scholarly journals Effects of treatment with haloperidol and clozapine on the plasma concentrations of thyroid hormones in rats

2020 ◽  
Vol 54 (2) ◽  
pp. 71-76
Author(s):  
Afshin Samadi ◽  
Mojataba Ziaee ◽  
Selen Yilmaz Isikhan ◽  
Nuriye Nuray Ulusu ◽  
Mahshid Samadi
Keyword(s):  
Thyroid Hormones ◽  
Plasma Concentrations ◽  
Physiological Saline ◽  
Serum Levels ◽  
Control Group ◽  
Antipsychotic Treatment ◽  
High Dose ◽  
Mental Problems ◽  
Male Wistar Rats ◽  
Chemiluminescent Immunoassay

AbstractObjectives. Psychoactive drugs are group of compounds used to treat severe mental problems, including psychosis, as well as other conditions. This study assessed clinically relevant side effects of haloperidol and clozapine on the thyroid hormones.Methods. Haloperidol (0.05 and 2 mg/kg) or clozapine (0.5 and 20 mg/kg) was intraperitoneally injected to male Wistar rats for 28 days. The control group received 2 ml of physiological saline. A chemiluminescent immunoassay was used to measure the plasma levels of thyroid hormones.Results. Plasma concentrations of thyroxine (T4) in rats treated with high-dose (2 mg/kg) of haloperidol decreased significantly compared to the control group (p=0.001). However, both low (0.5 mg/kg) and high clozapine (20 mg/kg) doses did not have a significant effect on the plasma concentrations of T4 and triiodothyronine (T3) (p>0.05). Neither of the compound had a significant effect on T3 plasma concentration levels (p>0.05).Conclusions. Haloperidol and clozapine act via different mechanisms and may have dissociable effects on thyroid hormones. Following treatment with haloperidol, significant changes in T4, but not in T3, serum levels were observed. Haloperidol and clozapine had different effects on the thyroid hormone levels. These results indicate that antipsychotic treatment can contribute to the thyroid dysfunction. Therefore, greater caution should be applied to the antipsychotics use. The thyroid function of the patients should be closely monitored, while using these drugs.

scholarly journals Azathioprine and Methotrexate impaired the morphology and functions of the testes in adult wistar rats

2014 ◽  
Vol 31 (02) ◽  
pp. 075-081
Author(s):  
A. Akinlolu ◽  
O. Akinola ◽  
P. Khobe ◽  
K. Obasi ◽  
O. Dada
Keyword(s):  
Adult Male ◽  
Wistar Rats ◽  
Follicle Stimulating Hormone ◽  
Physiological Saline ◽  
Seminiferous Tubules ◽  
Control Group ◽  
Connective Tissues ◽  
Group I ◽  
Male Wistar Rats ◽  
Dose Dependent

Abstract Introduction: AAzathioprine and Methotrexate are both used in the treatment of cancer; and are classified as cytotoxic drugs with reported adverse effects such as oxidative damage to the DNA/RNA, the testes and sperm cells. This study, therefore, tested the hypothesis that AAzathioprine and Methotrexate administrations impair the morphology and functions of the testes in adult male wistar rats. Methods: AAzathioprine (50-150mg per day) and Methotrexate (2.5mg per week) are used in the treatment of cancer in adult Man. We tested the hypothesis that AAzathioprine and Methotrexate impair the morphology and functions of testes in rats. Forty adult male wistar rats (150-230g) were employed in the study: Control Group I received physiological saline while Experimental Groups II - V received oral administrations of 5mg/kg/bodyweight of AAzathioprine per day, 15mg/kg/bodyweight of AAzathioprine per day, 8mg/kg/bodyweight of Methotrexate per week and 20mg/kg/bodyweight of Methotrexate per week respectively for 35 days. Results: Histological examinations of the testes of rats of Groups II - V showed dose-dependent morphological anomalies such as fewer collagen ibers of connective tissues, disrupted seminiferous tubules and scanty spermatozoa when compared to rats of Group I. Statistical analyses showed dose-dependent elevated levels (P≤0.05) of superoxide dismutase and malondialdehyde in testes homogenates of rats of Groups II - V when compared to rats of Group I. This implied increased oxidative stress in rats of Groups II - V. Evaluations of Follicle Stimulating Hormone and Testosterone showed dose-dependent significantly elevated levels (P≤0.05) in rats of Groups II - V when compared to rats of Group I. Conclusions: Our findings are consistent with the stated hypothesis.

scholarly journals Quantitation, Absorption and Tissue Distribution of Coenzyme Q10 from Pak-wanban (Sauropus androgynus L. Merr.) Leaf and Its Antioxidant Activities

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Aikkarach KETTAWAN ◽  
Kansuda WUNJUNTUK
Keyword(s):  
Tissue Distribution ◽  
Coenzyme Q10 ◽  
Antioxidant Activities ◽  
Alpha Tocopherol ◽  
Control Group ◽  
High Dose ◽  
Cooking Oil ◽  
Supplement Group ◽  
Male Wistar Rats ◽  
Plasma Antioxidant

Pak-wanban (Sauropus androgynus L. Merr.), a popular Thai vegetable, has been found to have a high content of Coenzyme Q10 (CoQ10), which is a powerful antioxidant. This study investigated the quantitation, absorption and tissue distribution of CoQ10 from raw and stir-fried Pak-wanban and its antioxidant activities in rats. Male Wistar rats (seven weeks old) were randomly grouped as follows: (1) control, (2) raw Pak-wanban powder of 0.5 mg CoQ10/kg/day, (3) stir-fried Pak-wanban powder of 0.5 mg CoQ10/kg/day, (4) stir-fried Pak-wanban powder of 1.0 mg CoQ10/kg/day, and (5) commercially CoQ10 supplement groups of 0.5 mg CoQ10/kg/day. The results found that stir-fried cooking did not significantly reduce the content of CoQ10 in the Pak-wanban leaves. After 3 weeks of experimentation, the level of CoQ10 in the plasma, liver and spleen was increased in all Pak-wanban groups when compared to the control group. The level of CoQ10 in the stir-fried Pak-wanban group was significantly higher than the raw Pak-wanban group but slightly lower than the CoQ10 supplement group.  Liver alpha-tocopherol concentrations were markedly increased in rats that consumed a high dose of CoQ10 from stir-fried Pak-wanban of 1 mg of CoQ10/kg/day when compared with the control group. Plasma antioxidant activities (ORAC: FRAP: DPPH) were significantly increased in both groups of stir-fried Pak-wanban when compared with the control group. We concluded that CoQ10 in  Pak-wanban could be well absorbed and improved the plasma antioxidant activities. Furthermore, cooking oil may increase the bioavailability of CoQ10 from vegetables. Therefore, it would be useful for vegetarian people.

scholarly journals Quercetin Attenuates Pancreatic and Renal D-Galactose-Induced Aging-Related Oxidative Alterations in Rats

2020 ◽  
Vol 21 (12) ◽  
pp. 4348 ◽  
Author(s):  
Ali H. El-Far ◽  
Mohamed A. Lebda ◽  
Ahmed E. Noreldin ◽  
Mustafa S. Atta ◽  
Yaser H. A. Elewa ◽  
...  
Keyword(s):  
Body Weight ◽  
Physiological Saline ◽  
Basal Diet ◽  
Protective Role ◽  
Control Group ◽  
Functional Markers ◽  
Dependent Manner ◽  
Physiological Saline Solution ◽  
Male Wistar Rats ◽  
Bcl2 Protein

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-κB, IL-1β, and TNF-α), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.

P5330Evaluating lipid-lowering and anti-atherogenic effect of injectable curcumin in a rabbit model of atherosclerosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A A Momtazi-Borojeni ◽  
M Banach ◽  
M Majeed ◽  
A Sahebkar
Keyword(s):  
Low Dose ◽  
White Male ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Control Group ◽  
High Dose ◽  
Base Line

Abstract Background and purpose The present study was aimed to evaluate lipid-lowering and anti-atherogenic effect of an intravenous (IV) curcumin in the rabbit fed high cholesterol diet (HCD). Methods New Zealand white male rabbits (4–6 months old, n=25, weight 2.286±0.256 kg)were fed on a normal chow enriched with 0.5% (w/w) cholesterol for 5 weeks. Atherosclerotic rabbits were randomly divided into three group, including a control group receiving intravenous (IV) injection of saline buffer, two treatment groups receiving IV injection of curcumin at two different dosages, 1and 10 mg/kg/week, for 4 weeks. Blood samples were collected from fasted rabbits at pre- (week 5) and post-treatment (week 11) points for analysis of serum lipid levels, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglyceride (TG), and total cholesterol (TC). Aortic arch atherosclerotic lesions were assessed using hematoxylin and eosin (H&E) staining. Results To evaluate curcumin's effects on the hyperlipidemic states and atherosclerosis plaque, HCD-fed rabbits were weekly treated with the injectable curcumin at the low (1mg/kg/week) and high (10 mg/kg/week) doses by 4 weeks. At week 4 in compared with the control group, low-dose curcumin could reduce serum levels of LDL-c, HDL-c, TG, and TC by −6.22% ±1.77, −35.24% ±12.49, −29.84% ±10.14, −14.19% ±5.19, respectively. In the case of high-dose curcumin, serum levels of LDL-c, HDL-c, TG, and TC were changed by −44.36%±3.24, 14.05% ±6.39, −25.92% ±5.57, −56.59% ±10.22, respectively, when compared with the control group at week 4. Low-dose curcumin after 4 weeks' treatment could reduce serum levels LDL-c, HDL-c, TG, and TC up to 103±28 mg/dL, 18.33±4.66 mg/dL, 97.5±31 mg/dL, and 356.5±19.5 mg/dL, respectively, when compared with the base line levels (week 0). High-dose curcumin after 4 weeks' treatment could decrease serum levels of LDL-c, HDL-c, TG, HDL-c, and TC up to 207±17.04 mg/dL, 15.5±0.5 mg/dL, 333±40 mg/dL, and 514.5±22.23 mg/dL, respectively (Figure). H&E staining declared that atherosclerotic lesion grades were significantly lower in the curcumin-treated groups than the control group. Changes of lipids in rabbits on curcumin Conclusions The injectable curcumin at the low (1mg/kg) and high (10 mg/kg) could significantly improve dyslipidemia and alleviate atherosclerotic lesion in HCD-induced atherosclerotic rabbits.

scholarly journals Metabonomic Responses of Grazing Yak to Different Concentrate Supplementations in Cold Season

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1595
Author(s):  
Jia Zhou ◽  
Shuangming Yue ◽  
Quanhui Peng ◽  
Lizhi Wang ◽  
Zhisheng Wang ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Serum Levels ◽  
Rapeseed Meal ◽  
Cold Season ◽  
Supplementary Feeding ◽  
Control Group ◽  
Serum Metabolites ◽  
Treatment Groups ◽  
Group Serum ◽  
Highland Barley

Supplementation plays an important role in reversing the weight loss of grazing yaks during cold season. However, little is known about the effect of supplementation on the serum metabolites of grazing yaks. The objective of this study was to explore the effects of supplementary feeding on average daily gain (ADG) and serum metabolites with nuclear magnetic resonance (NMR)-based metabolomics method in growing yaks during cold season on the Qinghai-Tibetan plateau. Twenty 1.5-year-old female yaks (91.38 ± 10.43 kg LW) were evenly divided into three treatment groups and a control group (CON) (n = 5 per group). All the yaks were released to graze during daytime, whereas the yaks in the treatment groups were supplemented with highland barley (HLB), rapeseed meal (RSM), and highland barley plus rapeseed meal (HLB + RSM) at night. The whole experiment lasted for 120 days. Results indicated that the ADG of growing yak heifers was increased by concentrate supplementations, and ADG under HLB and HLB + RSM group was 37.5% higher (p < 0.05) than that with RSM supplementation. Supplementary feeding increased the plasma concentrations of total protein (TP), albumin (ALB), and blood urea nitrogen (BUN) of those in the CON group, and concentrations of BUN were higher in the RSM group than in the HLB and HLB + RSM group. Compared with the CON group, serum levels of glutamine, glycine, β-glucose were lower and that of choline was higher in the HLB group; serum levels of lactate were lower and that of choline, glutamate were higher in the HLB + RSM group. Compared with the HLB + RSM group, serum levels of glycerophosphoryl choline (GPC) and lactate were higher, and those of choline, glutamine, glutamate, leucine, N-acetyaspartate, α-glucose, and β-glucose were lower in the HLB group; serum levels of citrate, GPC and lactate were higher, and those of 3-Hydroxybutyrate, betaine, choline, glutamate, glutamine, N-acetylglycoprotein, N-acetyaspartate, α-glucose, and β-glucose were lower in the RSM group. It could be concluded that concentrate supplementations significantly improved the growth performance of growing yaks and supplementation with HBL or HLB plus RSM was better than RSM during the cold season. Supplementation with HBL or HLB plus RSM affected the serum metabolites of grazing yaks, and both treatments promoted lipid synthesis. Supplementation of yaks with HBL plus RSM could improve energy-supply efficiency, protein and lipid deposition compared with HLB and RSM.

scholarly journals The Efficacy of Once-Daily Dose of Phenobarbital in Children with Generalized Tonic-Clonic Epilepsy

2018 ◽  
Vol 35 (7-8) ◽  
pp. 172-9
Author(s):  
Amril A. Burhany ◽  
Sofyan Ismael ◽  
Hardiono Pusponegoro
Keyword(s):  
Clinical Trial ◽  
Plasma Concentrations ◽  
Serum Levels ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Study Group ◽  
Once Daily ◽  
Daily Dose ◽  
Plasma Measurements ◽  
Better Than

In spite of its long half life, phenobarbital is still given twice-daily in the treatment of generalized tonic-clonic epilepsy. This study aims to determine if daily dose of phenobarbital given once differs to that given twice daily. Subjects of this unblinded controlled clinical trial were generalized tonic-clonic epilepsy patients ranging in age from 1-15 years. There were 40 study cases and 42 controls. We gave phenobarbital 4-6 mg/kg/day once-daily for study group and twice-daily dose for control group. History, physical and EEG examination and phenobarbital plasma measurements were obtained a t the beginning of the study and four weeks later. The ratio of the second to first phenobarbital plasma concentrations in the study group was 0.99 while in the control group it was 1.02. The proportion of seizure-free patients in the study group increased from 70% at the beginning to 85% at the end of study, and in the control group from 64.3% to 83.3%. Hyperactivity and irritability increased in both groups, and there were no significant differences in mean serum levels, seizures control, hyperactivity and irritability in both groups. Drowsiness was found in 50% of cases, but statistically significant decrease were found in study group. The compliance of the study group (92.5%) was significantly better than that of the control group (71.4%).

Effect of human recombinant superoxide dismutase on canine myocardial infarction

1990 ◽  
Vol 258 (2) ◽  
pp. H369-H380 ◽  
Author(s):  
B. S. Patel ◽  
M. O. Jeroudi ◽  
P. G. O'Neill ◽  
R. Roberts ◽  
R. Bolli
Keyword(s):  
Superoxide Dismutase ◽  
Infarct Size ◽  
Low Dose ◽  
Coronary Occlusion ◽  
Plasma Concentrations ◽  
Control Group ◽  
High Dose ◽  
Collateral Flow ◽  
Tetrazolium Chloride ◽  
Arterial Blood

To determine whether human recombinant superoxide dismutase (h-SOD) produces sustained reduction of infarct size, anesthetized dogs underwent a 2-h coronary occlusion followed by either 48 or 4 h of reperfusion. In the 48-h study, dogs were randomized to three intravenous treatments: 1) “low-dose” h-SOD (2 mg/kg bolus 2 min before reperfusion followed by 4 mg/kg over 45 min), 2) “high-dose” h-SOD (8 mg/kg bolus 2 min before reperfusion followed by 8 mg/kg over 45 min), or 3) equivalent volumes of saline. In the 4-h study, dogs were randomized to high-dose h-SOD or saline. Occluded bed size was measured by postmortem perfusion and infarct size by triphenyl tetrazolium chloride staining and planimetry. Investigators performing the study and measuring infarct size were blinded to the treatment given. High plasma concentrations of h-SOD were present in the arterial blood of treated dogs in the early phase of reperfusion (greater than 60 and greater than 180 micrograms/ml in low- and high-dose groups, respectively). In both studies, control and treated groups were similar with respect to occluded bed size, collateral blood flow, and rate-pressure product during ischemia. In the 48-h study, infarct size, expressed as percent of occluded bed size, was 41.3 +/- 7.6% (mean +/- SE) in the control group, 37.1 +/- 7.2% in the low-dose h-SOD group, and 48.0 +/- 7.1% in the high-dose h-SOD group. In the 4-h study, infarct size was 30.6 +/- 4.9% in the control group and 31.5 +/- 9.6% in the high-dose h-SOD group. Analysis of the flow-infarct relationships confirmed that h-SOD did not reduce infarct size at any level of collateral flow in either the 48- or 4-h study. Recovery of regional myocardial function after reperfusion was also unaffected by h-SOD in both studies. Thus in this randomized blinded study, large doses of h-SOD given at the time of reperfusion failed to limit infarct size or enhance recovery of function, both early (4 h) and late (48 h) after reperfusion following a 2-h coronary occlusion.

scholarly journals Apigenin Attenuates Adriamycin-Induced Cardiomyocyte Apoptosis via the PI3K/AKT/mTOR Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Yu ◽  
Huirong Sun ◽  
Wenliang Zha ◽  
Weili Cui ◽  
Ling Xu ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cardiac Injury ◽  
Serum Levels ◽  
Mtor Pathway ◽  
Cardiomyocyte Apoptosis ◽  
Control Group ◽  
Limiting Factor ◽  
High Dose ◽  
Induced Apoptosis ◽  
Related Proteins

Treatment with Adriamycin (ADR) is one of the major causes of chemotherapy-induced cardiotoxicity and therefore is the principal limiting factor in the effectiveness of chemotherapy for cancer patients. Apigenin (API) has been shown to play a cardioprotective role. The present study examined the effect of API on ADR-induced cardiotoxicity in mice. Sixty male Kunming mice were randomly divided into 4 groups: a control group, ADR model group, low-dose API treatment group (125 mg·kg−1), and high-dose API treatment group (250 mg·kg−1). Blood samples were taken to evaluate a spectrum of myocardial enzymes. Cardiomyocyte apoptosis was measured using a TUNEL assay, and cardiomyocyte autophagy was observed using electron microscopy. Moreover, apoptosis-related proteins, such as Bax and Bcl-2, autophagy-related proteins, including Beclin1 and LC3B, and PI3K/AKT/mTOR pathway-related proteins were examined with western blot. Our results demonstrate that ADR caused an increase in the serum levels of cardiac injury markers and enhanced cardiomyocyte apoptosis and autophagy. API administration prevented the effects associated with ADR-induced cardiotoxicity in mice and inhibited ADR-induced apoptosis and autophagy. API also promoted PI3K/AKT/mTOR pathway activity in ADR-treated mice. In conclusion, API may have a protective effect against ADR-induced cardiotoxicity by inhibiting apoptosis and autophagy via activation of the PI3K/AKT/mTOR pathway.

Serum Free Light Chain (FLC) Measurement in Multiple Myeloma (MM) Patients (pts) Correlate with Known Monoclonal Paraprotein, Disease Stage and Therapy Response.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4907-4907 ◽  
Author(s):  
Monika Engelhardt ◽  
Daniel Räpple ◽  
Andreas Weis ◽  
Emanuel Bisse ◽  
Gabriele Ihorst
Keyword(s):  
Early Detection ◽  
Therapy Response ◽  
Clinical History ◽  
Serum Levels ◽  
Disease Stage ◽  
Control Group ◽  
High Dose ◽  
Normal Range ◽  
Monitoring Therapy ◽  
The Impact

Abstract So far, data based on small patient (pt) population suggest that the measurement of serum FLC from MM pts undergoing high-dose chemotherapy (HDCT) with stem cell transplantation (SCT) may be a sensitive marker for monitoring therapy success and for early detection of relapse. For further evaluation of the impact of FLCs on the assessment of treatment efficacy of standard- (ST) and HDCT with SCT, we performed a prospective analysis on serial serum specimens from 86 MM and 9 control pts. Measurement of FLC concentration was performed with the commercially available Freelite™ kit (Binding Site). For statistical analysis, pts’ clinical history, age at diagnosis, sex, current state of disease, karyotype and serum parameters, such as ß2-microglobulin, calcium levels and serum creatinine were evaluated. In the control group (NHL=6, AML=1, non-hematological disease=2), median concentrations of kappa(k)- and lambda(l)- FLC were 9.8 mg/l and 12.8 mg/l, respectively, corresponding to reference intervals for healthy individuals with normal kappa(k)/lambda(l)-ratios. In MM, 40 (46.5%) pts displayed kappa(k)-FLC levels above the upper range of 19mg/l, 26 (30%) had lambda(l)-FLC levels above the upper range of 26 mg/l and 9 pts (10.4%) had both elevated kappa(k)- and lambda(l)-FLC serum levels. An abnormal kappa(k)/lambda(l)-ratio was observed in 45 (52,3%) MM pts. Pts with a known kappa(k)-paraprotein (n=58) had a median FLC kappa(k)-concentration of 38 mg/l, but lambda(l)-FLC within the normal range. For pts with a known lambda(l)-paraprotein (n=27), reciprocal findings (76.4 mg/l for lambda(l)- vs kappa(k)-FLC in the normal range) were observed. Pts with responsive disease (CR, PR and SD) had both kappa(k)- and lambda(l)- FLC levels within the normal range, whereas newly diagnosed pts (ED) and those with PD had kappa(k)- FLC levels approx. 3-times the normal range, with lambda(l)- FLC levels at the upper limit of normal. Pts receiving ST as compared with HDCT had higher FLC levels. This is also observed in pts with amyloidosis, renal impairment or PD. Our results suggest that serum FLC assay allows monitoring of the therapy response and early detection of relapse. Determination of FLCs is also important, when evaluating new therapeutic substances, and for detection of prognostic patterns for better risk-based stratification of treatment.

scholarly journals The Effects of Formaldehyde on Cytochrome P450 Isoform Activity in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Min Xu ◽  
Huaqiao Tang ◽  
Qian Rong ◽  
Yuanli Zhang ◽  
Yinglun Li ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
High Dose ◽  
Blood Samples ◽  
Time Points ◽  
Indoor Pollutant ◽  
Carcinogenic Effects

Formaldehyde (FA) is an occupational and indoor pollutant. Long-term exposure to FA can irritate the respiratory mucosa, with potential carcinogenic effects on the airways. The effects of acute FA poisoning on the activities of CYP450 isoforms CYP1A2, CYP2C11, CYP2E1, and CYP3A2 were assessed by determining changes in the pharmacokinetic parameters of the probe drugs phenacetin, tolbutamide, chlorzoxazone, and testosterone, respectively. Rats were randomly divided into three groups: control, low FA dose (exposure to 110 ppm for 2 h for 3 days), and high FA dose (exposure to 220 ppm for 2 h for 3 days). A mixture of the four probe drugs was injected into rats and blood samples were taken at a series of time points. Plasma concentrations of the probe drugs were measured by HPLC. The pharmacokinetic parameters t1/2, AUC(0-t), and Cmax of tolbutamide, chlorzoxazone, and testosterone increased significantly in the high dose versus control group (P<0.05), whereas the CL of chlorzoxazone and testosterone decreased significantly (P<0.05). However, t1/2, AUC(0-t), and Cmax of phenacetin decreased significantly (P<0.05), whereas the CL of phenacetin increased significantly (P<0.05) compared to controls. Thus, acute FA poisoning suppressed the activities of CYP2C11, CYP2E1, and CYP3A2 and induced the activity of CYP1A2 in rats. And the change of CYP450 activity caused by acute FA poisoning may be associated with FA potential carcinogenic effects on the airways.

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