Direct effect of p,p'- DDT on mice liver

Bárbara Arroyo-Salgado,Angélica Guerrero-Castilla,Jesús Olivero-Verbel

doi:10.1590/s1984-82502016000200007

Bárbara Arroyo-Salgado, Angélica Guerrero-Castilla + Show 1 more

Open Access

https://doi.org/10.1590/s1984-82502016000200007

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Abstract

ABSTRACT Contact with the pesticide dichlorodiphenyltrichloroethane (p,p′-DDT) can be the cause of various harmful effects in humans, wildlife, and the environment. This pesticide is known to be persistent, lipophilic, resistant to degradation, and bioaccumulive in the environment and to be slowly released into bloodstream. Growing evidence shows that exposure to DDT is linked to type 2 diabetes mellitus. Individuals exposed to elevated levels of DDT and its metabolite have an increased prevalence of diabetes and insulin resistance. To evaluate these possible relationships, experiments were performed on eight-week-old female mice, divided into three groups (n = 10 per group): Group 1 received a vehicle-control intraperitoneal (i.p.) injection of sesame oil; Groups 2 and 3 received an i.p. dose of 50 and 100 µg/g p,p′-DDT respectively, dissolved in sesame oil. All groups were treated once daily for four days. Real-time PCR analysis of several genes was undertaken. Additionally, biochemical parameters and histopathological changes were measured. NQO1, HMOX1, NR1I3 and NR3C1 were up-regulated in DDT-exposed animals compared to the vehicle control group, while only SREBP1 was down-regulated in the 100 µg/g group. MTTP and FABP5, not previously reported for DDT exposure, but involved in regulation of fatty acid fluxes, could also function as biomarkers cross-talking between these signaling pathways. These results suggest that beyond epidemiological data, there is increasing molecular evidence that DDT may mimic different processes involved in diabetes and insulin resistance pathways.

Highlights

Organochlorine pesticides (OC) were widely used in agriculture and pest control, but their use was banned during the 1970s and 1980s because of their high toxicity and environmental persistence
Compared to vehicle-control, significant up-regulation of mRNA expression was observed in the DDT-treated group (100 mg/kg) for oxidative stress responsive genes such as NAD(P) H dehydrogenase, quinone 1 (NQO1) (10.05 ± 3.00), peroxisome proliferator-activated receptor alpha (PPARα) (2.38 ± 0.57) and heme oxygenase decycling 1 (HMOX1) (2.21 ± 0.43), as well as in genes involved in fatty acid metabolism, including microsomal triglyceride transfer protein (MTTP) (1.95 ± 0.30) and fatty acid binding protein 5, epidermal (FABP5) (1.95 ± 0.28)
This may be a result of the activation of mouse-pregnane X receptor (PXR), while estrogen receptor (ER)-mediated effects were insignificant in rats, probably due to the inhibitory effects of constitutive androstane receptor (CAR) on ER activities

Summary

Introduction

Organochlorine pesticides (OC) were widely used in agriculture and pest control, but their use was banned during the 1970s and 1980s because of their high toxicity and environmental persistence. DDT has been extensively used worldwide to control malaria, typhus, body lice, and bubonic plague (ATSDR, 2002), but was banned in the United States by the Environmental Protection Agency in 1972, as a consequence of its potentially harmful effects on humans, wildlife, and the environment (Porta et al, 1999). It continues to be found frequently at high concentrations in human serum

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