Differential effects of nephrotoxic agents on renal transport and metabolism by use of in vitro techniques.

Hirsch, G. H.

doi:10.1289/ehp.761589

Cited by 44 publications

(12 citation statements)

References 25 publications

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“…The PAH uptake was significantly increased by 30 or 60 min o f ischemia in the rabbit, in agree ment with data reported in rats [14,15]. Since similar obser vations have been demonstrated in drug-induced nephrotox icity [29][30][31], it seems unlikely that stimulation of the PAH transport is a specific response to renal ischemia. Similarly, 30 or 60 min of ischemia significantly stimulated the slice uptake of the organic cation TEA in a manner comparable to the effect on PAH uptake.…”

Section: Changes In Organic Ion Transport In Cortical Slicessupporting

confidence: 89%

Effect of Renal Ischemia on Organic Anion and Cation Transport in Rabbit Proximal Tubule

Kim

Kim²,

Jung³

et al. 1996

Kidney Blood Press Res

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The uptake of organic anion, ρ-aminohippurate (PAH), and organic cation, tetraethylammonium (TEA), was measured in cortical slices and plasma membrane vesicles isolated from the proximal tubule of ischemic rabbit kidneys. The uptake of PAH or TEA in cortical slices increased after 30 or 60 min of ischemia. When the kidneys were reperfused for 30 min, the uptake of organic ions returned to control levels. When ischemic (60 min) slices were preincubated for 120 min in an oxygenated medium, the stimulatory effect of ischemia on organic ion uptake was not observed. The PAH uptake by basolateral membrane vesicles and brush border membrane vesicles (BBMV) was not altered following 60 min of ischemia. However, the TEA uptake by BBMV but not basolateral membrane vesicles was significantly reduced. The dissipation rate of H⁺ gradient across the BBMV was similar in control and ischemic kidneys. The V_max for TEA transport in BBMV isolated from ischemic kidneys was significantly reduced, but the K_mwas not altered. These results indicate that the organic cation secretory system is more vulnerable to ischemia than the organic anion secretory system in the rabbit renal proximal tubule.

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Section: Changes In Organic Ion Transport In Cortical Slicessupporting

confidence: 89%

Effect of Renal Ischemia on Organic Anion and Cation Transport in Rabbit Proximal Tubule

Kim

Kim²,

Jung³

et al. 1996

Kidney Blood Press Res

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“…Renal cortical accumulation of organic ions has been used as a sensitive indicator in the assessment of nephrotoxicity [21]. We, therefore, measured in the present study the uptake of organic anion PAH by renal cortical slices as a biochemical index for an in vitro evaluation of proximal tubular cell injury.…”

Section: Resultsmentioning

confidence: 99%

Salviae Radix Extract Prevents Cisplatin-Induced Acute Renal Failure in Rabbits

Jeong

W²,

Yoon³

et al. 2001

Nephron

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The present study was carried out to determine if salviae radix extract (SRE) exerts a beneficial effect against cisplatin-induced renal failure in rabbits. Rabbits were pretreated with SRE orally for 7 days, followed by cisplatin injection (5 mg/kg i.p.). Cisplatin injection caused a reduction in GFR, which was accompanied by an increase in serum creatinine levels. The fractional Na⁺ excretion was increased by cisplatin injection. PAH uptake by renal cortical slices was inhibited by the administration of cisplatin. Such changes were prevented by SRE pretreatment. Cisplatin injection increased lipid peroxidation, which was prevented by SRE pretreatment. The protective effect of SRE was supported by morphological studies. Cisplatin injection reduced renal blood flow that was not affected by SRE pretreatment. Cisplatin treatment in vitro in renal cortical slices increased LDH release and lipid peroxidation, which were prevented by 0.05% SRE. These results indicate that lipid peroxidation plays a critical role in cisplatin-induced acute renal failure. SRE exerts a protective effect against renal cell injury induced by cisplatin, and its effect may be attributed to its antioxidant action. However, the underlying mechanism by which SRE has antioxidant action remains to be defined.

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“…PAH accumulation in the slices was expressed as the ratio of the level of PAH in slices (S) to medium (M). Accumulation of PAH in renal cortical slices was used as an index of renal cell injury (Hirsch, 1976;Cojocel et al, 1983).…”

Section: Determination Of Pah Accumulationmentioning

confidence: 99%

Involvement of Raf-1/Mek/Erk1/2 Signaling Pathway in Zinc-Induced Injury in Rat Renal Cortical Slices

et al. 2006

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-Zinc is an essential nutrient that can also be toxic. We have previously reported that zincrelated renal toxicity is due, in part, to free radical generation in the renal epithelial cell line, LLC-PK 1 cells. We have also shown that an MEK1/2 inhibitor, U0126, markedly inhibits zinc-induced renal cell injury. In this study, we investigated the role of an upstream MEK/ERK pathway, Raf-1 kinase pathway, and the transcription factor and ERK substrate Elk-1, in rat renal cortical slices exposed to zinc. Immediately after preparing slices from rat renal cortex, the slices were incubated in medium containing Raf-1 and MEK inhibitors. ERK1/2 and Elk-1 activation were determined by Western blot analysis for phosphorylated ERK (pERK) 1/2 and phosphorylated Elk-1 (pElk-1) in nuclear fractions prepared from slices exposed to zinc. Zinc caused not only increases in 4-hydroxynonenal (4-HNE) modified protein and lipid peroxidation, as an index of oxidant stress, and decreases in PAH accumulation, as that of renal cell injury in the slices. Zinc also induced a rapid increase in ERK/Elk-1 activity accompanied by increased expressions of pERK and pElk-1 in the nuclear fraction. A Raf-1 kinase inhibitor and an MEK1/2 inhibitor U0126 significantly attenuated zinc-induced decreases PAH accumulation in the slices. The Raf-1 kinase inhibitor and U0126 also suppressed ERK1/2 activation in nuclear fractions prepared from slices treated with zinc. The present results suggest that a Raf-1/MEK/ERK1/2 pathway and the ERK substrate Elk-1 are involved in free radical-induced injury in rat renal cortical slices exposed to zinc.

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Differential effects of nephrotoxic agents on renal transport and metabolism by use of in vitro techniques.

Cited by 44 publications

References 25 publications

Effect of Renal Ischemia on Organic Anion and Cation Transport in Rabbit Proximal Tubule

Effect of Renal Ischemia on Organic Anion and Cation Transport in Rabbit Proximal Tubule

Salviae Radix Extract Prevents Cisplatin-Induced Acute Renal Failure in Rabbits

Involvement of Raf-1/Mek/Erk1/2 Signaling Pathway in Zinc-Induced Injury in Rat Renal Cortical Slices

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