Gender difference in arsenic biotransformation is an important metabolic basis for arsenic toxicity

2021 ◽  
Author(s):  
Maihaba Muhetaer ◽  
Mei Yang ◽  
Rongxiang Xia ◽  
Jun Wu
Keyword(s):  
Gender Differences ◽  
Dose Group ◽  
Low Dose ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Arsenic Toxicity ◽  
Male And Female ◽  
Significant Difference ◽  
Medium Dose

Abstract Background: There are gender differences in the biotransformation of arsenic. We investigated the effects of gender differences on arsenic metabolism and arsenic toxicity mechanisms in rat liver tissues. Methods: Rats were treated with different amounts of arsenic compounds. Arsenic form MMA and DMA in the liver was determined by high performance liquid chromatography-hydride generation atomic fluorescence spectroscopy. SAM, ARR, NAD, PNP, PK, and MPO in rat liver were determined by enzyme-linked immunoassay. RT-qPCR was used to determine AS3MT in the liver. Results: Compared with male and female animals in the same group, MMA and DMA were statistically significant in the three groups of iAs3 + high, iAs3 + medium and iAs5+ low (P <0.05). The MMA of male rats in iAs3+ high and medium groups was higher than that of female rats, and the DMA of male rats was lower than that of female rats. As3MT mRNA in the male iAs3+ high group was higher than that of females. Besides, compared between male and female, only in iAS3+ low dose, iAS3+ medium dose, iAS5+ low dose, and iAS5+ medium dose groups, there was significant difference in SAM level (P<0.05). Compared with male and female animals in the same group, male rats had significantly higher PNP and ARR activities while lower PK activity than female rats (P<0.05). Between the male and female groups, only the iAS3+ high dose and medium dose group had a statistically significant difference (P<0.05). The NAD activity of females in iAS3+ high dose group was higher than that of males. Conclusion: Conclusively, under the same arsenic exposure, there were gender differences between female and male rats, and arsenic metabolism was more cytotoxic to male rats than to females.

Carcinogenesis Bioassay of Propyl Gallate in F344 Rats and B6C3FJ Mice

1983 ◽  
Vol 2 (6) ◽  
pp. 425-433 ◽  
Author(s):  
K. M. Abdo ◽  
J. E. Huff ◽  
J. K. Haseman ◽  
M. P. Dieter ◽  
G. A. Boorman ◽  
...  
Keyword(s):  
Propyl Gallate ◽  
Dose Group ◽  
Low Dose ◽  
Female Rats ◽  
Male Rats ◽  
High Dose Group ◽  
High Dose ◽  
Preputial Gland ◽  
Rats And Mice ◽  
F344 Rats

Chronic toxicity studies were conducted by maintaining groups of 50 F344 rats and 50 B6C3F1 mice of each sex on nutritionally complete diets containing 0%, 0.6%, or 1.2% propyl gallate for 103 weeks. Survival of rats and mice of both sexes was not significantly affected by the administration of this compound. Dosed rats and mice showed growth retardation and reduced feed utilization efficiency. Increased incidence of hepatic cytoplasmic vacuolization and suppurative inflammation of the prostate gland were observed in dosed male rats and were considered to be related to propyl gallate administration. Tumors of the preputial gland, islet ceil tumors of the pancreas, and pheochromocytoma of the adrenal gland were observed with significantly (p < 0.05) higher incidence in the low-dose male rats; however, there was little evidence of a dose response or of an effect in the high-dose group. Rare tumors (an astrocytoma and a glioma) were found in the brains of two low-dose female rats but none was found in the high-dose group. Malignant lymphoma occurred with a significant (p < 0.05) positive trend in male mice and the incidence in the high-dose group was significantly (p < 0.05) higher than that of the concurrent controls. However, the high-dose incidence was not significantly different from the historical control rate for the laboratory that conducted the bioassay. Under the conditions of the bioassay, propyl gallate was not considered to be clearly carcinogenic for F344 rats, although the increased incidence of preputial gland tumors, islet-cell tumors of the pancreas, and pheochromocytoma of the adrenal glands in low-dose male rats may have been related to compound administration. Thus, the evidence for carcinogenicity in male rats is regarded as being equivocal, while there was no indication of a carcinogenic response in female rats. Propyl gallate was not considered to be carcinogenic for B6C3F1 mice, although the increased incidence of malignant lymphoma in dosed male mice may have been related to administration of the test compound.

scholarly journals Possible mechanisms of the hypoglycaemic effect of artesunate: Gender implication

2020 ◽  
Author(s):  
Abdullateef Isiaka Alagbonsi ◽  
Toyin Mohammad Salman ◽  
Sheu Oluwadare Sulaiman ◽  
Adedini Kafayat ◽  
Susan Kebu
Keyword(s):  
Blood Glucose ◽  
Low Dose ◽  
Enzyme Activation ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Male And Female ◽  
G6pase Activity ◽  
Group I ◽  
High Doses

Abstract Background Artesunate is an antimalarial drug that affects glucose homeostasis but the mechanism of its glucose-modulating effect is not fully understood especially with gender implication, which is the information this study sought to provide. Methods Twenty-five (25) male and 25 female rats were separately and blindly allocated into five identical groups (n = 5/group). Group I (control) received 0.2 ml/kg distilled water. Groups II and III both received 2.90 mg/kg artesunate on day one, but 1.45 mg/kg from day two till day five and day fifteen respectively. Groups IV and V both received 8.70 mg/kg artesunate on day one, but 4.35 mg/kg artesunate from day two till day five and day fifteen respectively. Results In male rats, the blood glucose was reduced by low and high doses of artesunate at 5 days but increased by high dose at 15 days. Glucose was reduced in female rats but unchanged in male rats by low dose artesunate at 15 days. Artesunate increased glycogen concentration at short duration which normalised at long duration in both genders. Artesunate increased G6P concentration only in male rats at 15 days but reduced G6Pase activity in male and female rats (except in those that received low and high doses of artesunate for 15 days). Artesunate increased insulin only in male rats treated with low dose artesunate for 5 days. Artesunate increased cortisol concentration in male but reduced it in female rats. Artesunate decreased glucagon concentration except in female rats treated with high dose for 5 days. Artesunate increased oestrogen concentration in male rats that received low dose artesunate for 5 days but reduced it in female rats that received high dose for 15 days. Except in male rats that received high dose of artesunate for 15 days where testosterone was increased, artesunate did not affect testosterone concentration in all other male and female groups Conclusions The present study suggests that artesunate causes reduction in plasma glucose by reducing plasma glucagon concentrations and inhibiting liver glycogenolysis via inhibition of G6Pase activity in both sexes. In addition, increase in plasma insulin concentration contributed to the reduction in blood glucose caused by artesunate in male but not female rats; and artesunate-induced increase in G6P, a substrate for G6PD, could enhance NADPH generation and antioxidant enzyme activation in male rats.

scholarly journals Safety and efficacy of Edaravone Dexborneol versus edaravone for patients with acute ischaemic stroke: a phase II, multicentre, randomised, double-blind, multiple-dose, active-controlled clinical trial

2019 ◽  
Vol 4 (3) ◽  
pp. 109-114
Author(s):  
Jie Xu ◽  
Yilong Wang ◽  
Anxin Wang ◽  
Zhiqiang Gao ◽  
Xiaoping Gao ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Multiple Dose ◽  
Dose Group ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Score Change ◽  
Double Blind ◽  
Significant Difference ◽  
Medium Dose

BackgroundEdaravone Dexborneol is a novel neuroprotective agent that comprised edaravone and (+)-borneol, a food additive with an anti-inflammatory effect in animal ischaemic stroke models. This study aims to assess the safety and efficacy of Edaravone Dexborneol compared with edaravone in treating patients with acute ischaemic stroke (AIS).MethodsIn this multicentre, randomised, double-blind, multiple-dose, active-controlled, phase II clinical trial, patients with AIS within 48 hours after stroke onset were randomly assigned (1:1:1:1) to low-dose (12.5 mg), medium-dose (37.5 mg) or high-dose (62.5 mg) Edaravone Dexborneol groups, and an active control group with edaravone (30 mg) by 30 min intravenous infusion every 12 hours, for 14 consecutive days. The primary efficacy outcome was the proportion of modified Rankin Scale (mRS)score ≤1 at 90 days and National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 14 days after randomisation. The safety outcome included any adverse event during 90 days after treatment.ResultsOf 385 patients included in the efficacy analysis, 94 were randomised to low-dose group, 97 to medium-dose group, 98 to high-dose group and 96 to the control group. No significant difference was observed among the four groups on mRS score (mRS ≤1, p=0.4054) at 90 days or NIHSS score change at 14 days (p=0.6799). However, a numerically higher percentage of patients with mRSscore ≤1 at 90 days in the medium-dose (69.39%) and high-dose (65.63%) groups was observed than in the control group (60.64%). No significant difference in severe adverse events was found among the four groups (p=0.3815).ConclusionsCompared with edaravone alone, Edaravone Dexborneol was safe and well tolerated at all doses, although no significant improvement in functional outcomes was observed at 90days.Trial registration numberNCT01929096.

scholarly journals Pharmacokinetic and Histopathologic Study of an Extended-Release, Injectable Formulation of Buprenorphine in Sprague–Dawley Rats

2021 ◽  
Author(s):  
Barry L Levinson ◽  
Steven L Leary ◽  
Bev J Bassett ◽  
Charles J Cook ◽  
Gregory S Gorman ◽  
...  
Keyword(s):  
Dose Group ◽  
Extended Release ◽  
Low Dose ◽  
Test Group ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Time Points ◽  
Sprague Dawley Rats

A novel buprenorphine (BUP) extended-release formulation (BUP-XR) produced as a lipid-encapsulated, low viscosity BUP suspension for SC injection to control pain was evaluated for pharmacokinetics and safety in Sprague–Dawley rats given either 0.65 mg/kg (low dose) or 1.30 mg/kg (high dose). The 2 dosage groups each contained 6 male and 6 female rats to determine whether BUP-XR behaved differently in male or female animals. Blood samples were obtained from each animal before BUP-XR administration and at 6, 24, 48, 72, 96, and 168 h after administration. For necropsy and injection-sitehistopathology evaluation, 3 animals of each sex from each test group were euthanized on day 8, with the remaining animals euthanized on day 15. Mean plasma BUP concentration peaked from 6 to 24 h in all test groups, then declined in a linear fashion. Quantifiable plasma BUP was measured in all male rats at all time points except for one low dose group sample taken at 168 h. Female rats had quantifiable plasma BUP at all time points except for 1 low dose group sample at 72 and 96 h, and 2 low dose group samples at 168 h. The low dose groups, whether male or female, had lower mean plasma BUP levels at all time points as compared with their high dose counterparts, and female rats had lower mean plasma BUP levels than male rats at all time points. Results indicate that a single BUP-XR dose at either dose concentration can reliably provide plasma levels of BUP reported in the literature to be therapeutically relevant for up to 72 h, although lower plasma BUP levels can be anticipated in female rats compared with male counterparts. Mild to moderate injection-site granulomatous inflammation was observed in 6 of 12 rats in the low dose group and 7 of 12 in the high dose group. This reaction is characteristic of lipid material designed to persist in situ.

scholarly journals A clinical comparison of high dose and low dose of Suxamethonium

2014 ◽  
Vol 9 (2) ◽  
pp. 1-8
Author(s):  
RK Yadav ◽  
PC Majhi ◽  
D Tiwari
Keyword(s):  
Intraocular Pressure ◽  
Dose Group ◽  
Low Dose ◽  
Cardiovascular Responses ◽  
High Dose ◽  
Clinical Effects ◽  
Duration Of Action ◽  
Group I ◽  
Significant Difference ◽  
Group Ii

Background: Suxamethonium having its rapid onset and short duration of action makes this drug unique amongst the neuromuscular blocking drugs described so far. However, use of suxamethonium is associated with a large number of undesirable side effects. Objective: To evaluate clinical effects of high and low dose of suxamethonium and to determine whether lower dose of suxamethonium can be used for any beneficial effects in terms of its various adverse effects e.g. cardiovascular responses, post-operative muscle pains and intraocular pressure. Methods: A total of 100 patients were included in this prospective study. All these patients on preoperative clinical evaluation were assessed to have adequate airway. All the patients were divided in two groups, low dose group (group I) and High dose group (group II) with 50 patients in each at random. A standard anesthetic technique was adhered to all the patients and following parameters were observed on comparative basis: a. Fasciculation and post operative myalgia. b. Cardiovascular effects, c. Intraocular pressure. Observation: The incidence of post Suxamethonium pain was significantly greater in group II. Increase in heart rate from baseline was significant in both groups. There was no significant difference between the two groups in the diastolic pressure but rise in systolic blood pressure was significant at all assessment times in both groups. This rise from control was statistically significant. Conclusion: Suxamethonium can be used in lower doses (0.5 mg/kg) in elective cases without airway compromise. It gives benefits of reduced muscle pains, cardiovascular responses and intraocular hypertension. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-2, 1-8 DOI: http://dx.doi.org/10.3126/jcmsn.v9i2.9677

Male gender increases sensitivity to renal injury in response to cholesterol loading

2003 ◽  
Vol 284 (4) ◽  
pp. F718-F726 ◽  
Author(s):  
Diana M. Attia ◽  
Roel Goldschmeding ◽  
Mahmoud A. Attia ◽  
Peter Boer ◽  
Hein A. Koomans ◽  
...  
Keyword(s):  
Renal Injury ◽  
Low Dose ◽  
Plasma Cholesterol ◽  
A Priori ◽  
No Synthase ◽  
Male Gender ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Cholesterol Feeding

Males are at greater risk for renal injury than females. This may relate to nitric oxide (NO) availability, because female rats have higher renal endothelial NO synthase (NOS) levels. Previously, our laboratory found susceptibility to proteinuria induced by NOS inhibition in male compared with female rats. Dyslipidemia and hypercholesterolemia dose dependently decreased renal NOS activity and caused renal injury in female rats. We hypothesized that exposure of male rats to hypercholesterolemia would lead to more renal injury in male than in female rats due to an a priori lower renal NO system. Female and male rats were fed no, low-dose, or high-dose cholesterol for 24 wk. Cholesterol feeding dose dependently increased proteinuria in both female and male rats, but male rats developed more proteinuria at similar plasma cholesterol ( P < 0.001). Control males had lower renal NOS activity than control females (4.44 ± 0.18 vs. 7.46 ± 0.37 pmol · min−1 · mg protein−1; P < 0.05), and cholesterol feeding decreased renal NOS activity in males and in females ( P < 0.05). Cholesterol-fed males developed significantly more vascular, glomerular, and tubulointerstitial monocyte/macrophage influx and injury than females. Thus under baseline conditions, male rats have lower renal NOS activity than female rats. This may explain why male rats are more sensitive to renal injury by factors that decrease NO availability, such as hypercholesterolemia.

Influence of in utero di-n-hexyl phthalate and di-cyclohexyl phthalate exposure on the endocrine glands and T3, T4, and TSH hormone levels of male and female rats: Postnatal outcomes

2020 ◽  
Vol 36 (6) ◽  
pp. 399-416
Author(s):  
Nurhayat Barlas ◽  
Emre Göktekin ◽  
Gözde Karabulut
Keyword(s):  
Pituitary Gland ◽  
Dose Group ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Hormone Levels ◽  
Male And Female Rats ◽  
Endocrine Organs ◽  
Body Weights ◽  
Juvenile Stages

The present study was designed to evaluate the effects of di- n-hexyl phthalate (DHP) and di-cyclohexyl phthalate (DCHP) on endocrine organs in rats. Oil control, 20-, 100-, and 500 mg/kg dose groups were selected and administered to pregnant rats on gestational days 6–19 by oral gavage. The neonatal stages of rats continued until postnatal day 20 and the- juvenile stages of rats continued until postnatal day of 32. The rats were allowed to mature until the neonatal and juvenile stages and there after, they were divided into four groups corresponding to the treatment levels. Body and organ weights were recorded, serum was collected, and thyroid, pancreas, pituitary gland, and adrenal gland were removed. There was a decrease in body weights in the 20- and 500mg/kg DHP and in the 20-mg/kg DCHP dose groups in neonatal male rats. In contrast, for female rats, there was an increase in body weights in the 100-mg/kg DCHP dose group and there was a decrease in body weights in the 500-mg/kg DHP dose group. Body weights were increased at 20 and 500 mg/kg in the DHP-exposed juvenile male rats. Serum thyroid-stimulating hormone (TSH) levels were increased in neonatal male rats, while they were increased in the 100-mg/kg DHP group of neonatal and juvenile female rats. Serum triiodothyronine (T3) levels were increased at the high dose of DHP for neonatal male rats and at the low and high dose levels of DCHP for female rats. Serum thyroxine (T4) levels were increased in neonatal rats for DHP. Also, some histopathological changes were observed in the thyroid, pancreas, adrenal, and pituitary gland. In conclusion, it was shown that DHP and DCHP caused negative effects on T3, T4, and TSH hormone levels.

High-Dose Nadroparin Following Endovascular Aneurysm Treatment Benefits Outcome After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽  
2017 ◽  
Vol 83 (2) ◽  
pp. 281-287 ◽  
Author(s):  
Rene Post ◽  
IJsbrand A.J Zijlstra ◽  
Rene van den Berg ◽  
Bert A Coert ◽  
Dagmar Verbaan ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Dose Group ◽  
Low Dose ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Controlled Trial ◽  
Delayed Cerebral Ischemia ◽  
Neurological Status ◽  
High Dose ◽  
Aneurysm Treatment ◽  
Significant Difference

Abstract BACKGROUND Delayed cerebral ischemia (DCI) is one of the major causes of delayed morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE To evaluate the effect of high-dose nadroparin treatment following endovascular aneurysm treatment on the occurrence of DCI and clinical outcome. METHODS Medical records of 158 adult patients with an aSAH were retrospectively analyzed. Those patients treated endovascularly for their ruptured aneurysm were included in this study. They received either high-dose (twice daily 5700 AxaIE) or low-dose (once daily 2850 AxaIE) nadroparin treatment after occlusion of the aneurysm. Medical charts were reviewed and imaging was scored by 2 independent neuroradiologists. Data with respect to in-hospital complications, peri-procedural complications, discharge location, and mortality were collected. RESULTS Ninety-three patients had received high-dose nadroparin, and 65 patients prophylactic low-dose nadroparin. There was no significant difference in clinical DCI occurrence between patients treated with high-dose (34%) and low-dose (31%) nadroparin. More patients were discharged to home in patients who received high-dose nadroparin (40%) compared to low-dose (17%; odds ratio [OR] 3.13, 95% confidence interval [95% CI]: 1.36-7.24). Furthermore, mortality was lower in the high-dose group (5%) compared to the low-dose group (23%; OR 0.19, 95% CI: 0.07-0.55), also after adjusting for neurological status on admission (OR 0.21, 95% CI: 0.07-0.63). CONCLUSION Patients who were treated with high-dose nadroparin after endovascular treatment for aneurysmal SAH were more often discharged to home and showed lower mortality. High-dose nadroparin did not, however, show a decrease in the occurrence of clinical DCI after aSAH. A randomized controlled trial seems warranted.

scholarly journals Effectiveness of low dose versus high dose oxytocin regimen for induction of labour

2021 ◽  
Vol 10 (5) ◽  
pp. 1948
Author(s):  
Paridhi Gupta ◽  
Indu Chawla ◽  
Sonal Gupta
Keyword(s):  
Dose Regimen ◽  
Dose Group ◽  
Low Dose ◽  
Induction Of Labour ◽  
High Dose ◽  
High Dose Regimen ◽  
Nulliparous Women ◽  
Group I ◽  
Significant Difference ◽  
Group Ii

ABSTRACTBackground: Induction of labour is an indispensable part of modern obstetrics and certainly one of the most frequently performed obstetric procedure in the world. Oxytocin, being the most common inducing agent with multiple protocols being practiced, further research is required for the establishment of better protocol with optimal maternal and neonatal outcomes.Methods: Randomized comparative study including 100 term nulliparous women (randomized into high dose, group-I and low dose, group-II with 50 patients in each group) was done. High dose regimen was started with 4mu/min with increment of 4mu/min up to a maximum of 32mu/min and low dose regimen was started with 2mu/min with increment of 2mu/min up to a maximum of 32mu/min. Induction to delivery interval was the primary outcome. Secondary outcomes noted were rate of caesarean section, tachysytole with or without fetal distress, failed induction, maternal outcomes like need for instrumental vaginal delivery, PPH and choriamnionitis, neonatal outcomes like NICU admission, umbilical cord pH and apgar score.Results: There was significant reduction seen in induction to delivery interval among those induced with high dose oxytocin regimen. It was found to be 6.96±3.77 hours in group-I and 9.05±4.65 hours in group-II (p value 0.034). Though incidence of tachysystole was more in high dose regimen, it was not statistically significant. No significant difference was seen in secondary outcomes.Conclusions: On the basis of present study, high dose oxytocin regimen can be considered for induction of labour as it has same effects as that of low dose regimen with lesser induction to delivery interval.

scholarly journals Effect of Nalbuphine Combined With Intravenous Propofol for Anesthesia During Intestinal Endoscopic Submucosal Dissection in the Elderly

2021 ◽  
Author(s):  
Jingjing Liu ◽  
Biwei Zhan ◽  
Yongjun Zeng
Keyword(s):  
Endoscopic Submucosal Dissection ◽  
Dose Group ◽  
Total Duration ◽  
The Elderly ◽  
Neurocognitive Function ◽  
High Dose ◽  
Blood Oxygen Saturation ◽  
Submucosal Dissection ◽  
Significant Difference ◽  
Medium Dose

Abstract Objective: To investigate the effects of different doses of nalbuphine combined with an intravenous propofol pump for anesthesia during intestinal endoscopic submucosal dissection (ESD) in the elderly.Methods: A total of 85 elderly patients attending the Hanchuan People's Hospital from January 2016 to January 2018 were divided into low, medium, and high dose groups according to the intravenous dosing of nalbuphine given with a continuous propofol pump.The heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SaO2) were evaluated at five different time points (T1-T2).The levels of norepinephrine (NE), cortisol and blood glucose were intervals recorded. The occurrence of adverse reactions, hospitalization days, visual analogue scale (VAS) score, Ramsay sedation, and wake score after waking from anesthesia were assessed. Neurocognitive function was assessed at discharge and after surgery using the Montreal Cognitive Assessment (MoCA). Results: MR, MAP and SaO2 decreased significantly at T0-T4 in tested groups. The levels of NE, Cor, and Glu were significantly increased in three groups at T1-T3 and decreased among the medium-dose group. There was no statistically significant difference between the three groups in the total duration of anesthesia and the operative duration. The medium-dose group was performing significantly better than the low and high dose groups in clinical indicators. The postoperative VAS and Ramsay scores were higher in the low dose group (P＜0.05). There was a significant difference in neurocognitive function scores and no significant differences in postoperative anesthesia satisfaction and hospitalization days were observed amongst the three groups (P>0.05).Conclusions: The use of nalbuphine (0.1 mg/kg) combined with propofol for anesthesia during intestinal ESD in the elderly can shorten recovery times and reduce the incidence of postoperative adverse events and neurocognitive disorders.

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