P-glycoprotein induction: an antidotal pathway for paraquat-induced lung toxicity

Dinis-Oliveira, Ricardo Jorge; Remião, Fernando; Duarte, José Alberto; Ferreira, Rita; Navarro, Amparo Sánchez; Bastos, Maria de Lourdes; Carvalho, Félix

doi:10.1016/j.freeradbiomed.2006.06.012

Cited by 78 publications

(55 citation statements)

References 64 publications

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“…Furthermore, various inflammatory mediators including TNF-␣ have been expected to be increased in the lung during PQ toxicity (Dinis-Oliveira et al, 2006a). It is known that TNF-␣ triggers the synthesis of leukotrienes and prostaglandin E (E 2 ) which then stimulate the infiltration of polymorphonuclear leukocytes into the lungs and cause lung injury (Dinis-Oliveira et al, 2006b).…”

Section: Discussionmentioning

confidence: 99%

The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats

Sun

Zhang²,

Yan³

et al. 2011

Environmental Toxicology and Pharmacology

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Section: Discussionmentioning

confidence: 99%

The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats

Sun

Zhang²,

Yan³

et al. 2011

Environmental Toxicology and Pharmacology

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“…P-gp inhibitors have been therapeutically used as a means to enhance accumulation of P-gp substrates in cancer cells, thus reverting the MDR phenotype associated to over-expression of P-gp (7,8). On the other hand, P-gp induction was proposed by our group as an antidotal pathway for P-gp substrates' induced toxicity, protecting cells from the toxic side effects of poisons (e.g., paraquat) (9,10).…”

mentioning

confidence: 99%

P‐glycoprotein activity in human Caucasian male lymphocytes does not follow its increased expression during aging

et al. 2011

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P-glycoprotein (P-gp) is a transmembrane protein that mediates the efflux of innumerous structurally unrelated compounds. It was initially found over-expressed in tumor cells, associated to a multidrug resistance phenotype (MDR). Then, P-gp was found constitutively expressed in excretory cells/tissues and in circulating cells, such as lymphocytes. Considering the importance of this transporter in the establishment of therapeutic protocols and the existence of contradictory results, this study aimed at evaluating the influence of aging in the expression and function of P-gp in human lymphocytes, comparing two different methodologies to assess both parameters. P-gp activity and expression were evaluated in lymphocytes isolated from whole blood samples of 65 healthy caucasian male donors, divided into two groups according to age (group 1: under 30-years old; group 2: above 60-years old). P-gp expression was assessed using the anti-P-gp monoclonal antibody, UIC2, in the presence and in absence of vinblastine (Vbl). P-gp activity was evaluated measuring the efflux rate of the fluorescent P-gp substrate rhodamine 123 (Rho 123) and also using UIC2 shift assay. Flow cytometric analysis was performed to assess all the proceedings. Furthermore, Pgp expression and each of the P-gp activity determination methods were compared, through correlation analysis and linear regression models. We observed a significant age-dependent increase in mean P-gp expression (p ¼ 0.029), which was not reflected in the transporter's activity (p > 0.050). Statistical analysis allowed selection of UIC2 shift assay over Rho 123 efflux assay as a more selective method to assess P-gp activity. Despite the significant correlation between P-gp expression and P-gp activity found in lymphocytes (Gp1(group 1)À Àr ¼ 0.609, p < 0.001; Gp2À Àr ¼ 0.461, p ¼ 0.012), using UIC2 shift assay, these data reinforce the need for P-gp activity assessment, rather than P-gp expression determination alone, when starting new therapeutic regimens with P-gp substrates, especially in men older than 60 years of age. ' 2011 International Society for Advancement of Cytometry Key terms P-glycoprotein; aging; UIC2 shift assay; Rho 123 efflux; flow cytometry P-GLYCOPROTEIN (P-gp), the product of multidrug-resistance 1 (MDR-1) gene in humans, is one of the most important and interesting members of the numerous, highly conserved, widespread membrane transporters of the ATP-binding cassette superfamily. It was first detected as a surface phosphoglycoprotein over-expressed in Chinese hamster ovary cultured cells selected for MDR, where it mediated resistance to many amphipathic drugs (1). Then, P-gp was also found constitutively expressed in epithelial cells from tissues with excretory function such as intestine, liver, kidneys, lungs, blood-brain barrier, and placenta, and also in blood cells such as lymphocytes (2), where P-gp expression may limit tissue penetration of its substrates. Thus, P-gp plays an important role in pharmacokinetics and pharmacodynamics of many

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“…TNF-α can trigger the synthesis of leukotriene and prostaglandin E2, stimulate the infiltration of granulocytes into the lungs, and cause lung injury. 35 IL-1β regulates the activity of helper T lymphocytes, the accumulation of chemotactic granulocytes, macrophages and lymphocytes, and mediates alveolar inflammation.…”

Section: Zhu Et Almentioning

confidence: 99%

Porous Se@SiO<sub>2</sub> nanospheres treated paraquat-induced acute lung injury by resisting oxidative stress

Zhu¹,

Deng²,

Ji³

et al. 2017

IJN

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Acute paraquat (PQ) poisoning is one of the most common forms of pesticide poisoning. Oxidative stress and inflammation are thought to be important mechanisms in PQ-induced acute lung injury (ALI). Selenium (Se) can scavenge intracellular free radicals directly or indirectly. In this study, we investigated whether porous Se@SiO 2 nanospheres could alleviate oxidative stress and inflammation in PQ-induced ALI. Male Sprague Dawley rats and RLE-6TN cells were used in this study. Rats were categorized into 3 groups: control (n=6), PQ (n=18), and PQ + Se@SiO 2 (n=18). The PQ and PQ + Se@SiO 2 groups were randomly and evenly divided into 3 sub-groups according to different time points (24, 48 and 72 h) after PQ treatment. Porous Se@SiO 2 nanospheres 1 mg/kg (in the PQ + Se@SiO 2 group) were administered via intraperitoneal injection every 24 h. Expression levels of reduced glutathione, malondialdehyde, superoxide dismutase, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α and interleukin-1β were detected, and a histological analysis of rat lung tissues was performed. The results showed that the levels of ROS, malondialdehyde, NF-κB, p-NF-κB, tumor necrosis factor-α and interleukin-1β were markedly increased after PQ treatment. Glutathione and superoxide dismutase levels were reduced. However, treatment with porous Se@SiO 2 nanospheres markedly alleviated PQ-induced oxidative stress and inflammation. Additionally, the results from histological examinations and wet-to-dry weight ratios of rat lung tissues showed that lung damage was reduced after porous Se@SiO 2 nanosphere treatment. These data indicate that porous Se@SiO 2 nanospheres may reduce NF-κB, p-NF-κB and inflammatory cytokine levels by inhibiting ROS in PQ-induced ALI. This study demonstrates that porous Se@SiO 2 nanospheres may be a therapeutic method for use in the future for PQ poisoning.

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P-glycoprotein induction: an antidotal pathway for paraquat-induced lung toxicity

Cited by 78 publications

References 64 publications

The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats

The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats

P‐glycoprotein activity in human Caucasian male lymphocytes does not follow its increased expression during aging

Porous Se@SiO<sub>2</sub> nanospheres treated paraquat-induced acute lung injury by resisting oxidative stress

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