Altering Cytochrome P4501a Activity Affects Polycyclic Aromatic Hydrocarbon Metabolism and Toxicity in Rainbow Trout (Oncorhynchus Mykiss)

Abstract

The polycyclic aromatic hydrocarbons (PAHs) phenanthrene and retene (7-isopropyl-1-methyl phenanthrene) are lethal to rainbow trout (Oncorhynchus mykiss) larvae during chronic exposures. Phenanthrene is a low-toxicity, non-cytochrome P4501A (CYP1A)-inducing compound that accumulates in fish tissues during exposure to lethal concentrations in water. Retene is a higher toxicity CYP1A-inducing compound that is not detectable in tissue at lethal exposure concentrations. The metabolism, excretion, and toxicity of retene and phenanthrene were examined in juvenile and larval rainbow trout during coexposure to the model CYP1A inducer beta-naphthoflavone (betaNF), or to the inducer-inhibitor piperonyl butoxide to determine if modulating CYP1A activity affected PAH metabolism and toxicity. Phenanthrene metabolism, excretion rate, and toxicity increased with coexposure to betaNE Piperonyl butoxide inhibited phenanthrene metabolism and reduced the excretion of all phenanthrene metabolites. As a consequence, embryo mortality rates increased but rates of sublethal effects did not. Coexposure of trout to retene and betaNF caused no change in retene metabolism and excretion, but retene toxicity increased, perhaps due to additivity. Piperonyl butoxide inhibited retene metabolism, decreased the excretion of some retene metabolites while increasing the excretion of others, and increased the toxicity of retene. These results support the role of CYP1A activity in PAH metabolism and excretion, and the role ofthe CYP1A-generatedmetabolites of PAHs in chronic toxicity to larval fish.

17β estradiol induced ROS generation, DNA damage and enzymatic responses in the hepatic tissue of Japanese sea bass

“…This might be due to E2 interaction with CYP1A metabolism pathways in sea bass hepatocytes through an inhibition of the EROD activity. Such effects Table 3 Correlation matrix for measured parameters in (a) fingerlings and (b) juveniles of Lateolabrax japonicus exposed to different concentration of E2 are of environmental concern, since this inhibition of CYP1A activity affects xenobiotic metabolism and toxicity (Hawkins et al 2002). Our data agreed with the earlier reports, since a reduction in EROD activity was observed in E2-treated fish, which was dose dependent.…”

Teratogenesis in Fundulus heteroclitus embryos exposed to a creosote-contaminated sediment extract and CYP1A inhibitors

“…Additionally, lowered embryo-toxicity as measured by DNA damage and medial yolk vein integrity has been shown in medaka (Orizias latipes) exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the presence of PBO (Cantrell, Lutz, Tillitt, & Hannink, 1996). However in a study by Hawkins, Billiard, Tabash, Brown, and Hodson (2002) researchers found increased toxicity in early life stage rainbow trout co-exposed to PAHs with PBO (Hawkins et al, 2002). In our study, inhibition of CYP1A activity by different inhibitors with several mechanisms of action enhanced the toxicity of ERSE, failing to support the original hypothesis.…”

A review on bioremediation of pulp and paper mill effluent – An alternative to conventional remedial technologies

“…Pulp and paper industry is one of the most polluting industries contributing 100 million kg of toxic pollutants every year in the environment (Dey et al, 2013). More than 260 chemicals have been identified in PPME which are produced at different stages of papermaking (Hawkins et al, 2002). The toxic nature is due to several naturally occurring and xenobiotic compounds which are formed and released during various stages of processing (Sharma et al, 2007).…”