Effect of oxidative stress on expression and function of human and rat organic anion transporting polypeptides in the liver

Tsujimoto, Takashi; Ogura, Jiro; Kuwayama, Kaori; Koizumi, Takahiro; Sasaki, Shunichi; Terada, Yayoi; Kobayashi, Masaki; Yamaguchi, Hiroaki; Iseki, Ken

doi:10.1016/j.ijpharm.2013.10.013

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…Human OATP1B1 is expressed on the basement outer membrane of the hepatocyte membrane, and has a homologous transporter oatp1b2 in rat liver cells. There is a high degree of homology between human and rat liver transporters and studies in rat can be references for studies in human 27,28 . However, the alteration of OATPs expression did not completely parallel between human and rat primary hepatocytes, and there is no strict one-to-one relationship between human OATPs genes and rodent OATPs genes 29 .…”

Section: Discussionmentioning

confidence: 99%

Scutellarin inhibition of the rosuvastatin uptake in rat hepatocytes and the competition for organic anion transporting polypeptide 1B1 in HEK293T cells

Liu

Guo²,

Liu³

et al. 2020

Sci Rep

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www.nature.com/scientificreports www.nature.com/scientificreports/ by hepatocytes 13 . However, the mechanism of OATP1B1 involvement remains unclear, or whether scutellarin and rosuvastatin compete for OATP1B1. Therefore, in this study, we treated rats with rosuvastatin alone, or with a combination of rosuvastatin and a series concentration of scutellarin, to examine the plasma and hepatic levels of rosuvastatin in rats, as well as in OATP1B1 transfected HEK293T cells. Materials and MethodsAnimals. A total of 48 healthy male Sprague-Dawley rats weighing 230-270 g were obtained by the Experimental Animal Center of Nanchang University Medical College. Animals were housed in individual cages in an air-conditioned room at room temperature of 25 ± 1 °C with a 12 h light: 12 h dark period. The study was approved by the Ethical Committee of JiangXi Medical College, and all experiments were carried out with humane care according the Animal Care and Use Committee (ACUC) of Nanchang University Medical College. Rats were given free access to drinking water, after experiments, rats were euthanized by intraperitoneal injection of sodium pentobarbital with a dose of 200 mg/kg. Treatment and sampling. The rats were randomly divided into two groups with 24 rats in each group: the rosuvastatin group (rosuvastatin 10 mg/kg) and the combination treatment group (rosuvastatin 10 mg/kg + scutellarin 50 mg/kg), the concentrations used in the animal were transformed from clinical dose. The treatment was administered by gavage in the morning before feeding, and scutellarin was administered immediately following the rosuvastatin administration for the combination treatment group. In each group, 6 rats were maintained throughout the study and used for orbital vein blood sampling (0.15 ml) at 0 (before), 0.5, 1.0, 1.5, 2.0, 3.0, 5.0, 8.0, 12.0, 18.0, 24.0 h post treatment, to obtain the concentration-time profile data. Six of the remaining rats in each group were sacrificed at 1 h, 2 h, and 6 h post treatment (each time point) to sample the 0.5 ml of eyeball blood and the liver tissues. Blood was stored in heparinized tubes and the plasma was separated by centrifugation, then stored at −80 °C for further analysis. Scientific RepoRtS |(2020) 10:1308 | https://doi.

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Section: Discussionmentioning

confidence: 99%

Scutellarin inhibition of the rosuvastatin uptake in rat hepatocytes and the competition for organic anion transporting polypeptide 1B1 in HEK293T cells

Liu

Guo²,

Liu³

et al. 2020

Sci Rep

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“…Although mRNA levels of Oatp1a1, Oatp1b2 and Oatp2b1 were decreased at 6 h after intestinal I/R, these protein levels in intestinal I/R rats were same as those in sham-operated rats. The decreases in Oatps expression levels by ROS were recovered with time, though mRNA levels were still decreased (25). These findings also suggested that ROS mainly caused the decreases in Oatp1a1 and Oatp2b1 expression levels after intestinal I/R.…”

Section: Discussionmentioning

confidence: 68%

“…Thus, the production of ROS during ischemia and early stage of reperfusion may cause the alteration of Oatp1a1 and Oatp2b1 protein expression, as well as those of mRNA. Indeed, ROS are known to decrease Oatps expression (25). Although mRNA levels of Oatp1a1, Oatp1b2 and Oatp2b1 were decreased at 6 h after intestinal I/R, these protein levels in intestinal I/R rats were same as those in sham-operated rats.…”

Section: Discussionmentioning

confidence: 88%

Intestinal Ischemia-Reperfusion Suppresses Biliary Excretion of Hepatic Organic Anion Transporting Polypeptides Substrate

Maruyama¹,

Ogura²,

Fujikawa³

et al. 2013

J Pharm Pharm Sci

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-Purpose. Intestinal ischemia-reperfusion (I/R) causes gut dysfunction and promotes multi-organ failure. The liver and kidney can be affected by multi-organ failure after intestinal I/R. Organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) are recognized in a broad spectrum from endogenous compounds to xenobiotics, including clinically important drugs. Therefore, it is important for understanding the pharmacokinetics to obtain evidence of alterations in OATPs and OATs expression and transport activities. In the present study, we investigated the expression of rat Oatps and Oats after intestinal I/R. Methods. We used intestinal ischemia-reperfusion (I/R) model rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Plasma concentration and biliary excretion of sulfobromophthalein (BSP), which is used as a model compound of organic anion drugs, were measured after intravenous administration in intestinal I/R rats. Results. Although Oat1 and Oat3 mRNA levels were not altered in the kidney, Oatp1a1, Oatp1b2 and Oatp2b1 mRNA levels in the liver were significantly decreased at 1-6 h after intestinal I/R. Moreover, Oatp1a1 and Oatp2b1 protein expression levels were decreased at 1 h after intestinal I/R. Plasma concentration of BSP, which is a typical substrate of Oatps, in intestinal I/R rats reperfused 1 h was increased than that in sham-operated rats. Moreover, the area under the concentration-time curve (AUC0-90) in intestinal I/R rats reperfused 1 h was significantly increased than that in sham-operated rats. The total clearance (CLtot) and the biliary clearance (CLbile) in intestinal I/R rats reperfused 1 h were significantly decreased than those in sham-operated rats. Conclusions. Oatp1a1 and Oatp2b1 expression levels are decreased by intestinal I/R. The decreases in these transporters cause alteration of pharmacokinetics of organic anion compound. The newly found influence of intestinal I/R on the expression and function of Oatps may be a key to perform appropriate drug therapy.

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“…In addition, other factors that can down-regulate Oatp1a1 expression include hyperthyroidism (Engels et al, 2015), high-cholesterol diet (Kawase et al, 2017), caloric restriction (Kulkarni et al, 2013), dysbiosis (Kuno et al, 2016), rheumatoid arthritis (Lin et al, 2017), intestinal ischemia-reperfusion (Maruyama et al, 2013), diabetes (Shuboni-Mulligan et al, 2019), hepatic metastatic tumors (Sun et al, 2006), oxidative stress (Tsujimoto et al, 2013) and polycystic kidney disease (Bezençon et al, 2019). From the available reports, almost all pathological changes down-regulate Oatp1a1 expression.…”

Section: Oatp1a1 In Pathological Statementioning

confidence: 99%

The role of OATP1A1 in cholestasis and drug-induced toxicity: a systematic review

et al. 2022

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Organic anion transport protein 1a1 (Oatp1a1) is the prototypical member of the Oatp family of highly homologous transport proteins that are highly expressed in the liver and kidney (Cheng et al., 2005;Imai et al., 2013). In the liver, Oatp1a1 is expressed in all hepatocytes, and uniformly distributed on the basolateral (sinusoidal) surface of hepatocytes (Wang et al., 2008). Oatp1a1 expression is influenced by gender. Oatp1a1 expression in rat liver is predominantly male (Hou et al., 2014). In contrast, Oatp1a1 in kidney is predominantly female (Cheng et al., 2006). However, it is also believed that the expression of Oatp1a1 is higher in kidney of males than that of females (Cheng et al., 2005). The expression of Oatp1a1 tends to be up-regulated and then down-regulated with increasing age. Oatp1a1 is barely detectable in the liver of fetal rats, and its expression is low at birth, and increase rapidly after weaning, reaching a peak at 60 days. It then remains stable from 60 to 180 days of age, and

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Effect of oxidative stress on expression and function of human and rat organic anion transporting polypeptides in the liver

Abstract: 17Reactive oxygen species (ROS) have physiological function and involve alteration of 18 physical state. However, it is not clear effect of oxidative stress on pharmacokinetics. Organic

Cited by 9 publications

References 37 publications

Scutellarin inhibition of the rosuvastatin uptake in rat hepatocytes and the competition for organic anion transporting polypeptide 1B1 in HEK293T cells

Scutellarin inhibition of the rosuvastatin uptake in rat hepatocytes and the competition for organic anion transporting polypeptide 1B1 in HEK293T cells

Intestinal Ischemia-Reperfusion Suppresses Biliary Excretion of Hepatic Organic Anion Transporting Polypeptides Substrate

The role of OATP1A1 in cholestasis and drug-induced toxicity: a systematic review

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