Bioenergetics-based matrix population modeling enhances life-cycle toxicity assessment of tilapia Oreochromis mossambicus exposed to arsenic

The objective of this study was to integrate a bioenergetics-based modeling approach into a population stage structure to enhance life-cycle toxicity assessments of the effects of waterborne arsenic (As) on the population dynamics of the tilapia Oreochromis mossambicus. The proposed mathematical model links a Leslie matrix population model and a universal ontogenetic growth model embedding the population-level growth rate and stage-specific modes of toxic action. We present data analyses of key parameters and distributions and discuss the processes of data capture and analysis and the impact of acute/chronic As toxicity responses on population-level effects. We employed a three-parameter Hill equation model to describe the relationship between tilapia whole-body burden and mortality in order to estimate the probability of stage-specific vital rate of survival. Using the DEBtox theory, we distinguished three modes of toxic action (MOA): direct effects on growth and indirect effects via maintenance and food consumption on inhibition by arsenic of the growth of a tilapia population. The asymptotic population growth rate decreased from lambda = 1.0027 for the control group to lambda = 0.9935 for tilapia population exposed to 4 microg mL(-1) As, indicating a potential risk of population intrinsic growth rates for tilapia exposed to higher levels of waterborne As. Our results estimated that an As concentration of 1.02 microg mL(-1) would cause a 50% reduction in the tilapia population. We found that the interplay between external stressors of waterborne As concentration and internally generated modes of action decreasing feeding in the juvenile stage and increasing the maintenance cost in the adult stage had a pronounced influence on the population stage structure of tilapia.     

Acute toxicity and bioaccumulation of arsenic in tilapia (Oreochromis mossambicus) from a blackfoot disease area in Taiwan

The general objective of our work was to determine the acute toxicity and bioaccumulation of arsenic (As) in tilapia (Oreochromis mossambicus) from the blackfoot disease (BFD) area in Taiwan. The average concentration of As in pond water ranged from 17.8 to 49 microg L(-1). Acute toxicity tests showed that the As concentration that caused toxicity to tilapia ranged from 69 060 microg As L(-1), in the 24-h toxicity test, to 28 680 microg As L(-1), in the 96-h toxicity test. We measured As concentrations in various tissues of tilapia to identify the affinities of tissues for As. Significant correlations were found among the As concentrations in all tissues. The highest bioconcentration factor (BCF) was found in the intestine (maximum value: 2270). The order of BCFs was: intestine > stomach > liver approximately gill > muscle. Arsenic concentrations in all tissues were allometric, negatively correlating with fish body weight [r(2) = 0.63 +/- 0.045 (mean +/- SE), p < 0.05]. Our results also revealed that As concentrations in muscle tissue were positively correlated with As accumulation in the viscera (r(2) = 0.85, p < 0.05). Significantly higher concentrations of As were obtained in the viscera of tilapia [12.65 +/- 10.17 microg g(-1) dry wt (mean +/- SD)] than in the muscle tissue (3.55 +/- 0.42 microg g(-1) dry wt). Our results suggest that a simple way of reducing the health risk associated with consuming tilapia is to trim and cook the fish properly, that is, removing the viscera of tilapia can greatly reduce the amount of As ingested and consequently reduce the health risks.     

Prediction of paraquat exposure and toxicity in clinically ill poisoned patients: a model based approach

Aims

Paraquat poisoning is a medical problem in many parts of Asia and the Pacific. The mortality rate is extremely high as there is no effective treatment. We analyzed data collected during an ongoing cohort study on self-poisoning and from a randomized controlled trial assessing the efficacy of immunosuppressive therapy in hospitalized paraquat-intoxicated patients. The aim of this analysis was to characterize the toxicokinetics and toxicodynamics of paraquat in this population.

Methods

A non-linear mixed effects approach was used to perform a toxicokinetic/toxicodynamic population analysis in a cohort of 78 patients.

Results

The paraquat plasma concentrations were best fitted by a two compartment toxicokinetic structural model with first order absorption and first order elimination. Changes in renal function were used for the assessment of paraquat toxicodynamics. The estimates of toxicokinetic parameters for the apparent clearance, the apparent volume of distribution and elimination half-life were 1.17 l h⁻¹, 2.4 l kg⁻¹ and 87 h, respectively. Renal function, namely creatinine clearance, was the most significant covariate to explain between patient variability in paraquat clearance.This model suggested that a reduction in paraquat clearance occurred within 24 to 48 h after poison ingestion, and afterwards the clearance was constant over time. The model estimated that a paraquat concentration of 429 μg l⁻¹ caused 50% of maximum renal toxicity. The immunosuppressive therapy tested during this study was associated with only 8% improvement of renal function.

Conclusion

The developed models may be useful as prognostic tools to predict patient outcome based on patient characteristics on admission and to assess drug effectiveness during antidote drug development.     

Acute toxicity and bioaccumulation of pesticide Diazinon in red tilapia (Oreochromis niloticus x Mossambicus albina)

Young red tilapias were exposed for 96 h to each one of 6 concentrations of the pesticide Diazinon in order to determine the pesticide's acute toxicity level. After the ascertaining the lethal concentration (LC50) at 96 h, a level 10 times lower was selected for the bioaccumulation study of the pesticide in male and female specimens exposed for 9 days. The elimination process was carried out for 10 days beginning right after the conclusion of the accumulation process. Analytical procedures were developed and used for the studies of acute toxicity and bioaccumulation of Diazinon in red tilapia. A lethal concentration [LC50 (96 h)] of 3.85 mg/L was found, and steady-state accumulation, at a concentration of 28.45 mg/kg, was reached at 7.72 days. In the elimination process a concentration of 0.29 mg/kg was found in tilapia tissue by the sixth day after the fish were moved to clean water, and it continued to decrease quickly toward nondetectable levels.     

A biotic ligand model-based toxicodynamic approach to predict arsenic toxicity to tilapia gills in cultural ponds

Farming of tilapia Oreochromis mossambicus is an important aquacultural activity in Taiwan. Due to the elevated arsenic (As) concentration in pond water, it is important to assess the bioavailability and toxicity of As to tilapia for protection of aquatic life and human health. In the present study, we developed a biotic ligand model (BLM)-based toxicodynamic approach to dynamically predict both acute and chronic effective concentrations of As to tilapia in two tilapia farms located at Pudai and Chiangchun counties in southwestern Taiwan. Parameters revealed in the mechanistic model were obtained by fitting this model to the toxicokinetic and toxicodynamic data from our previous laboratory experiments. Based on our extended BLM concepts, the site-specific water effect ratios and ambient water quality criteria can be determined with known water chemistry. The proposed methodology was capable of bridging the gap between laboratory toxicity bioassays and field investigations. With respect to risk assessments, our research may also provide an useful means of generating and adjusting the site-specific ambient water quality criteria.     

Developmental toxicity assessment of arsenic acid in mice and rabbits

To evaluate potential effects of exposure to inorganic arsenic throughout major organogenesis, CD-1 mice and New Zealand White rabbits were gavaged with arsenic acid dosages of 0, 7.5, 24, or 48 mg/kg/d on gestation days (GD) 6 through 15 (mice) or 0, 0.19, 0.75, or 3.0 mg/kg/d on GD 6 through 18 (rabbits) and examined at sacrifice (GD 18, mice; GD 29, rabbits) for evidence of toxicity. Two high-dose mice died, and survivors at the high and intermediate doses had decreased weight gains. High-dose-group fetal weights were decreased; no significant decreases in fetal weight or increases in prenatal mortality were seen at other dosages. Similar incidences of malformations occurred in all groups of mice, including controls. At the high dose in rabbits, seven does died or became moribund, and prenatal mortality was increased; surviving does had signs of toxicity, including decreased body weight. Does given lower doses appeared unaffected. Fetal weights were unaffected by treatment, and there were no effects at other doses. These data revealed an absence of dose-related effects in both species at arsenic exposures that were not maternally toxic. In mice, 7.5 mg/kg/d was the maternal No-Observed-Adverse-Effect-Level (NOAEL); the developmental toxicity NOAEL, while less well defined, was judged to be 7.5 mg/kg/d. In rabbits, 0.75 mg/kg/d was the NOAEL for both maternal and developmental toxicity.     

Effects of depuration on histopathological changes in tilapia (Oreochromis niloticus) after exposure to cylindrospermopsin

Cylindrospermopsin (CYN) is a highly water‐soluble cytotoxin produced by several species of freshwater cyanobacteria and it is considered the second most studied cyanotoxin worldwide. CYN acts as a potent protein and glutathione synthesis inhibitor, as well as inducing genotoxicity, oxidative stress and histopathological alterations. Studies concerning the depuration of cyanobacterial toxins in aquatic organisms, especially in fish, are of great interest for fish economy and public health, but are scarce in the case of CYN. This is the first study reporting the ability of depuration (3 ? 7 days) in reversing or ameliorating the histopathological lesions induced in liver, kidney, heart, intestines, and gills of tilapia (Oreochromis niloticus ) due to exposure by immersion to repeated doses of a CYN‐containing culture of A. ovalisporum for 14 days. The main histopathological changes induced by CYN were glucogenic degeneration and loss of the normal hepatic cord‐structure (liver), hyperemia, dilated Bowman's capsule and cellular tumefaction (kidney), myofibrolysis, hemorrhages and edema (heart), necrosis and partial loss of microvilli (gastrointestinal tract), and hyperemia and inflammatory cells infiltrates (gills). After 3 days of depuration, gills were totally recovered, while the liver, kidney, and gastrointestinal tract required 7 days, and longer depuration periods may be needed for a full recovery of the heart. In addition, the morphometric study indicated that depuration managed to reverse the affectation in the hepatocytes nuclear diameters and cross sections of the proximal and distal convoluted tubules induced in CYN‐exposed fish. In general, these results validate depuration as an effective practice for detoxification of fish contaminated with CYN. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1318–1332, 2017.     

Effects of chitosan nanoparticles on survival,growth and meat quality of tilapia,Oreochromis nilotica

Abstract

To evaluate the effect of dietary chitosan and chitosan nanoparticles on survival rate, growth performance and meat quality of tilapia (Oreochromis nilotica) under laboratory conditions, fish were fed with these compounds both at 5.0 g kg^-1 of diet for a period of 60 days. The addition of chitosan nanoparticles (T-2) significantly improved (P < 0.05) final weight, daily weight gain (DWG) and feed conversion ratio (FCR) compared to fish fed chitosan containing diet (T-1) and basal diet (control). However, there were no significant differences in final weight, DWG and FCR between T-1 and control. As for crude fat, the lowest content (P < 0.05) was found in T-2. In addition, a significant increase (P < 0.05) in inosinic acid content was found in T-2 compared with T-1 and control. These results indicate that dietary chitosan nanoparticles supplementation improved the growth performance and meat quality status of tilapia.     

Intersex tilapia (Oreochromis spp.) from a contaminated river in Taiwan: A case study

River pollution in Taiwan is rather serious, but so far there have been no reports of fish intersex problems. This report reveals that 50% male tilapia in the Era-Jiin River of southern Taiwan were found to be feminized in an October 8, 1994 collection from station EJ-2 of this river. After discounting all other possible causative factors, and correlating with endocrine disrupting chemicals found in this river, we suggest that there is a great possibility that the occurrence of intersex tilapia was caused by these chemicals. The above finding suggests that greater attention needs to be given to endocrine disrupting chemicals problems.     

Time‐dependent protective efficacy of Trolox (vitamin E analog) against microcystin‐induced toxicity in tilapia (Oreochromis niloticus)

Microcystins (MCs), hepatotoxins from cyanobacteria, induce oxidative stress and pathological changes in fish that can be ameliorated with chemoprotectants such as vitamin E (vit E). This study investigated the time period after MCs exposure in which Trolox, a vitamin E analog, is effective against oxidative and histological damage in different organs of tilapia (Oreochromis niloticus). Fish were fed Trolox supplement (700 mg/kg diet) for 7 days, or received only commercial fish food, and then were exposed to a single oral dose of 120 μg/fish microcystin‐LR, and sacrificed in 24, 48, or 72 h. The Trolox protective efficacy was evaluated based on lipid peroxidation (LPO), protein oxidation, enzymatic and non‐enzymatic antioxidants, and a morphologic study. Regarding the oxidative stress biomarkers altered by MCs, the higher protective action of Trolox was observed 24 h post toxin exposure, although it extends also until 48 h in gills (superoxide dismutase (SOD), catalase (CAT)), and liver, where glutathione reductase (GR) backed to control values 48 and 72 h after the toxin application. Glutathione‐S‐ transferase (GST) activity in the liver was ameliorated by the chemoprotectant after 24 and 48 h, although control values were not recovered. Trolox modulation of these biomarkers and its ability to quench free radicals explain the recovery of LPO values in all organs at 24 h and also in gills at 48 h. Histopathologically, Trolox efficacy was more evident after 72 h. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.     

The effects of maternal Cd on the metallothionein expression in tilapia (Oreochromis mossambicus) embryos and larvae

The purpose of this study was to identify the factor(s) which would enhance the Cd resistance as assessed by the metallothionein (MT) expression in tilapia larvae. Larvae were collected from parents that were pretreated respectively with Cd or saline. At the end of the 12-week experiment, the hepatic MT and Cd contents in the breeding female fish were recorded. Our results indicated that a significant relationship between Cd and MT contents can be found in the offspring from the parent fish treated with Cd. However, the higher Cd resistance, Cd contents, and MT expression were limited to those larvae from parent fish bred within 4 weeks of the injection. By week 12, the Cd-treated fish still contained high levels of MT in their hepatic tissues. However, the MT and Cd contents in the larvae from these adult fish were not significantly different from those from the controls. In summary, we suggest that the higher Cd resistance of larvae from the egg stage was a result of the Cd contamination of the parent female, as evidenced by an increase in MT expression induced in tilapia embryos and larvae.     

Vitamin E pretreatment prevents histopathological effects in tilapia (Oreochromis niloticus) acutely exposed to cylindrospermopsin

Cylindrospermopsin (CYN) is a cyanotoxin frequently involved in blooms with a predominantly extracellular availability, which makes it easily taken up by a variety of aquatic organisms. CYN is a potent protein and glutathione synthesis inhibitor, and also induces genotoxicity, oxidative stress and several histopathological lesions. The present study investigates the protective role of a vitamin E pretreatment (700 mg vit E/kg fish bw/day, for 7 days) on the histopathological alterations induced in different organs of tilapia (Oreochromis niloticus) acutely exposed to a single oral dose of 400 µg pure CYN/kg bw fish. The major histological changes observed were degenerative glucogenic process and loss of the hepatic structure in the liver, glomerulopathy and tubular tumefaction in the kidney, myofibrolysis and edema in the heart, catarrhal enteritis and necrosis in the gastrointestinal tract, hyperemic processes in the gill lamellae, and high basophilia, degeneration and tumefaction of granular neurons in the brain. Vitamin E pretreatment was effective in preventing or ameliorating the abovementioned alterations induced by CYN. In addition, a morphometric study indicated that the average nuclear diameter of hepatocytes, and cross‐sections of proximal and distal convoluted tubules, together with the cardiac fiber and capillaries diameters represent a useful tool to evaluate the damage induced by CYN. This is the first study reporting vitamin E prevention of histopathological damage in tissues (liver, kidney, heart, gastrointestinal tract, gills and brain) of fish intoxicated with CYN. Therefore, vitamin E can be considered a useful chemoprotectant in the treatment of histopathological changes induced in CYN‐intoxicated fish. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1469–1485, 2016.     

Protective role of dietary Spirulina platensis against diazinon-induced Oxidative damage in Nile tilapia; Oreochromis niloticus

The current study was performed to investigate the ameliorating effect of dietary supplementation of 0.5 and 1% Spiurolina platensis (SP) diet against the sub-acute toxicity of diazinon (DZN) 0.28 mg/L in Nile tilapia. At the end of experiment after 28 days, hepatic and renal damage markers (aspartate transaminase, alanine transaminase, alkaline phosphatase, urea, uric acid and creatinine), serum biochemical parameters (total proteins, albumin, cholesterol and glucose) and tissue antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione and malondialdehyde) were detesrmined. The results of the current study revealed significant improvement in hepatic and renal damage markers after SP supplementation in fish exposed to DZN toxicity. Moreover, SP improved serum biochemical markers through increasing serum albumin and globulins with a significant decrease in serum glucose and cholesterol. In addition, liver, kidneys and gills antioxidant status showed a significant improvement after SP supplemented to fish exposed to DZN where a significant increase in tissue antioxidant activity were observed with a significant decline in lipid peroxidation levels. It can be concluded that, SP supplementation attenuated the toxic effect of DZN toxicity in Nile tilapia through improving liver and kidney functions with a significant enhancement of tissue antioxidant status.     

Environmental exposure of arsenic and fluoride and their combined toxicity: A recent update

Environmental exposure to arsenic (As) and fluoride (F) in the recent year has been increased because of excessive use of naturally contaminated ground water. Surface water is also regularly contaminated with these elements in various industrial areas. Arsenicosis and fluorosis upon individual exposure of As and F are reported in many studies. A syndrome of endemic As poisoning and fluorosis occurs during concurrent exposure of As and F. Previous reports showed synergistic, antagonistic and independent effects of these two compounds, although few recent reports also revealed antagonistic effects after co-exposure. Interaction during intestinal absorption and influence of F on As metabolism might be the cause of antagonism. The synergism/antagonism is thought to depend on the dose and duration of the co-exposure. However, the detailed mechanism is still not fully understood and needs further studies. Removal technologies of As and F from contaminated water is available but removal of such contaminants from food is yet to be developed. Antioxidants are useful to mitigate the toxic effects of As and F. This review focused on the effect of co-exposure, amelioration as well as removal techniques of As and F.     

Effect of methomyl on sex steroid hormone and vitellogenin levels in serum of male tilapia (Oreochromis niloticus) and recovery pattern

Tilapia were exposed to sub‐lethal concentrations of 0, 0.2, 2, 20 or 200 μg/L for 30 days, then transferred to methomyl‐free water for 18 days. E₂, T, 11‐KTand VTG in serum were examined. There were no significant changes in all the parameters in serum of tilapia exposed to 0.2 μg/L and 2 μg/L methomyl compared to the control. However, 20 μg/L and 200 μg/L have the potential to disrupt the endocrine system of male tilapia, as shown by its ability to increase VTG and E₂ and decrease T and 11‐KT in serum. Thus it would appear the no observed adverse effect level for sexual steroid hormones of methomyl is lower than 2 μg/L. Recovery data showed that the effects produced by 20μg/L were reversible but not at 200μg/L. Furthermore, the sensitivity of above parameters to methomyl followed the order of VTG>E₂>11‐KT>T>GSI, suggesting VTG being the better biomarkers.     

Acute toxicity and bioaccumulation of arsenic in freshwater clam Corbicula fluminea

Arsenic is a potent human carcinogen of skin, lung, and urinary bladder. Freshwater clam Corbicula fluminea is a commercially important native species in Taiwan. C. fluminea is also a suitable biomonitoring test organism. Little is known, however, about the actual effects of arsenic on C. fluminea. The objectives of this study were to provide information on the acute toxicity and bioaccumulation kinetics of arsenic in C. fluminea. We carried out a 14-day exposure experiment to obtain bioaccumulation parameters. Uptake was very rapid when C. fluminea was first exposed and then slightly decayed during the uptake phase of the experiment and an uptake rate constant of 1.718 +/- 6.70 (mean +/- SE) mL g(-1) d(-1) was estimated. The elimination of arsenic from C. fluminea obeyed first-order depuration kinetics (r(2) = 0.85, p < 0.05) with a calculated half-life of 6.80 days. The derived bioaccumulation factor of 16.84 suggests that arsenic has a high potential for bioaccumulation in C. fluminea. This had important implications for dietary exposure of arsenic to humans who eat contaminated clams, because the soft tissue usually constitutes the majority of tissue consumed. The 96-h LC50 value was estimated to be 20.74 (95% CI: 11.74-30.79) mg L(-1) obtained from a 7-day acute toxicity bioassay. We also kinetically linked an acute toxicity model and a Hill sigmoid model to reconstruct an internal effect concentration based dose-response profile to assess the effect of soft tissue arsenic burden on the C. fluminea mortality. This result could be used to support the establishment of an ecological risk assessment to prevent possible ecosystem and human health consequences.     

Acute toxicity of intratracheal arsenic trioxide instillation in rat lungs

This study investigated the acute toxicity of different concentrations of arsenic trioxide (As₂O₃; ATO) on rat lungs. In total, 160 Wistar rats were randomly divided into the control, low‐, medium‐ and high‐dose groups, which were exposed to 0, 0.16, 1.60 and 16 μg/kg of ATO by intratracheal instillation, respectively. Samples were collected at 6, 12, 24, 48 and 72 hours after exposure and the dynamic changes indicative of acute lung toxicity were monitored. Compared with the control group, the exposure groups exhibited significant changes such as increased lung water content ratio and protein concentration in the bronchoalveolar lavage fluid, pulmonary interstitial thickening, cell membrane edema, increased inflammatory factor concentration, JNK and P38 were significantly activated, and the degree of phosphorylation was increased. Furthermore, all the changes in the exposure groups were exposure concentration‐dependent. ATO respiratory tract exposure can cause restrictive ventilatory disturbance in rats, and the degree of injury is exposure concentration‐dependent.     

Responses of glutathione‐related antioxidant defense system in serum of Nile tilapia (Oreochromis niloticus) exposed to sublethal concentration of methomyl and recovery pattern

Tilapia were exposed to sublethal concentrations of 0, 0.2, 2, 20, or 200 μg/L for 30 days, and then transferred to methomyl‐free water for 18 days. GST, GPx, GR, GSH, and GSSG in tilapia serum were examined at 0, 6, 12, 18, 24, and 30 days after methomyl exposure and at 18 days after transferring to methomyl‐free water. There were no significant changes in antioxidants activities and contents in serum of tilapia exposed to 0.2 μg/L. Significant increases in GST, GR, GPx, and GSSG accompanied by a decrease in GSH were observed following methomyl exposure to 2, 20, or 200 μg/L, suggesting the presence of oxidative stress. Thus, it would appear the 0.2 μg/L methomyl might be considered the no observed adverse effect level. Recovery data showed that the effects produced by lower concentration of 20 μg/L were reversible but not at the higher 200 μg/L concentration. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 483–489, 2015.     

Effects of low-level arsenic exposure on the developmental toxicity of anilofos in rats

In view of the increased use of anilofos for crop protection and ever increasing arsenic levels in drinking water in many countries, the coexistence of arsenic and anilofos in the environment is a reality and simultaneous exposure of humans and animals to these contaminants could be potentially hazardous. The aim of the present study was to examine whether coexposure to arsenic at the groundwater contamination level could alter the embryofetal toxicity of anilofos in rat model. Anilofos (100 mg kg(-1) day(-1)) and sodium arsenite (1 mg arsenic kg(-1) day(-1)) were administered by gavage either individually or in combination to the pregnant rats from day 6 to day 15 of gestation. Arsenic did not produce any significant effects either on maternal or fetal parameters at the given dose. Anilofos alone significantly decreased maternal weight gain, feed and water intakes, gravid uterine weights, number of live fetuses and fetal body weights and increased resorptions. There were increased incidences of gross, skeletal and visceral anomalies in the fetuses of anilofos-treated group. The main skeletal abnormality was increased intercostal space, while the visceral anomaly was an interventricular septal defect. Treatment with the combination of arsenic and anilofos significantly enhanced the fetal changes with much greater magnitude compared with the effects produced by anilofos alone. Anomalies such as midfacial cleft, exencephaly and anophthalmia were seen only in the fetuses of the combination group. The results show that anilofos interferes with embryofetal development and coexposure with arsenic at environmentally realistic concentrations produces additive or synergistic effects on the developmental toxicity of anilofos in rats.     

注射用伏立康唑前药在雌雄大鼠中代谢及毒性差异研究

目的：研究注射用伏立康唑前药（FLKZQY）在雌、雄大鼠中代谢及毒性差异,并观察SD大鼠体内性激素水平的变化对伏立康唑前药在大鼠体内代谢的影响,为其进一步临床应用提供依据。方法：选取5~6周龄SD大鼠,随机分成去势与伪手术组,雌、雄分开分组（雌、雄各半,每组8只）,手术后恢复3 d,然后连续7 d静脉注射120 mg·kg^-1·d^-1伏立康唑前药,于第7天进行眼眶采血。采用毒代动力学试验、酶联免疫吸附试验（ELISA）法,检测其代谢及毒性差异。结果：毒代动力学结果显示,伪手术雌鼠药时曲线下面积（AUC）、最大血药浓度（C_max）、半衰期（t_1/2）均高于伪手术雄鼠;去势雌鼠最大血药浓度（C_max）、半衰期（t_1/2）均较伪手术雌鼠显著性降低（P<0.05）,药时曲线下面积（AUC）极其显著性降低（P<0.01）;去势雄鼠受试物组与伪手术雄鼠受试物组相比药时曲线下面积（AUC）、半衰期（t_1/2）、最大血药浓度（C_max）则升高,其中AUC与C_max差异显著（P<0.05）;ELISA结果显示中,与伪手术雌鼠相比,去势雌鼠的肝脏细胞色素P450同工酶CYP2C19、CYP2C9以及CYP3A4含量均明显增加（P<0.05）,去势雄鼠与伪手术雄鼠相比P450同工酶含量降低,但未达到统计学差异。结论：在本试验条件下,注射用伏立康唑前药在雌、雄大鼠体内的代谢存在性别差异。而性激素水平可能通过调节伏立康唑相关代谢酶水平从而对伏立康唑代谢产生影响。