Pharmacokinetics and tissue distribution of uraemic indoxyl sulphate in rats

Deguchi, Toshio; Nakamura, Mikio; Tsutsumi, Yasuhiro; Suenaga, Atsushi; Otagiri, Masaki

doi:10.1002/bdd.370

Cited by 27 publications

(22 citation statements)

References 24 publications

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“…Experimental CRF was induced by 5/6 Nx (Deguchi et al, 2003). Male Wistar rats (130 -150 g) were anesthetized with sodium pentobarbital (60 mg/kg) by intraperitoneal injection.…”

Section: Methodsmentioning

confidence: 99%

“…Under light anesthesia with 60 mg/kg phenobarbital, normal Wistar rats (250 -290 g) and 5/6 Nx rats underwent a surgical procedure in which cannulas were inserted into the femoral vein and artery using polyethylene tubing (polyethylene-50; i.d., 0.58 mm; o.d., 0.9655 mm; BD Biosciences, Parsippany, NJ) (Deguchi et al, 2003 )] as a rapid infusion into the femoral vein. GFR was assumed to be equal to the renal clearance of inulin.…”

Section: Methodsmentioning

confidence: 99%

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Renal Clearance of Endogenous Hippurate Correlates with Expression Levels of Renal Organic Anion Transporters in Uremic Rats

Deguchi

Takemoto²,

Uehara³

et al. 2005

J Pharmacol Exp Ther

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Hippurate (HA) is a harmful uremic toxin that accumulates during chronic renal failure, and failure of the excretion system for uremic toxins is thought to be responsible. Recently, we reported that rat organic anion transporter 1 (rOat1) is the primary mediator of HA uptake in the kidney, and so now we have studied the pharmacokinetics and tissue distribution of HA after a single i.v. dose of HA to normal and 5/6 nephrectomized rats (5/6Nx rats). In control rats, the renal and biliary clearances of HA were 18.1 and 0.1 ml/min/kg, respectively. Plasma clearance decreased as dosage increased from 0.1 to 5 mg/kg, which suggests that renal tubular secretion is the primary route for elimination of HA. The plasma clearance of HA was significantly decreased in 5/6 Nx rats compared with normal rats. In 5/6 Nx rats, renal clearance of endogenous HA correlated more closely with clearance of p-aminohippurate than with that of creatinine. Protein expression of rOat1 and rOat3, assessed by Western blot analysis, was decreased in 5/6 Nx rats. Furthermore, in 5/6 Nx rats, the renal secretory clearance of endogenous HA correlated closely with protein expression of renal rOats. Thus, HA is primarily eliminated from the plasma via the kidney by active tubular secretion. The renal clearance of endogenous HA seems to be a useful indicator of changes in renal secretion that accompany the reduced levels of OAT protein in chronic renal failure.

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“…Experimental CRF was induced by 5/6 Nx (Deguchi et al, 2003). Male Wistar rats (130 -150 g) were anesthetized with sodium pentobarbital (60 mg/kg) by intraperitoneal injection.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Renal Clearance of Endogenous Hippurate Correlates with Expression Levels of Renal Organic Anion Transporters in Uremic Rats

Deguchi

Takemoto²,

Uehara³

et al. 2005

J Pharmacol Exp Ther

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“…The serum level of IS is known to be markedly elevated in the serum of patients with CKD (the serum concentration 100 :M-1 mM in the case of CKD 12,18,[19][20][21]22,24,24,25,[26][27][28] Albumin Binding (Binding Site) 29 patients versus 0.1-10 :M in healthy subjects), 65,66 and recent clinical studies have shown that IS plays a role in the progression of CKD. [3][4][5] In the intestinal tract, bacteria such as Escherichia coli express tryptophanase, which catalyzes the formation of indole from dietary tryptophan.…”

Section: Indoxyl Sulfatementioning

confidence: 99%

Update on the Pharmacokinetics and Redox Properties of Protein-Bound Uremic Toxins

Watanabe

Miyamoto

Otagiri

et al. 2011

Journal of Pharmaceutical Sciences

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“…Fiveweek-old male rats weighing 140-150 g were subjected to a 5/6 nephrectomy, as previously described. 7,8) Six weeks after the operation, the treated rats showed increased plasma concentrations of creatinine (Ͼ1.0 mg/dl), and reduced levels of creatinine clearance (1.12 approximately 1.24 ml/min). Agematched Sham-operated rats were used for comparison.…”

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confidence: 99%

Evaluation for Antioxidant and Renoprotective Activity of Olmesartan Using Nephrectomy Rats

Kadowaki

Anraku

Tasaki

et al. 2009

Biological & Pharmaceutical Bulletin

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The renin-angiotensin system (RAS) plays an important role in regulating blood pressure (BP). It has recently been revealed that the elevated levels of RAS are associated with various organ impairments. Thus, an angiotensin II receptor blocker (ARB) and an angiotensin converting enzyme inhibitor (ACEI) are effective for treating hypertension and show protective effects for the heart or kidney. For example, in a clinical trial in which the effect of ARB valsartan and calcium channel blocker (CCB) amlodipine were compared in patients with diabetes, valsartan was found to decrease the urinary albumin excretion rate to a greater extent than CCB, while BP was reduced to the same level.1) Consequently, RAS antagonists may exert a renal protective effect that is independent of its antihypertensive effect, and may be involved in reducing of the levels of oxidative stress. In fact, contrary to CCB, ARB improved endothelium-dependent coronary dilation in hypertensive patients independent of BP reduction. These beneficial effects on coronary vasomotion might be a result of the antioxidant properties of ARBs. 2)Olmesartan medoxomil, a prodrug that is converted into the active metabolite olmesartan has recently been developed in association with ARB.3,4) Miyata et al. reported that the antioxidant effects of olmesartan were greater than any other ARBs in an in vitro study. 5) We recently reported, in an in vitro study, that clinical concentrations of olmesartan exert antioxidant properties. This was further confirmed in a clinical trial for hemodialysis (HD) patients as well.6) We also reported that the antioxidant effects of olmesartan might be independent of its BP lowering ability. To develop a better understanding of the antioxidant effect of olmesartan in vivo, relationships between the antioxidant activity of olmesartan and pharmacological effects, such as renoprotective or BP lowering effects, were examined using the 5/6 nephrectomy rat. MATERIALS AND METHODS MaterialsOlmesartan was obtained from the DaiichiSankyo Pharmaceutical Co., Ltd. (Tokyo, Japan). All other chemicals were of the highest grade available from commercial sources.Animals and Treatment Male Wister rats were purchased from Seac Yoshitomi, Ltd. (Fukuoka, Japan). The experimental protocol was inspected and approved by the Animal Care and Use Committee of School of Medicine, Kumamoto University and the law and notification of the Japanese government prior to commencement of the study. Fiveweek-old male rats weighing 140-150 g were subjected to a 5/6 nephrectomy, as previously described. 7,8) Six weeks after the operation, the treated rats showed increased plasma concentrations of creatinine (Ͼ1.0 mg/dl), and reduced levels of creatinine clearance (1.12 approximately 1.24 ml/min). Agematched Sham-operated rats were used for comparison. These rats were divided into three groups as follows: (a) untreated nephrectomized group (nϭ4-6). (b) Olmesartan (10 mg/kg/d) treated nephrectomized group (nϭ4-6). (c) Sham-operated rats (nϭ4-6). All of the rats received s...

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Pharmacokinetics and tissue distribution of uraemic indoxyl sulphate in rats

Cited by 27 publications

References 24 publications

Renal Clearance of Endogenous Hippurate Correlates with Expression Levels of Renal Organic Anion Transporters in Uremic Rats

Renal Clearance of Endogenous Hippurate Correlates with Expression Levels of Renal Organic Anion Transporters in Uremic Rats

Update on the Pharmacokinetics and Redox Properties of Protein-Bound Uremic Toxins

Evaluation for Antioxidant and Renoprotective Activity of Olmesartan Using Nephrectomy Rats

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