Effect of probucol in a murine model of slowly progressive polycystic kidney disease

Nagao, Shizuko; Yamaguchi, Tomohiro; Kasahara, Masao; Kusaka, Masaru; Matsuda, Jun; Ogiso, Noboru; Takahashi, Hisahide

doi:10.1016/s0272-6386(00)70330-1

Cited by 21 publications

(12 citation statements)

References 32 publications

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“…Because targeting a downstream step generally is more efficient and more specific, inhibition of the ERK pathway may provide a promising approach to the treatment of PKD. Notably, lovastatin and probucol, which have been reported to slow the progression of cystic growth, are known to inhibit ERK (37,38). Future studies are warranted to clarify the role of ERK in other animal models of PKD as well as to develop efficient therapeutic modalities for inhibition of ERK in humans.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Signal–Regulated Kinase Inhibition Slows Disease Progression in Mice with Polycystic Kidney Disease

Omori¹,

Hida²,

Fujita³

et al. 2006

Journal of the American Society of Nephrology

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131

104

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The expression of mitogen-activated protein kinases (MAPK) in DBA/2-pcy/pcy (pcy) mice, a murine model of polycystic kidney disease was investigated. Proliferating cell nuclear antigen-positive cells were recognized in cyst epithelium from embryonic day 14.5 to 25 wk of age. Extracellular signal-regulated kinase (ERK) was expressed in the renal tubules of control and pcy mice, but stronger immunostaining was observed in cyst epithelium. Phosphorylated ERK was detected only in pcy mice and was localized predominantly in the cysts. p38 MAPK (p38) was no longer expressed after birth in controls but was detected in the cyst epithelium and in occasional tubular cells of pcy mice at all stages examined. c-Jun N-terminal kinase (JNK) was expressed in all tubular segments of controls after neonatal day 7, whereas in pcy kidneys, tubules became positive for JNK after 8 wk, and the cysts expressed little JNK. Administration of an oral MAP/ERK kinase inhibitor, PD184352, 400 mg/kg per d, to 10-wk-old pcy mice daily for the first week and then every third day for 6 additional weeks significantly decreased BP, kidney weight, serum creatinine level, and water intake and significantly increased urine osmolality. The cystic index and expression of phosphorylated ERK and ERK were significantly lower in PD184352-treated pcy mice. These results demonstrate that the expression of MAPK is dysregulated in cyst epithelium and that inhibition of ERK slowed the progression of renal disease in pcy mice.

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Section: Discussionmentioning

confidence: 99%

Extracellular Signal–Regulated Kinase Inhibition Slows Disease Progression in Mice with Polycystic Kidney Disease

Omori¹,

Hida²,

Fujita³

et al. 2006

Journal of the American Society of Nephrology

Self Cite

131

104

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“…[15][16][17][18][19][20] In addition, studies have reported that the antioxidant vitamin E and the antihypercholesterolemic agent probucol reduce nephrotoxicity. 21,22) However, few drugs with antioxidant activity are clinically available, and such drugs are not used for antioxidant purposes. In this study, we investigated the physiological action and mechanism of action of ESE on ADR nephropathy, which was considered to be strongly influenced by oxidant stress.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Eriobotrya japonica Seed Extract on Oxidative Stress in Adriamycin-Induced Nephropathy in Rats

Hamada

Yoshioka

Takuma

et al. 2004

Biological & Pharmaceutical Bulletin

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Recent studies have shown that oxidative damage in the body induced by reactive oxygen species (ROS) and free radicals is frequently involved in the development of many diseases.1-3) ROS are continuously produced physiologically, and play an important role in the expression of cell functions such as the transmission of impulse information. However, if they are produced excessively from any cause, they act cytotoxically as mediators of adverse events such as inflammation, necrosis, and apoptosis. In the kidney, ROS are important causes of acute and subacute renal failure in most cases. It has also been reported that renal failure results from decreased levels of the antioxidant vitamin E and decreased activity of the antioxidant enzyme glutathione peroxidase (GPx), 4,5) and can be prevented by free-radical scavengers and polyphenols. 6,7) Also, certain anticancer drugs themselves produce free radicals, and act as factors promoting nephrotoxicity. 8) In particular, adriamycin (ADR), which is used to treat leukemia and lung cancer, generates superoxide anions and hydroxy radicals, thereby inducing nephrotoxicity, suggesting that the administration of antioxidant substances is effective in inhibiting nephrotoxicity. However, no clinically useful drugs are currently available.Eriobotrya japonica is widely cultivated as a fruit crop. Among Chinese medicine preparations, Eriobotrya japonica folia are an ingredient in Shini-seihai-to and Biwayo-to used as antiphlogistic, analgesic, antitussive, and expectorant agents. Recently, the blood sugar-reducing 9-11) and antiphlogistic actions 12,13) of Eriobotrya japonica folia have also been reported. On the other hand, Eriobotrya japonica seeds, like those of apricots and peaches of the same genus (Rosaceae), contain amygdalin as the main constituent; therefore, they were used as a substitute medication for the latter seeds in prewar Japan.To date, we have discovered the antioxidant action and associated hepatotoxicity-inhibiting action of an extract from Eriobotrya japonica seeds.14) In this study, to clarify the physiological action of an extract from Eriobotrya japonica seeds, we administered an Eriobotrya japonica seed extract (ESE) with 70% ethanol to rats with ADR nephrotoxicity, and evaluated its improvement effect. MATERIALS AND METHODS MaterialsSufficiently sun-dried seeds of Mogi-loquant collected at Muroto and Susaki cities in Kochi Prefecture of Japan were the Eriobotrya japonica seeds used. Adriamycin (ADR) was provided by Kyowahakko (Japan). All other chemicals were of reagent grade.Extraction of Seed Eriobotrya japonica seeds were extracted by 70% ethanol. Briefly, 1.0 kg of seeds was crushed in a blender equipped with a refrigerator at 1000 rpm, and then continuously stirred by a mixer at 300 rpm for 7 d after being dissolved in the 70% ethanol. The supernatant was then collected and evaporated to dryness to prepare the dried extracts.Animals Male Wistar rats, aged seven weeks, 180-200 g, were purchased from NSC Japan. Animals were acclimatized for seven days ...

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“…It protects against renal scaring in diabetic nephropathy [67], focal segmental glomerulosclerosis (FSGS) [68], obstructive nephropathy [69], polycystic kidney disorder [70] and remnant kidney [71]. The favorable renal effects of probucol in membranous nephropathy were demonstrated both in an experimental model and in a clinical study [72,73].…”

Section: Lipid-lowering Agentsmentioning

confidence: 99%

Antioxidants: A Possible Role in Kidney Protection

Tylicki

Rutkowski

Hörl

2003

Kidney Blood Press Res

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Oxidative stress contributes to the pathophysiology of kidney injury. Beneficial renal effects of some medications, such as angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor antagonists, calcium channel blockers, β-blockers and lipid lowering agents depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in prevention and attenuation of renal scaring in numerous animal models of kidney diseases. These include vitamins, N-acetylcysteine, α-lipoic acid, melatonin, dietary flavonoids and phytoestrogens, and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen renal damage. To date, the evidence is insufficient to recommend antioxidant supplements in patients with kidney disease. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies are indispensable.

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Effect of probucol in a murine model of slowly progressive polycystic kidney disease

Cited by 21 publications

References 32 publications

Extracellular Signal–Regulated Kinase Inhibition Slows Disease Progression in Mice with Polycystic Kidney Disease

Extracellular Signal–Regulated Kinase Inhibition Slows Disease Progression in Mice with Polycystic Kidney Disease

The Effect of Eriobotrya japonica Seed Extract on Oxidative Stress in Adriamycin-Induced Nephropathy in Rats

Antioxidants: A Possible Role in Kidney Protection

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