H. scabrum) extract is rich in antioxidants, the aim of this study was to investigate the effects of the administration of H. scabrum extract on passive avoidance learning (PAL), novel object recognition (NOR), and locomotor activity in male rats on a HFD. Fifty-four male Wistar rats (weighing 220±10g) were divided into the following six groups: (1) Control (standard diet), (2) Ext100 (standard diet supplemented with 100mg/kg extract once/day), (3) Ext300 (standard diet supplemented with 300mg/kg extract once/day), (4) HFD (high-fat diet), (5) HFD+Ext100, and (6) HFD+Ext300. Rats in these groups were maintained on their respective diets for 3months. In the PAL test, the step-through latencies in the retention test (STLr) were significantly higher in the HFD+extract group than in the HFD group. The time spent in the dark compartment (TDC) was significantly lesser and the time spent in exploring the novel object was significantly greater in the HFD+extract group than in the HFD group. In the HFD-fed rats, the activity of catalase had significantly decreased, and level of malondialdehyde had significantly increased; H. scabrum extract administration significantly reversed these changes. In conclusion, these results suggested that the administration of H. scabrum extract and its strong antioxidant properties enhanced learning and memory and reversed the memory impairment induced by chronic HFD consumption.

Effect of electrolytic lesion of the dorsomedial striatum on sexual behaviour and locomotor activity in rats

IntroductionCortical motor areas are influenced not only by peripheral sensory afferents and prefrontal association areas, but also by the basal ganglia, specifically the striatum. The dorsomedial striatum (DMS) and dorsolateral striatum are involved in both spatial and stimulus-response learning; however, each of these areas may mediate different components of learning. The aim of the study is to determine the effect of electrolytic lesion to the DMS on the learning and performance of sexual behaviour and locomotor activity in male rats. MethodOnce the subjects had learned to perform motor tests of balance, maze navigation, ramp ascent, and sexual behaviour, they underwent electrolytic lesion to the DMS. Five days later, the tests were repeated on 2 occasions and researchers compared performance latencies for each test. ResultsAverage latency values for performance on the maze and balance tests were higher after the lesion. However, the average values for the ramp test and for sexual behaviour did not differ between groups. ConclusionsElectrolytic lesion of the DMS modifies the performance of locomotor activity (maze test and balance), but not of sexual behaviour.

Study of the effect of zinc oxide on enzymatic antioxidant activity in male rats

Study of the effect of zinc oxide on enzymatic antioxidant activity in male rats

Dietary High and Low Copper‐Fructose Interactions Induce Hepatic Steatosis Associated with Distinct Alterations of Gut Microbial Activity in Male Rats

ObjectiveDietary copper‐fructose interactions play critical roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbial activity and the development of steatosis.MethodsMale weanling Sprague‐Dawley rats were fed diets with adequate copper (6 ppm, CuA), marginal copper (1.5 ppm, CuM) (low‐copper) or copper supplementation (20 ppm, CuS) (high‐copper) for 4 weeks. Deionized water or deionized water containing 30% fructose (w/v) was given ad lib. Copper status, liver enzymes, histology, gut barrier function and gut microbial activity were evaluated.ResultsCopper levels were significantly lower in rats fed with a marginal copper diet than in those fed with an adequate copper diet. However, high‐copper diet did not lead to excessive copper accumulation in the liver, likely due to the downregulation of copper transporter‐1(Ctr‐1) mRNA. Both low‐ and high‐copper diets led to liver injury and fat accumulation in high fructose fed rats, and this accumulation was associated with gut barrier dysfunction. The increased abundance of the gut Gram‐negative bacteria, Enterobacteriaceae, did not parallel plasma endotoxin levels, with low copper‐fructose induced steatosis being characterized with endotoxemia, whereas high copper‐fructose induced steatosis was not, despite the fact that both of these regimens resulted in increased gut permeability. Fecal metabolomics study and 16S rRNA gene expression analysis revealed distinct gut microbial metabolic characteristics in response to dietary low‐ and high‐copper high‐fructose feeding.ConclusionOur data demonstrated that dietary copper‐fructose interaction regulates gut microbial metabolic activity, which might contribute to the development of hepatic steatosis. The distinct alterations of gut microbial activity which were associated with the different dietary doses of copper and fructose imply that separate mechanism(s) may be involved.Support or Funding InformationThis study was supported in part by NIH Grants U01AA021901, U01AA022489, R01AA023681, an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM113226 and by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number P50AA024337. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (C.J.M.); K23AA018399, R01ES021375 (M.C.); the Veterans Administration (C.J.M.); and the U of L Clinical and Translational Pilot Program (C.J.M.).

Fertility enhancing activity and toxicity profile of aqueous extract of Chasmanthera dependens roots in male rats.

This study evaluated the fertility-enhancing activity and safety of aqueous extract of Chasmanthera dependens root (AECDR) in male rats. In the fertility study, twenty, sodium arsenite (10mg/kg) body weight (BW)-treated male rats (171.02±3.36g), assigned into four groups (I-IV), received 1ml of distilled water (DW), 25, 50 and 100mg/kg BW of AECDR for 60days, whereas the control received DW. After 7days of pairing with female rats (153.67±2.24g), spermatogenic, fertility, testicular function indices and enzymatic antioxidant activities were evaluated. The animal groupings in the toxicity study were similar to the fertility study except no administration of sodium arsenite. Sodium arsenite treatment-related decreases (p<.05) in the semen and sperm parameters, testicular function indices, antioxidant activities and female rat fertility indices were reversed/ameliorated by AECDR. AECDR significantly altered the function indices of the liver and kidney and the lipid profile and selectively altered the haematological parameters. There was no treatment-related histoarchitectural changes in the organs. Overall, the aqueous extract of C.dependens roots exhibited pro-spermatogenic, fertility enhancing, antioxidant and androgenic activities in male rats. It also exhibited functional toxicity. Therefore, the chronic use of AECDR may not be completely safe as oral remedy.

Taurine Supplementation Reduces Renal Nerve Activity in Male Rats in which Renal Nerve Activity was Increased by a High Sugar Diet.

This study tests the hypothesis that taurine supplementation reduces sugar-induced increases in renal sympathetic nerve activity related to renin release in adult male rats. After weaning, male rats were fed normal rat chow and drank water containing 5% glucose (CG) or water alone (CW) throughout the experiment. At 6-7 weeks of age, each group was supplemented with or without 3% taurine in drinking water until the end of experiment. At 7-8 weeks of age, blood chemistry and renal nerve activity were measured in anesthetized rats. Body weights slightly and significantly increased in CG compared to CW groups but were not significantly affected by taurine supplementation. Plasma electrolytes except bicarbonate, plasma creatinine, and blood urea nitrogen were not significantly different among the four groups. Mean arterial pressure significantly increased in both taurine treated groups compared to CW, while heart rates were not significantly different among the four groups. Further, all groups displayed similar renal nerve firing frequencies at rest and renal nerve responses to sodium nitroprusside and phenylephrine infusion. However, compared to CW group, CG significantly increased the power density of renin release-related frequency component, decreased that of sodium excretion-related frequency component, and decreased that of renal blood flow-related frequency component. Taurine supplementation completely abolished the effect of high sugar intake on renal sympathetic activity patterns. These data indicate that in adult male rats, high sugar intake alters the pattern but not firing frequency of sympathetic nerve activity to control renal function, and this effect can be improved by taurine supplementation.

The Relationship between Epiphyseal and Gonadal Activities in Male Rats in Different Seasons

The Relationship between Epiphyseal and Gonadal Activities in Male Rats in Different Seasons

Type of sweet flavour carrier affects thyroid axis activity in male rats

PurposeNon-nutritive sweeteners are the most widely used food additives worldwide. However, their metabolic outcomes are still a matter of controversy and their effect on the thyroid activity, a key regulator of metabolism, has not been previously studied. Therefore, we aim to determine the influence of the sweet type flavour carrier on selected parameters of thyroid axis activity.MethodsMale Sprague–Dawley rats (n = 105) were divided into 3 groups fed ad libitum for three weeks isocaloric diets (3.76 ± 0.5 kcal/g): two with the same sweet flavour intensity responded to 10% of sucrose (with sucrose–SC—and sucralose—SU) and one non-sweet diet (NS). To evaluate the post-ingested effects, animals were euthanised at fast and 30, 60, 120, 180 min after meal.ResultsThe results obtained indicate that both the presence and the type of sweet taste flavour carrier affect thyroid axis activity both at fasting and postprandial state. Compared to diet with sucrose which stimulates thyroid axis activity, sucralose addition diminishes thyroid hormone synthesis as thyroid peroxidase (TPO) activity, plasma thyroxine (T4), and triiodothyronine (T3) concentration was lower than in SC and NS while in non-sweet diet the lowest level of hepatic deiodinase type 1 (DIO1) and the highest reverse T3 (rT3) level indicate on altered thyroid hormone peripheral metabolism.ConclusionBoth the presence and the type of sweet flavour carrier have a significant impact on thyroid axis activity. Our findings suggest that this organochlorine sweetener is metabolically active and might exacerbate metabolic disorders via an adverse effect on thyroid hormone metabolism.

Sildenafil citrate-Glycyrrhizin/Eudragit binary spray dried microparticles: A sexual behavior studies on male rats

Sildenafil citrate (VIAGRA®) is a phosphodiasterase inhibitor 5 used for the treatment of male erectile dysfunction. Low aqueous solubility of sildenafil citrate limits their bioavailability and hence therapeutic effects. The aim of the present study was to develop a sildenafil citrate-Glycyrrhizin/Eudragit binary spray dried microparticles with a view to improve its aqueous solubility and examine its effect of sexual behavior on male rats. Microparticles of sildenafil citrate were prepared in three different ratios of sildenafil citrate-Glycyrrhizin/Eudragit (1:0.5, 1:1 & 1:2) by spray drying technique and evaluated for Particle size, size distribution, entrapment efficiency, DSC, FTIR, XRD, SEM and in vitro release studies. Among the six different formulae (F1, F2, F3, F4, F5, and F6), Glycyrrhizin (F2) and Eudragit (F4) based microparticles were optimized with an average particle size of 2.56 μm, 2.94 μm and high entrapment values 73.06%, 67.52% respectively. DSC, FTIR, and XRD confirmed the amorphous state of the encapsulated Sildenafil citrate. In vitro release studies exhibited significant results. Furthermore, its sexual behavior activity in male rats was much better as compared to pure sildenafil citrate. The overall results suggest that Glycyrrhizin based microparticles could be a potential option for sildenafil citrate delivery.

Anti-fertility effect of hydro-alcoholic extract of fennel (Foeniculum vulgare Mill) seed in male Wistar rats

Abstract Introduction: The study aimed to investigate the anti-fertility effect of fennel (Foeniculim vulgare Mill) seed extract in male rats. Material and Methods: Forty Wistar rats were divided into five equal groups. The control group received distilled water and the experimental groups were orally administered 1 ml of hydro-alcoholic extract of fennel seed in four doses of 35, 70, 140, and 280 mg/kg/b.w. daily for 60 days. After the last gavage, the rats were anaesthetised and the caudal part of the right epididymis was used for sperm counting. After fixation of the testes, microscopic sections were prepared and histological changes were evaluated. Results: The number of spermatogonia after doses of 140 and 280 mg/kg and Sertoli cells after a dose of 140 mg/kg decreased significantly as compared with the control group (P &lt; 0.05). The number of primary spermatocytes and sperm count decreased significantly in the experimental groups (70, 140, and 280 mg/kg) when compared to the control group (P &lt; 0.05). Furthermore, thickening of the basement membrane, cell apoptosis, and irregular arrangement of the germinal epithelium were observed in the experimental groups. Conclusion: Hydro-alcoholic fennel seed extract at these doses could reduce reproductivity and has anti-fertility activity in male rats.

Evaluating the protective effects of vitamin C on serum and erythrocyte cholinesterase activity of male rats exposed to malathion.

IntroductionMalathion is one of organophosphate poisons (OPPs) that inhibit cholinesterase activity and induce oxidative stress in target organs, such as the reproductive system. The aim of this study was to assess the effects of Malathion on serum and erythrocyte cholinesterase activity in male rats and also to assess the protective effects of vitamin C in this regard.MethodsThis experimental study was performed in the Pharmacology Laboratory of the Pharmacy Faculty and in the Advanced Histology Techniques Laboratory of the Medical Faculty of Mashhad University of Medical Sciences (MUMS) in January 2014. Thirty male wistar rats, weighting 200–250 g, were divided into five groups of six. The different groups were exposed as follows: group 1: Malathion 50 mg/kg; group 2: Vitamin C; group 3: Malathion plus Vitamin C with the specified doses; sham group: normal saline; and control group: no exposure. After six weeks, 3 ml blood samples were taken from the rats, and titrimetric and Ellman methods were used to assess serum and erythrocyte cholinesterase activity, respectively. The data was analyzed by SPSS 16, and p < 0.05 was considered significant.ResultsThe activities of serum and erythrocyte cholinesterase were inhibited significantly in the Malathion exposed group compared to the control group (p < 0.001). The administration of Vitamin C alone significantly increased the activities of serum and erythrocyte cholinesterase. The serum and erythrocyte cholinesterase inhibition showed improvement in the group that received both Malathion and Vitamin C.ConclusionMalathion reduced the activities of serum and erythrocyte cholinesterase in exposed animals. It probably has the same intoxication effects on people who are exposed. Improvement of cholinesterase activity by antioxidant effects of Vitamin C suggests that Vitamin C supplementation can be used to decrease side effects of OPP exposure.

Changes in the Number of Neurons in the Rat Motor Cortex and Movement Activity with Age

A programmable Laboras apparatus, consisting of an automated behavioral reaction recording system, was used to record movement activity in male rats aged one, eight, and 16 months studied in groups of 12, with subsequent determination of the numbers of neuron bodies in layer V of the motor cortex in preparations stained by the Nissl method. Different age groups were found to have different numbers of neurons in the motor cortex. The greatest number was seen in animals aged eight months. Movement activity correlated with the number of neurons.

Efecto de la lesión electrolítica del estriado dorsomedial sobre la conducta sexual y actividad locomotora de la rata

IntroductionCortical motor areas are influenced not only by peripheral sensory afferents and prefrontal association areas, but also by the basal ganglia, specifically the striatum. The dorsomedial striatum (DMS) and dorsolateral striatum are involved in both spatial and stimulus-response learning; however, each of these areas may mediate different components of learning. The aim of the study is to determine the effect of electrolytic lesion to the DMS on the learning and performance of sexual behaviour and locomotor activity in male rats. MethodOnce the subjects had learned to perform motor tests of balance, maze navigation, ramp ascent, and sexual behaviour, they underwent electrolytic lesion to the DMS. Five days later, the tests were repeated on 2 occasions and researchers compared performance latencies for each test. ResultsAverage latency values for performance on the maze and balance tests were higher after the lesion. However, the average values for the ramp test and for sexual behaviour did not differ between groups. ConclusionsElectrolytic lesion of the DMS modifies the performance of locomotor activity (maze test and balance), but not of sexual behaviour.

Eight hours of nocturnal 915 MHz radiofrequency identification (RFID) exposure reduces urinary levels of melatonin and its metabolite via pineal arylalkylamine N-acetyltransferase activity in male rats

Purpose: We investigated the effects of whole-body exposure to the 915 MHz radiofrequency identification (RFID) on mela-tonin biosynthesis and the activity of rat pineal arylalkylamine N-acetyltransferase (AANAT).Materials and methods: Rats were exposed to RFID (whole-body specific absorption rate, 4 W/kg) for 8 h/day, 5 days/week, for weeks during the nighttime. Total volume of urine excreted during a 24-h period was collected after RFID exposure. Uri-nary melatonin and 6-hydroxymelatonin sulfate (6-OHMS) was measured by gas chromatography-mass spectrometry (GC-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. AANAT enzyme activity was measured using liquid biphasic dif-13 fusion assay. Protein levels and mRNA expression of AANAT was 14 measured by Western blot and reverse transcription polymerase 15 chain reaction (RT-PCR) analysis, respectively.Results: Eight hours of nocturnal RFID exposure caused a sig-nificant reduction in both urinary melatonin (p = 0. 003) and 6-OHMS (p = 0. 026). Activity, protein levels, and mRNA expres-sion of AANAT were suppressed by exposure to RFID (p < 0. 05).Conclusions: Our results suggest that nocturnal RFID exposure can cause reductions in the levels of both urinary melatonin and 6-OHMS, possibly due to decreased melatonin biosynthesis via suppression of Aanat gene transcription in the rat pineal gland.

The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats

This study sought to investigate the effects of environmentally relevant gestational followed by continued chronic exposure to the herbicide, atrazine, on motor function, cognition, and neurochemical indices of nigrostriatal dopamine (DA) activity in male rats. Dams were treated with 100μg/kg atrazine, 10mg/kg atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning, male offspring continued daily vehicle or atrazine gavage treatments for an additional six months. Subjects were tested in a series of behavioral assays, and 24h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10mg/kg, this herbicide was found to produce modest disruptions in motor functioning, and at both dose levels it significantly lowered striatal DA and DOPAC concentrations. These results suggest that exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning.

Regulatory effects of dioxin-like and non-dioxin-like PCBs and other AhR ligands on the antioxidant enzymes paraoxonase 1/2/3.

Paraoxonase 1 (PON1), an antioxidant enzyme, is believed to play a critical role in many diseases, including cancer. PCBs are widespread environmental contaminants known to induce oxidative stress and cancer and to produce changes in gene expression of various pro-oxidant and antioxidant enzymes. Thus, it appeared of interest to explore whether PCBs may modulate the activity and/or gene expression of PON1 as well. In this study, we compared the effects of dioxin-like and non-dioxin-like PCBs and of various aryl hydrocarbon receptor (AhR) ligands on PON1 regulation and activity in male and female Sprague-Dawley rats. Our results demonstrate that (i) the non-dioxin-like PCB154, PCB155, and PCB184 significantly reduced liver and serum PON1 activities, but only in male rats; (ii) the non-dioxin-like PCB153, the most abundant PCB in many matrices, did not affect PON1 messenger RNA (mRNA) level in the liver but significantly decreased serum PON1 activity in male rats; (iii) PCB126, an AhR ligand and dioxin-like PCB, increased both PON1 activities and gene expression; and (iv) even though three tested AhR ligands induced CYP1A in several tissues to a similar extent, they displayed differential effects on the three PONs and AhR, i.e., PCB126 was an efficacious inducer of PON1, PON2, PON3, and AhR in the liver, while 3-methylcholantrene induced liver AhR and lung PON3, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent AhR agonist, increased only PON3 in the lung, at the doses and exposure times used in these studies. These results show that PCBs may have an effect on the antioxidant protection by paraoxonases in exposed populations and that regulation of gene expression through AhR is highly diverse.

The Effects of Perinatal Androgen Deprivation on Locomotor Activity in Male Rats

Testosterone and its metabolites—estrogen and dihydrotestosterone— are involved in the brain sex differentiation during the perinatal period by binding to androgen receptors (AR) or estrogen receptors (ER). However, in the presence of flutamide (FLU), testosterone that is metabolized to estrogen will only bind to ER. Blockade of AR using FLU during the perinatal period could alter the levels of estrogen, which in turn, may modulate the sex differentiation of the brain. This study tested perinatal androgen deprivation on estrogen levels and, in turn, its effects on locomotor activity in male rats.Long‐Evans rats (N=37) were divided into two groups: Group 1 received FLU (20 mg/kg; SC) during perinatal period (prenatal day 4 ‐ postnatal day 4) &amp; Group 2 served as control. On postnatal day 65, these groups were divided into 3 subgroups (injected 5 days/week x 7 weeks): A. finasteride (20 mg/kg, SC), an α‐reductase inhibitor, B. letrozole (2 mg/kg, SC), an aromatase inhibitor and C. vehicle.Open Field (OF) Paradigm: Each animal was tested every week in an OF apparatus where the rat was allowed to explore the OF for 6 minutes. The time spent in the center of the field was compared with the time spent in the periphery using Any‐Maze. In addition, serum estrogen levels were measured using ELISA.Animals receiving FLU not only had high serum estrogen levels but also showed increased locomotor activity by spending significantly more time in the center field. These results suggest that perinatal androgen deprivation results in high levels of estrogen that may contribute to their willingness to explore freely.