Induction of hepatic drug metabolizing enzymes in mammals by pesticides: A review

Abstract

The induction of drug metabolizing enzymes in mammals is summarized including both enzymes of the cytochrome P‐450‐dependent microsomal mixed function oxidase system and glutathione S‐transferases. Particular emphasis is placed on the role of pesticides as inducers, the early work being summarized while investigations carried out at North Carolina State University are considered in greater detail. Finally, the possible significance of induction is considered.     

Benzoic acid, a stimulant of odorant receptors of Bombyx mori, is rapidly metabolized to N-benzoylserine on the antennae

Summary. Benzoic acid is a known stimulant of olfactory receptor cells in trichoid sensilla on the antennae of adult females of Bombyx mori. Exposure of freshly excised antennae, from B. mori females and males, to vapours of [¹⁴C]-benzoic acid revealed that the adsorbed acid is rapidly metabolized (15% conversion in 10 s), suggesting the presence of a highly active enzymatic system. The major product could be identified as N-benzoylserine by use of [²H₅]-benzoic acid, and mass spectrometry linked to a gas chromatograph (GC-MS) or a liquid chromatograph (LC-MS), for analysis of the metabolites. The conjugation of benzoic acid with an amino acid apparently represents a novel mode for the rapid deactivation of odorant molecules. Received 26 March 2001.     

Uptake of cadmium into cells in culture∗

Cadmium has been recognized as pollutant of the environment for many years and numerous studies on its toxic effects have been carried out. Little, however, is known about its metabolic behaviour e.g. why the metal is accumulated so extremely rapidly into the organs of men and animals. Since the study of the individual metabolic steps is very difficult in vivo cell cultures may be used to obtain first indications of what happens in the whole animal.

We used CHO cells in monolayer culture to study the conditions under which the uptake of cadmium occurs. From serumfree medium the metal is accumulated rapidly in the cells. The uptake is inhibited very strongly by the presence of serum or albumin. Accumulation occurs against a concentration gradient and is dependent on the incubation temperature. Below 10°C no cadmium uptake is seen. Several substances which are known to affect cell metabolism have been used to influence cadmium accumulation. Neither inhibitors of energy production nor microtubule or microfilament disruptors showed any substantial effect. In contrast SH‐group blocking agents markedly reduced cadmium uptake.

The results show that cadmium uptake does not occur by passive diffusion but by some active mechanism.     

Thiram‐induced toxic liver injury in male sprague‐dawley rats

Abstract

A single i.p. dose (120 mg/kg) of thiram given to male Sprague‐Dawley rats caused a significant increase in the activity of SGOT and SGPT 24 hr post‐treatment indicating liver damage. A considerable diminution in the serum cholinesterase activity was also noted in the treated rats as against the control animals. Additional evidence for thiram‐induced liver toxicity is provided by the observation that there was approximately 50% inhibition of the activity of hepatic microsomal benzphetamine N‐demethylase with a concomitant decrease in the concentration of cytochrome P‐450, an important component of the mixed‐function oxidase system. Although not significant, hepatic glutathione levels were also depleted by thiram, probably making the liver susceptible to toxic injury.     

Effect of Agave attenuata extracts on detoxification enzymes of Biomphlaria alexandrina

The toxicity and rising costs of synthetic molluscicides have led to interest in compounds derived from locally growing plants that can be used as molluscicides. The aim of the present work was to study the effect of extracts of some Egyptian plants having lethal effect on snails of medical importance (Biomphlaria alexandrina) as well as on antioxidant and glutathione detoxification enzymes. Ethanolic extracts of locally growing plants Agave attenuata, Agave sislana, Phytolaca dodecandra and Euphorbia spllendens were applied as a contact poison to B. alexandrina, the intermediate host of Schistosoma mansoni. The LC₅₀ of A. attenuata, A. sislana, P. dodecandra and E. spllendens are 82, 101, 98 and 98 mg/L, respectively. Glutathione and the enzymes involved in protection of the snail from reactive oxygen species namely, glutathione peroxidase, glutathione reductase, glutathione S-transferase, catalase, gamma glutamyl transferase increased in the survival snails exposed to high concentrations of A. attenuata. Glucose-6-phosphate dehydrogenase indirectly affecting glutathione reductase and the oxidation, reduction of glutathione significantly decreased in snails exposed to A. attenuata extracts. Superoxide dismutase level tend to decrease in snails exposed to A. attenuata of action. In conclusion A. attenuata is preferable when compared with synthetic molluscicides. The enzymes involved directly or indirectly in protection mechanism of the snail against A. attenuata are mainly responsible for snails survival.     

Renewable Resources and Enzymatic Processes to Create Functional Polymers: Adapting Materials and Reactions from Food Processing

We are exploiting materials and concepts from food science to create functionalized, environmentally friendly derivatives of the biopolymer chitosan, a byproduct of seafood processing. Functional groups are grafted onto chitosan using tyrosinase, the enzyme responsible for food browning. The functionalizing groups studied include low-molecular-weight phenols derived from natural sources and high-molecular-weight proteins. The approach of using low-molecular-weight phenols to functionalize chitosan is illustrated with arbutin, a natural phenol found in pears. Results demonstrate that tyrosinase initiates reactions that lead to the conversion of arbutin–chitosan solutions into gels. These gels can be rapidly broken by treatment with the chitosan-hydrolyzing enzyme chitosanase, demonstrating that the chitosan derivatives remain biodegradable. We briefly review other studies in which low-molecular-weight natural phenols are enzymatically grafted onto chitosan to confer functional properties. The creation of co-polymers is illustrated by results in which tyrosinase is used to couple gelatin onto chitosan. Gelatin is a proteinaceous byproduct of meat production. The tyrosinase-generated gelatin–chitosan conjugates have been observed to offer interesting rheological and thermal properties. These results demonstrate the potential for using renewable resources and enzymatic processing to create environmentally friendly polymers with useful functional properties.     

A Quantitative Safety Assessment Model For Transgenic Protein Products Produced In Agricultural Crops

Transgenic plants are now being used to develop pharmaceutical and industrial products in addition to their use in crop improvement. Using confinement requirements, these transgenic plants are grown and processed under conditions that prevent intermixing with commodity crops. Regulatory agencies in the United States have provided guidance of zero tolerance of these new industrial crops with commodity crops. While this is a worthy goal, it is theoretically unattainable. In spite of the best containment practices, there is a potential risk using any system of production due to unforeseen incidences including natural disasters or exposure to workers. The precautionary principle has been used for numerous regulated articles in addressing the potential risks of new products and technology based on a risk assessment in similar situations. We present here a risk assessment model that could be used as a start to develop an accepted model for the industry. The model is based on current risk models used for other regulated articles, but adapted for these types of products. This could be used to determine action levels in the event of an unintended exposure or to ensure that detection or confinement methods are adequate to avoid risks. As an example, aprotinin, a therapeutic protein now being produced in maize, was evaluated for potential risk to humans using this model.     

Sulfur Metabolism in Polluted Sphagnum Peat Bogs: A Combined 34S–35S–210Pb Study

The size and isotopic behavior of sulfur pools in²¹⁰Pb-dated peat cores were investigated to obtain aninsight into retention mechanisms of pollutant S in twomountain-top peatlands of the Northern Czech Republic, CentralEurope. The bogs were situated 40 km apart in an area whichbetween the years 1985 and 1995 received as much as 130 kg Sha^-1 yr^-1 from the atmosphere. Vertical peataccretion was faster at Pod Jelení horou (JH) than atVelký moál (VM). Organic carbon-bonded S was themost abundant sulfur pool, constituting 77 and 65 wt. % at JHand VM, respectively. At JH both the S concentration maximumand the highest annual S deposition rate were displaceddownward by more than 20 years (from 1987 to the 1960s)indicating that the buried S is vertically mobile. At VM the Sconcentration was the highest in the topmost 2-cm section eventhough atmospheric S deposition peaked in 1987. Differentmechanisms of S isotope redistribution prevailed in thetopmost peat layers at JH, where a negative ³⁴Sshift occurred, and at VM, where a positive ³⁴Sshift occurred. Bacterial sulfate reduction was responsiblefor the negative ³⁴S shift at JH. One possibleexplanation of the positive ³⁴S shift at VM isrelease of ³²S-enriched products of mineralization duringpeat diagenesis. There was a strong positive correlationbetween the abundance of total and pyrite S along the profiles.The presence of pyrite S at VM (526 ± 60 ppm) suggestedthat even at VM bacterial sulfate reduction occurred. Ananaerobic incubation of JH peat indicated sulfate reductionrate of 600 nmol g^-1 day^-1. The turnover times forinorganic S pools were shorter than for the organic S pools.Cumulative S contents in the Czech peat bogs were found to besignificantly lower than in similar sites in the NortheasternU.S., even though the atmospheric S inputs were more thanthree times higher at the Czech sites. Possible causes of suchdiscrepancy are discussed.     

联苯代谢对微生物的生长胁迫及分裂抑制

以联苯/多氯联苯降解菌株R04（Rhodococcus sp.R04）和几种模式微生物为研究对象，利用高效液相色谱、荧光显微镜、扫描电子显微镜等分析微生物在联苯及其代谢物培养条件下细胞分裂和形态的变化.结果表明联苯及其代谢产物对红球菌R04和几种模式微生物细胞的分裂有抑制作用，并对部分微生物形态有影响.与前体-联苯及其代谢产物2-羟基-6-酮基-6-苯基-2，4-己二烯酸相比，2，3-二羟基联苯对G⁺、G^-细菌，或是酵母细胞分裂都有较强的抑制和形态的改变.2，3-二羟基联苯导致R.R04和缺陷型R.R04细胞形成不完整隔膜的比例增加；造成96.4%的大肠杆菌BL21细胞表面凹陷，胞质内容物流失，菌体体积缩小；导致枯草芽孢杆菌89.6%的细胞体积明显缩小；导致金黄色葡萄球菌基本没有细胞能形成完整的分裂隔膜；导致红酵母细胞能进行出芽生殖的比例从64.2%降低到19.3%，但对其细胞形态无明显改变.联苯代谢物2，3-二羟基联苯对红球菌R04及其它微生物细胞分裂和增殖的抑制作用比其前体-联苯强，建议在研究环境化合物与微生物互作时，应考虑环境化合物代谢的毒性效应.     

近红外长余辉纳米颗粒经小鼠眼部暴露后体内分布和代谢情况

为了研究纳米颗粒通过眼部暴露后进入体内的路径及在体内的分布和代谢情况,实验采用近红外长余辉纳米探针作为示踪剂,对小鼠进行眼部暴露,随后利用活体成像技术观察其进入小鼠体内的过程及分布情况,于暴露第4天收集代谢产物,第7天取重要脏器和血液,并检测纳米探针的存在情况.结果显示纳米探针可由眼经口腔进入胃肠道中,并且纳米颗粒暴露4天后在小鼠的粪便中检测到强荧光信号,而尿液中的荧光信号较弱,暴露7 d后在小鼠的眼睑结膜、胃及眼球中检测到强荧光信号,而其余器官的荧光信号较弱.这表明通过眼部暴露后,纳米颗粒主要分布在眼和消化系统中,最后大部分经消化系统代谢.