Reversal of Stage-I Sugar Cataract by Sorbinil, an Aldose Reductase Inhibitor

Beyer‐Mears, A.; Cruz, E.; Varagiannis, E.

doi:10.1159/000138103

Cited by 20 publications

(12 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Twelve diabetic animals meeting the aforementioned criterion received sorbinil in a daily oral dose of 20 mg/kg body weight. For 4 months, food and aldose reductase inhibitor consumption were monitored daily by weighing food dishes and calculating the amount of sorbinil ingested, as previously described [6,9,10]. For comparison, 10 nondiabctic BB resis tant controls and 7 additional type 1 diabetic BB rats did not receive sorbinil treatment.…”

Section: Methodsmentioning

confidence: 99%

Reversal of Proteinuria by Sorbinil, an Aldose Reductase Inhibitor in Spontaneously Diabetic (BB) Rats

Beyer‐Mears

Murray²,

Val³

et al. 1988

Pharmacology

Self Cite

View full text Add to dashboard Cite

Sorbinil, an aldose reductase inhibitor, was examined as a therapeutic agent to arrest and/or reverse proteinuria in ‘type 1’ insulin-dependent BB rats having spontaneous diabetes mellitus. Prior to sorbinil treatment, diabetic rats exhibited hyperglycemia and increased urinary excretion of urobilinogen, glucose and protein. To assess proteinuria, 24-hour urine samples were analyzed for both total protein and individual components between 30,000 and 100,000 daltons. Daily oral administration of sorbinil (20 mg/kg body weight) was initiated and the aforementioned parameters reevaluated after 1, 2 and 4 months. Results indicated that after 1 month of sorbinil treatment, urobilinogen was normalized in all diabetic BB rats (n = 12), whereas urinary protein excretion was either diminished (67%) or remained constant (16 %), despite persistence of hyperglycemia and glycosuria. These therapeutic effects were sustained after 2 months of sorbinil treatment. After 4 months, protein excretion was normalized (6.56 ± 3.34 mg/24h), despite persistence of hyperglycemia and glycosuria (n = 12); in marked contrast, 6 untreated rats continued to exhibit proteinuria (17.76 ± 2.59 mg/day). Sorbinil diminished albumin and a series of urinary proteins between 30,000 and 100,000 daltons, suggesting that sorbinil may represent a therapeutic approach to manage diabetic nephropathy as indicated by diminution of proteinuria.

show abstract

Section: Methodsmentioning

confidence: 99%

Reversal of Proteinuria by Sorbinil, an Aldose Reductase Inhibitor in Spontaneously Diabetic (BB) Rats

Beyer‐Mears

Murray²,

Val³

et al. 1988

Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Then their lenses were examined with a Zeiss slit-lamp biomi croscope and camera system as previously described [4,12]. We have had considerable experience with sorbinil in cataract model systems [2][3][4][5]. In the present study, we employed the lens as an outside reference for the renal data.…”

Section: Methodsmentioning

confidence: 99%

Diminished Proteinuria in Diabetes mellitus by Sorbinil, an Aldose Reductase Inhibitor

Beyer‐Mears¹,

Cruz²,

Edelist³

et al. 1986

Pharmacology

Self Cite

View full text Add to dashboard Cite

Proteinuria was diminished by concomitant oral administration of sorbinil, an aldose reductase inhibitor to streptozotocin-induced diabetic rats. Animals were placed in one of three groups: control, diabetic, sorbinil-treated diabetic. For a period of 10 weeks, 24-hour urine samples were analyzed weekly for volume, glucose, ketone, total protein (Pesce-Strande) and individual protein components having molecular weights between 15,000 and 120,000 daltons. The latter were examined by polyacrylamide gel electrophoresis and quantitated by laser densitometric analysis. Results indicated that controls excreted albumin (68,000 daltons) and low-molecular weight proteins between 15,000 and 20,000 daltons. Throughout the 10-week period of diabetes, there was a 7- to 12-fold increase in total urinary protein excreted in 24 h. Diabetic-induced proteinuria primarily resulted from excretion of newly detected proteins having molecular weights of 30,000–100,000 daltons and an increase amount of albumin. Sorbinil treatment prevented approximately 70% of the increase in total protein excretion despite persistent hyperglycemia, glycosuria and ketonuria. Laser densitometric analysis indicated that the aldose reductase inhibitor decreased by 70% the excretion of newly detected proteins and albumin while maintaining the 15,000- to 20,000-dalton proteins. These results suggest that the polyol pathway is implicated in diabetic-induced proteinuria and inhibition of aldose reductase may represent a therapeutic approach for management of diabetic nephropathy.

show abstract

“…In our previous studies, the primary objec tive was to diminish lens polyol content by inhibition of aldose reductase; simulta neously, sorbinil increased lens Ml content [16][17][18]. The present objective was to deter mine whether MI supplementation would prevent and/or diminish cataractogenesis.…”

Section: Discussionmentioning

confidence: 93%

“…Each animal had access to the indi vidual diet and water ad libitum. Diet consumption by each rat was monitored daily as described pre viously [16,18], Galactose and MI employed in diet supplementation were purchased from Sigma.…”

Section: Methodsmentioning

confidence: 99%

“…MI, a cyclic hexanol, is an essen tial growth factor required for cell multipli cation [5,6], amino acid transport [7,8] and activity of Na-K-adenosine triphosphatase (ATPase) [9], MI serves as substrate for syn thesis of phosphatidylinositol (PI) [10]. In the lens, differentiation of epithelium into fiber cells is accompanied by increased syn thesis and decreased turnover of PI; there fore, PI may be an endogenous regulator of cell differentiation [11][12][13], In both models of sugar cataract, lens epithelial cells layer upon themselves and fail to elongate into fiber cells [14,15], In our previous cataract reversal studies, the aldose reductase inhibi tor, sorbinil, promoted restoration of lens MI content, transparency and fiber cell in tegrity; it is possible that MI supplementa tion may provide these protective effects [16][17][18],…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dietary Myo-Inositol Effect on Sugar Cataractogenesis

et al. 1989

Self Cite

View full text Add to dashboard Cite

The lens myo-inositol (MI) content is known to be depleted during initial cataractogenesis in both streptozocin (STZ)-induced diabetic and 50% galactose-maintained rats. The objective of this study is to establish whether dietary MI supplementation protects lens transparency, MI content and individual fiber cell ultrastructure in both model systems of sugar cataract. In the diabetic study, after induction with STZ, rats were immediately placed on normal chow supplemented with 2% MI for 14 weeks while additional age-matched control and diabetic rats remained untreated. Within 14 weeks, untreated diabetic rat lenses were totally opaque with undetectable MI content; MI was undetectable by 1 month. These opaque lenses were devoid of fiber cells and exhibited only acellular, amorphous cortical regions between 0 and 500 µm from the capsule. In contrast, 14-week, MI-treated diabetic rat lenses exhibited only cortical vacuolation indicative of initial cataractogenesis; MI content was 0.41 ± 0.26 µmol/g wet weight of lens. Scanning electron micrographs indicated a granulated, acellular region subadjacent to the capsule and confirmed the presence of cortical fiber cells, approximately 100 µm from the capsule. In 50% galactose-maintained rats, daily administration of MI for 1 month was unable to prevent total opacification or reverse initial cataractogenesis indicating that in rapidly progressing galactose cataracts, MI was unable to protect lens transparency, MI content and cortical fiber ultra-structure. The combined results suggest that MI may exert a protective effect on the slowly developing diabetic cataract. Of the 2 models, the time course and polyol content in STZ diabetic lenses more closely correlate to the human diabetic lens which has a low activity of aldose reductase; therefore, it is possible that MI may exert a protective effect in human diabetic cataract.

show abstract

Reversal of Stage-I Sugar Cataract by Sorbinil, an Aldose Reductase Inhibitor

Cited by 20 publications

References 14 publications

Reversal of Proteinuria by Sorbinil, an Aldose Reductase Inhibitor in Spontaneously Diabetic (BB) Rats

Reversal of Proteinuria by Sorbinil, an Aldose Reductase Inhibitor in Spontaneously Diabetic (BB) Rats

Diminished Proteinuria in Diabetes mellitus by Sorbinil, an Aldose Reductase Inhibitor

Dietary Myo-Inositol Effect on Sugar Cataractogenesis

Contact Info

Product

Resources

About