Isolation and some properties of dioxygenase and co-oxidase activities of adult human liver cytosolic lipoxygenase

Roy, Sandip Kumar; Kulkarni, Arun P.

doi:10.1002/(sici)1522-7146(1996)11:4<161::aid-jbt1>3.0.co;2-i

Cited by 15 publications

(9 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rodent embryonic LO activity can mediate this bioactivation of benzidine [93]. Purified LO from human term placenta [104], conceptal tissues at 10 weeks of gestation [98], adult human lung [136] and liver [137] also catalyze this reaction. Collectively, these results suggest that benzidine may be a developmental toxicant in man.…”

Section: Environmental Chemicalsmentioning

confidence: 99%

“…LO inhibitors and free radical scavengers markedly decrease the rate of SLO-mediated GS-PAP formation. Since significant LO activity occurs in rat [221] and human [137,147] liver as well as in rat embryo [93] and human conceptal tissues [96][97][98], in vivo teratogenic bioactivation of PAP by LO can be expected. In contrast to rat embryos which lack GST [222], human term placenta [223][224][225][226], human intrauterine conceptal tissues during early pregnancy (6-10 weeks gestation) [226] and human fetal liver (16-18 weeks gestation) [227][228][229][230] contain relatively high titer of this enzyme.…”

Section: Thiobenzamidementioning

confidence: 99%

See 1 more Smart Citation

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

Kulkarni

2001

CPD

View full text Add to dashboard Cite

Many developmental toxicants and teratogens require prior metabolism to reactive species or free radicals to exert toxicity. Thus the knowledge of conceptal biotransformation is absolutely critical in understanding toxicity of these chemicals. Due to extremely low content of cytochrome P450 in the embryo and other conceptal tissues, the research focus in recent years has steadily shifted toward enzymes capable of peroxidative oxidation of xenobiotics. At least three enzymes viz. lipoxygenase, peroxidase and prostaglandin synthase, each capable of peroxidative xenobiotic metabolism, occur in conceptal tissues of man and laboratory animals in biologically significant amounts. This review mainly summarizes the available information on the enzymatic bioactivation of teratogens and developmental toxicants belonging to diverse classes such as drugs, pesticides, environmental contaminants, industrial and other chemicals. Additionally, some discussion is devoted toward issues such as drug-drug interactions. The emerging new information on the peroxidative glutathione conjugate formation from xenobiotics is also presented. A critical need for gathering more information on this subject using different enzyme preparations from human conceptal tissues is stressed to avoid tragedies in the future.

show abstract

Section: Environmental Chemicalsmentioning

confidence: 99%

Section: Thiobenzamidementioning

confidence: 99%

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

Kulkarni

2001

CPD

View full text Add to dashboard Cite

show abstract

“…There is a great diversity of structures that can serve as substrates for hydroperoxidase activity of lipoxygenase and, as a consequence, it is of great interest to study the participation of the immobilized enzyme in the xenobiotic detoxification process. It has been reported that liver lipoxygenase possesses co‐oxidase activity, and this may represent another pathway, in addition to the cytochrome P450 pathway, for xenobiotic metabolism in liver [8]. On the other hand, the immobilization of cytochrome P450 has been reported, and the application of this system for environmental detoxification and biotransformation of drugs and pesticides has been proposed [9].…”

Section: Introductionmentioning

confidence: 99%

Chlorpromazine oxidation by hydroperoxidase activity of covalent immobilized lipoxygenase

Santano

Pinto

Macı́as

2002

Biotech and App Biochem

View full text Add to dashboard Cite

The application of the hydroperoxidase activity of immobilized lipoxygenase to xenobiotic metabolization is reported in this work. Soya bean lipoxygenase has been immobilized by covalent coupling to oxirane acrylic beads. This immobilized system has been applied to the oxidation of chlorpromazine (CPZ), a phenothiazine of wide pharmacological use which in some cases presents toxicity. Immobilized lipoxygenase produces the oxidation of CPZ in the presence of hydrogen peroxide at acidic pH, maintaining a high level of activity and stability. In comparison with free lipoxygenase, the immobilized enzyme system shows higher catalytic efficiency and protection against enzymic inactivation produced by the presence of H(2)O(2). When the system of immobilized enzyme was loaded into a bioreactor operating in continuous mode, the level of CPZ oxidation was higher than obtained using a discontinuous procedure or the free enzyme. The results obtained in this work suggest that a system of covalent immobilized lipoxygenase operating in continuous mode may constitute a valuable tool for xenobiotic detoxification or metabolization studies.

show abstract

“…In contrast to a relatively very low P450 content, LO is abundant in the rat brain (Byczkowski, Ramgoolie, and Kulkarni 1992;Naidu, Naidu, and Kulkarni 1992) and human placenta (Joseph, Srinivasan, and Kulkarni 1993;Datta and Kulkarni 1994;Datta, Sherblom, and Kulkarni 1997), the potential target tissues for imipramine toxicity. LO is also plentiful in the rat (Roy and Kulkarni 1994) and human liver (Roy and Kulkarni 1997). Furthermore, imipramine is freely soluble in water and sparingly soluble in organic solvents such as acetone (Merck Index 1976).…”

mentioning

confidence: 99%

Lipoxygenase-Mediated N-Demethylation of Imipramine and Related Tricyclic Antidepressants in the Presence of Hydrogen Peroxide

Sajan

Kulkarni

1999

Int J Toxicol

Self Cite

View full text Add to dashboard Cite

In this study, we examined the ability of soybean lipoxygenase to mediate the N-demethylation of imipramine and related drugs in the presence of hydrogen peroxide. Formaldehyde generation resulting from the N-demethylation of imipramine, a prototype drug, was found to depend on incubation time, and the concentration of the enzyme, imipramine, and hydrogen peroxide. Under optimal assay conditions, Vmax values of 14 to 18 nmol formaldehyde/min/nmol enzyme or 133 to 164 nmol formaldehyde/min/mg protein were observed. An inhibition of formaldehyde and desipramine formation by nordihydroguaiaretic acid con® rmed the lipoxygenase involvement. The blockade of the reaction by glutathione, dithiothreitol, butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) indicated the generation of a free radical intermediate from imipramine. Desipramine, trimipramine, clomipramine, and diltiazem, but not amitriptyline and doxepin, were also oxidized, albeit at a lower rate. Collectively, the evidence gathered in this study suggests, for the ® rst time, that tricyclic antidepressant drugs may undergo lipoxygenase-catalyzed N-demethylation.

show abstract

Isolation and some properties of dioxygenase and co-oxidase activities of adult human liver cytosolic lipoxygenase

Cited by 15 publications

References 50 publications

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals

Chlorpromazine oxidation by hydroperoxidase activity of covalent immobilized lipoxygenase

Lipoxygenase-Mediated N-Demethylation of Imipramine and Related Tricyclic Antidepressants in the Presence of Hydrogen Peroxide

Contact Info

Product

Resources

About