Principles of Drug Action: The Basis of Pharmacology, Third Edition

Spratto, George R.

doi:10.1093/ajhp/48.1.175a

Cited by 2 publications

(7 citation statements)

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“…For example, more than 300 hepatic biotransformation enzymes have been described for the laboratory rat, Rattus norvegicus ( http://www.reactome.org , [ 13 ]). Enzyme activity assays exist for far fewer than the known number of biotransformation enzymes and are not always specific to a gene product [ 14 ]. To overcome these challenges, we took a genomic approach and used microarray technology customized for our study species, to identify, on a more global scale, biotransformation gene expression patterns involved in the processing of PSCs.…”

Section: Introductionmentioning

confidence: 99%

Evidence for functional convergence in genes upregulated by herbivores ingesting plant secondary compounds

2014

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BackgroundNearly 40 years ago, Freeland and Janzen predicted that liver biotransformation enzymes dictated diet selection by herbivores. Despite decades of research on model species and humans, little is known about the biotransformation mechanisms used by mammalian herbivores to metabolize plant secondary compounds (PSCs). We investigated the independent evolution of PSC biotransformation mechanisms by capitalizing on a dramatic diet change event—the dietary inclusion of creosote bush (Larrea tridentata)—that occurred in the recent evolutionary history of two species of woodrats (Neotoma lepida and N. bryanti).ResultsBy comparing gene expression profiles of two populations of woodrats with evolutionary experience to creosote and one population naïve to creosote, we identified genes either induced by a diet containing creosote PSCs or constitutively higher in populations with evolutionary experience of creosote. Although only one detoxification gene (an aldo-keto reductase) was induced by both experienced populations, these populations converged upon functionally equivalent strategies to biotransform the PSCs of creosote bush by constitutively expressing aldehyde and alcohol dehydrogenases, Cytochromes P450s, methyltransferases, glutathione S-transferases and sulfotransferases. The response of the naïve woodrat population to creosote bush was indicative of extreme physiological stress.ConclusionsThe hepatic detoxification system of mammals is notoriously complex, with hundreds of known biotransformation enzymes. The comparison herein of woodrat taxa that differ in evolutionary and ecological experience with toxins in creosote bush reveals convergence in the overall strategies used by independent species after a historical shift in diet. In addition, remarkably few genes seemed to be important in this dietary shift. The research lays the requisite groundwork for future studies of specific biotransformation pathways used by woodrats to metabolize the toxins in creosote and the evolution of diet switching in woodrats. On a larger level, this work advances our understanding of the mechanisms used by mammalian herbivores to process toxic diets and illustrates the importance of the selective relationship of PSCs in shaping herbivore diversity.

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Section: Introductionmentioning

confidence: 99%

Evidence for functional convergence in genes upregulated by herbivores ingesting plant secondary compounds

2014

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“…Isozymes of the monooxygenases like CYP 3A are involved in steroidegenesis whilst CYP 1A/2A and 2B sub-families metabolize ingested exogenous substances including drugs, leading to termination of their actions. Studies have shown that pre-treatment of rats with PB and 3-MC induced CYP 2B/2E and CYP 1A/2A/2E, respectively; thereby decreasing pentobarbital-induced sleeping or zoxazolamine-induced paralysis times (Pratt and Taylor, 1990). Other isozymes such as CYP 2E are of toxicological significance as it preferentially bioactivates hepatotoxic and carcinogenic substances to their reactive intermediates (Hoyumpa and Schenker, 1982;Wu and Cederbaum, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…Isozymes of the monooxygenases are targets for modulation by various medicines, including herbal medicines (Pratt and Taylor, 1990;Gyamfi and Aniya, 1998;Budzinski et al, 2000;Beckmann-Knopp et al, 2000) to cause significant drug interactions. ADD-199, in this study, did not alter the pentobarbital-induced sleeping and zoxazolamineinduced paralysis times.…”

Section: Discussionmentioning

confidence: 99%

“…In view of the chemical constituents identified in ADD-199 and the potential for chronic use of the extract to manage diabetes mellitus, there is need for its further investigation to determine its safety and potential for interaction with other drugs. Chronic use of some medications, including herbal medicines known to contain flavonol compounds may modulate cytochrome P450 (CYP) isozymes activities (Pratt and Taylor, 1990;Gyamfi and Aniya, 1998;Budzinski et al, 2000;BeckmannKnopp et al, 2000). These may precipitate interactions via metabolism and hence alter the duration of pharmacological effects of components in a multiple drug therapy (Pratt and Taylor, 1990).…”

Section: Introductionmentioning

confidence: 99%

“…Chronic use of some medications, including herbal medicines known to contain flavonol compounds may modulate cytochrome P450 (CYP) isozymes activities (Pratt and Taylor, 1990;Gyamfi and Aniya, 1998;Budzinski et al, 2000;BeckmannKnopp et al, 2000). These may precipitate interactions via metabolism and hence alter the duration of pharmacological effects of components in a multiple drug therapy (Pratt and Taylor, 1990). Therefore, in the present study, we determined the effects of ADD-199 on certain haematological, urinary and plasma biochemical parameters to assess its safety in male Wistar albino rats.…”

Section: Introductionmentioning

confidence: 99%

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