Effects of piperonyl butoxide on exploratory behaviour in female mice

Previous studies reported that piperonyl butoxide (PBO) induces adverse effects on exploratory behaviour in male mice. However, no consistent effects of PBO treatment were observed in female mice. This study aimed to evaluate PBO’s neurobehavioral effects in female mice. Female mice were exposed to PBO through diet to provide levels of 0 (control), 0.025%, 0.1%, and 0.4% from 5 to 12 weeks of age, and selected behavioural parameters were measured. The average female body weight showed no significant effect from PBO treatment through the experimental periods. Regarding multiple-T water maze performance at 10 weeks of age, no significant effect caused by PBO treatment was observed. Exploratory behaviour examination of 8-week-old female mice indicated that the average speed declined in a significant dose-related manner, and the longitudinal pattern indicated a significant difference between the control and high-dose groups. For exploratory behaviour examination at 11 weeks of age, the total exploration distance shortened in a significant dose-related manner, and the average speed declined similarly. These longitudinal patterns showed significant differences between the control and high-dose groups. The PBO dose levels in this study produced several adverse effects on exploratory behaviour in female mice.

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Effects of piperonyl butoxide on spontaneous behavior in F1-generation mice

Toxicology and Industrial Health ◽

10.1177/0748233709346756 ◽

2009 ◽

Vol 25 (7) ◽

pp. 489-497 ◽

Cited By ~ 4

Author(s):

Toyohito Tanaka ◽

Osamu Takahashi ◽

Shinshi Oishi ◽

Akio Ogata

Keyword(s):

Dose Group ◽

Female Offspring ◽

Piperonyl Butoxide ◽

High Dose Group ◽

High Dose ◽

Adult Females ◽

Developmental Parameters ◽

Spontaneous Behavior ◽

Dose Levels ◽

F1 Generation

Piperonyl butoxide was given in the diet to provide levels of 0 (control), 0.02%, 0.06%, and 0.18% from 5 weeks of age of the F0 generation to 12 weeks of age of the F1 generation in mice. Select reproductive and neurobehavioral parameters were then measured. In exploratory behavior in the F0 generation, vertical time of adult females increased significantly in a dose-related manner. In behavioral developmental parameters, cliff avoidance was delayed significantly in the high-dose group in male offspring, and this effect was significantly dose-related. In female offspring, surface righting was significantly delayed in the high-dose group, and this effect was significantly dose-related. In spontaneous behavior in the F1 generation, females showed more activities in some variables in the high-dose group. Dose levels of piperonyl butoxide used in the present study produced several adverse effects in neurobehavioral parameters in mice.

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Lack of Neuropathological Changes in Rats Administered Tedizolid Phosphate for Nine Months

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03950-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 475-481 ◽

Cited By ~ 12

Author(s):

Michael J. Schlosser ◽

Hiromi Hosako ◽

Ann Radovsky ◽

Mark T. Butt ◽

Dragomir Draganov ◽

...

Keyword(s):

Body Weight ◽

Optic Nerve ◽

Body Weight Gain ◽

Maximum Tolerated Dose ◽

High Dose ◽

Once Daily ◽

Clinical Observations ◽

Activity Measures ◽

Dose Levels ◽

Neurobehavioral Effects

ABSTRACTTedizolid, a novel oxazolidinone antibacterial, was administered to Long Evans rats by oral gavage once daily for up to 9 months at doses near the maximum tolerated dose (MTD) to evaluate for potential neurotoxicity. Mean plasma exposures of tedizolid at the low-, medium-, and high-dose levels (7.5, 15, and 30 mg/kg of body weight/day for males; 2.5, 5, and 10 mg/kg/day for females) were similar between males and females and were 1.8-, 3.9-, and 8.0-fold greater than exposures in patients at the therapeutic dose (200 mg once daily). Evaluated endpoints included survival, clinical observations, body weight, and food consumption. At 1, 3, 6, and 9 months, ophthalmic examinations, functional observational batteries, and locomotor activity measures were conducted, brain weights/sizes were recorded, and perfusion-fixed tissues were collected from 12 rats/sex/group/time point. A detailed morphological assessment was conducted on brain, eyes, optic nerve/tract, spinal cord, peripheral nerves (includes sciatic, sural, tibial, peroneal, trigeminal), and skeletal muscle. At the end of 9 months, less body weight gain was seen in high-dose males (−6.7%) and females (−5.8%) compared with that seen in controls. There were no tedizolid-related adverse neurobehavioral effects or tedizolid-related histopathologic changes in the central/peripheral nervous systems, including the optic nerve. Results of this study indicate that tedizolid was not neurotoxic when administered long term to pigmented rats at doses near the MTD, which were up to 8-fold higher than the human therapeutic exposure.

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Maternal Vitamin D Deficiency Programs Reproductive Dysfunction in Female Mice Offspring Through Adverse Effects on the Neuroendocrine Axis

Endocrinology ◽

10.1210/en.2015-1638 ◽

2016 ◽

Vol 157 (4) ◽

pp. 1535-1545 ◽

Cited By ~ 10

Author(s):

Cari Nicholas ◽

Joseph Davis ◽

Thomas Fisher ◽

Thalia Segal ◽

Marilena Petti ◽

...

Keyword(s):

Vitamin D ◽

Adverse Effects ◽

Female Offspring ◽

In Utero ◽

Reproductive Physiology ◽

Gonadal Steroid ◽

Reproductive Dysfunction ◽

Control Female ◽

Female Mice ◽

Significant Difference

Abstract Vitamin D (VitD) deficiency affects more than 1 billion people worldwide with a higher prevalence in reproductive-aged women and children. The physiological effects of maternal VitD deficiency on the reproductive health of the offspring has not been studied. To determine whether maternal VitD deficiency affects reproductive physiology in female offspring, we monitored the reproductive physiology of C57BL/6J female offspring exposed to diet-induced maternal VitD deficiency at three specific developmental stages: 1) in utero, 2) preweaning, or 3) in utero and preweaning. We hypothesized that exposure to maternal VitD deficiency disrupts reproductive function in exposed female offspring. To test this hypothesis, we assessed vaginal opening and cytology and ovary and pituitary function as well as gonadotropin and gonadal steroid levels in female offspring. The in utero, preweaning, and in utero and preweaning VitD deficiency did not affect puberty. However, all female mice exposed to maternal VitD deficiency developed prolonged and irregular estrous cycles characterized by oligoovulation and extended periods of diestrus. Despite similar gonadal steroid levels and GnRH neuron density, females exposed to maternal VitD deficiency released less LH on the evening of proestrus. When compared with control female offspring, there was no significant difference in the ability of females exposed to maternal VitD deficiency to respond robustly to exogenous GnRH peptide or controlled ovarian hyperstimulation. These findings suggest that maternal VitD deficiency programs reproductive dysfunction in adult female offspring through adverse effects on hypothalamic function.

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Re-evaluation of neurobehavioural toxicity of clothianidin using statistical methods for ordered alternatives assuming dose-response effect

Toxicology and Industrial Health ◽

10.1177/0748233720979270 ◽

2020 ◽

pp. 074823372097927

Author(s):

Toyohito Tanaka

Keyword(s):

Statistical Methods ◽

Dose Response ◽

Dose Group ◽

Exploratory Behaviour ◽

High Dose Group ◽

High Dose ◽

Average Speed ◽

Ordered Alternatives ◽

Dose Response Effect ◽

Williams Test

Neurobehavioural toxicity of clothianidin in previous studies was re-evaluated using statistical methods for ordered alternatives assuming a dose-response effect. In a maternal exposure study, clothianidin was added into the diet to provide levels of 0% (control), 0.002%, 0.006% and 0.018% during the gestation and lactation periods in mice. In exploratory behaviour of male offspring in the F1 generation, average speed increased significantly in a dose-related manner in the Jonckheere test. Total distance lengthened in the high-dose group and average speed increased in the high-dose group in the Shirley–Williams test. In a two-generation toxicity study, clothianidin was added in the diet to provide levels of 0% (control), 0.003%, 0.006% and 0.012% from 5 weeks of age of the F0 generation to 11 weeks of age of the F1 generation in mice. The exploratory behaviour of adult males in the F0 generation, the average time of movement, and the number of rearing and rearing time increased significantly in a dose-related manner in the Jonckheere test. The average speed increased in the middle- and high-dose groups, number of rearing increased in the high-dose group and rearing time lengthened in middle- and high-dose groups in the Shirley–Williams test. These results suggest that the use of the appropriate statistical methods adjusted to the objectives of the study and the characteristics of the data could provide more definite conclusions.

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High Dose and Delayed Treatment with Bile Acids Ineffective in RML Prion-Infected Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00222-18 ◽

2018 ◽

Vol 62 (8) ◽

Author(s):

Grant Norman ◽

Jody Campeau ◽

Valerie L. Sim

Keyword(s):

Neurodegenerative Diseases ◽

Ursodeoxycholic Acid ◽

Bile Acids ◽

Cellular Prion Protein ◽

High Dose ◽

Prolonged Incubation ◽

Delayed Treatment ◽

Female Mice ◽

Significant Difference ◽

Incubation Periods

ABSTRACTPrion diseases are a group of neurodegenerative diseases associated with the misfolding of the cellular prion protein (PrPC) into the infectious form (PrPSc). There are currently no treatments for prion disease. Bile acids have the ability to protect hepatocytes from apoptosis and are neuroprotective in animal models of other protein-folding neurodegenerative diseases, including Huntington's, Parkinson's, and Alzheimer's disease. Importantly, bile acids are approved for clinical use in patients with cirrhosis and have recently been shown to be safe and possibly effective in pilot trials of patients with amyotrophic lateral sclerosis (ALS). We previously reported that the bile acid ursodeoxycholic acid (UDCA), given early in disease, prolonged incubation periods in male RML-infected mice. Here, we expand on this result to include tauro-ursodeoxycholic acid (TUDCA) treatment trials and delayed UDCA treatment. We demonstrate that despite a high dose of TUDCA given early in disease, there was no significant difference in incubation periods between treated and untreated cohorts, regardless of sex. In addition, delayed treatment with a high dose of UDCA resulted in a significant shortening of the average survival time for both male and female mice compared to their sex-matched controls, with evidence of increased BiP, a marker of apoptosis, in treated female mice. Our findings suggest that treatment with high-dose TUDCA provides no therapeutic benefit and that delayed treatment with high-dose UDCA is ineffective and could worsen outcomes.

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Does the radioactive iodine dose affect smell, taste sensation and nose function?

The Journal of Laryngology & Otology ◽

10.1017/s0022215120002571 ◽

2021 ◽

Vol 135 (1) ◽

pp. 50-56

Author(s):

B Tutar ◽

T Özülker ◽

G Berkiten ◽

S Karaketir ◽

M E Ekincioğlu ◽

...

Keyword(s):

Thyroid Cancer ◽

Adverse Effects ◽

Dose Group ◽

Differentiated Thyroid Cancer ◽

Radioactive Iodine ◽

High Dose ◽

Test Results ◽

Radioactive Iodine Therapy ◽

Significant Difference ◽

Iodine Dose

AbstractObjectiveTo detect whether the adverse effects of post-operative radioactive iodine therapy following differentiated thyroid cancer on smell, taste and nasal functions were associated with radioactive iodine dose.MethodsFifty-one patients who had undergone total thyroidectomy because of differentiated thyroid cancer were divided into two groups depending on the post-operative radioactive iodine therapy dose: low dose group (50 mCi; 21 patients) and high dose group (100–150 mCi; 30 patients). The Sniffin’ Sticks smell test, the Taste Strips test and the 22-item Sino-Nasal Outcome Test were performed on all patients one week before therapy, and at two months and one year following therapy.ResultsStatistically significant differences were detected in the Sniffin’ Sticks test results, total odour scores, total taste scores and Sino-Nasal Outcome Test results between the assessment time points. There was no statistically significant difference between the low and high dose groups in terms of odour, taste or Sino-Nasal Outcome Test scores either before or after therapy.ConclusionRadioactive iodine therapy has some short- and long-term adverse effects on nasal functions and taste and odour sensations, which affect quality of life. These effects are not dose-dependent.

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Dose-ranging evaluation of the serotonin antagonist dolasetron mesylate in patients receiving high-dose cisplatin.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.5.1045 ◽

1994 ◽

Vol 12 (5) ◽

pp. 1045-1049 ◽

Cited By ~ 57

Author(s):

M G Kris ◽

S M Grunberg ◽

R J Gralla ◽

L Baltzer ◽

S A Zaretsky ◽

...

Keyword(s):

Adverse Effects ◽

Intravenous Dose ◽

High Dose ◽

Single Intravenous Dose ◽

Complete Protection ◽

Complete Control ◽

Antiemetic Activity ◽

Dose Ranging ◽

Dose Levels ◽

Higher Doses

PURPOSE This dose-ranging trial of intravenous dolasetron mesylate (MDL73,147EF) was performed to determine its adverse and antiemetic effects in patients receiving cisplatin at doses > or = 100 mg/m2. PATIENTS AND METHODS Eighty-nine patients treated with initial cisplatin received a single intravenous dose of dolasetron mesylate administered over 20 minutes beginning 30 minutes before chemotherapy. The following four dose levels were studied: 1.8, 2.4, 3.0, and 5.0 mg/kg. Emesis and adverse effects were measured for 24 hours after cisplatin. RESULTS All adverse effects were mild and transient including loose stools, headache, serum AST/ALT elevations, and asymptomatic prolongation of ECG intervals. Among the dose levels, no-emesis rates from 24% to 52% were observed, and the percentage of patients having zero, one, or two emetic episodes ranged from 48% to 82%. Complete control of vomiting increased as the dose was escalated to 2.4 mg/kg, but did not improve further with higher doses. CONCLUSION Dolasetron mesylate can be administered safely at doses up to 5.0 mg/kg, with comparable complete protection rates and increased adverse effects at doses greater than 2.4 mg/kg. Antiemetic activity was seen after cisplatin. Trials comparing single infusions of dolasetron mesylate and ondansetron are under way.

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Decision letter for "Adverse effects of high‐dose vitamin D supplementation on volumetric bone density are greater in females than males"

10.1002/jbmr.4152/v2/decision1 ◽

2020 ◽

Keyword(s):

Vitamin D ◽

Bone Density ◽

Adverse Effects ◽

Vitamin D Supplementation ◽

High Dose ◽

Volumetric Bone Density ◽

High Dose Vitamin

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STUDIES ON SULFATION FACTOR (SF) ACTIVITY OF HUMAN SERUM

Acta Endocrinologica ◽

10.1530/acta.0.xxxv0381 ◽

1960 ◽

Vol XXXV (III) ◽

pp. 381-396 ◽

Cited By ~ 14

Author(s):

Sven Almqvist

Keyword(s):

Human Serum ◽

Normal Serum ◽

Treatment Level ◽

Response Curves ◽

Normal Children ◽

Significant Difference ◽

Human Sera ◽

Normal Humans ◽

Pre Treatment ◽

Dose Levels

ABSTRACT The sulfation factor (SF) activity of human sera has been estimated using a modification of the method of Daughaday et al. (1959). Each assay was statistically evaluated. The method had a mean precision of 0.14 and, used as an assay of GH of human serum, a sensitivity in three pituitary dwarfs of 0.1 to 0.6 μg of HGH/ml of serum. SF activity was found at all ages between 1 month and 75 years. There was a significantly lower mean SF activity below the age of half a year. Three cases of pituitary dwarfism had significantly low SF activities of sera. There was no significant difference between the SF activities of sera from untreated pituitary dwarfs and the sera from normal children below half a year of age. Dose-response curves with large volumes of sera from pituitary dwarfs and small volumes of sera from normal humans had the same slopes. Four mg of HGH prepared according to the method of Li & Papkoff (1956) resulted in a normal serum SF activity in each of the three dwarfs. A significant (P < 0.01) linear relationship was found between the concentration of SF activity of sera from these subjects and the logarithm of the dose of HGH given with dose levels of 1, 2 and 4 mg daily for three days. The decline of serum SF activity to the pre-treatment level following HGH in one dwarf suggested a half life not different from that indicated by others for growth hormone.

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