Morphometric changes in the duodenal microvillous surface area of the non-pregnant, pregnant and lactating female rat

In the present study an attempt has been made to describe the morphometrical changes occurring in the microvilli of the duodenum of rats of different ages and periods of reproduction. The data showed that the microvillous surface area in the duodenum was greatest in senescent rats and lowest in adult and old animals. The values for lactating rats were similar to that for the senescent group. There was a direct correlation between the microvillous surface area with the height and density. By contrast, however, there was a negative correlation between the width and density of the duodenal microvilli.     

Is sorbital dehydrogenase gene expression affected by streptozotocin-diabetes in the rat?

The polyol pathway, which comprises the enzymes aldose reductase and sorbitol dehydrogenase, is recognised to play a major role in the pathogenesis of diabetic complications. Although there has been extensive research on aldose reductase, the role of sorbitol dehydrogenase has been overlooked. This study examined the response of sorbitol dehydrogenase gene expression to streptozotocin-diabetes (STZ-diabetes) in the rat and whether these changes were reversed by insulin. STZ-diabetes increased testicular sorbitol dehydrogenase gene expression in a manner that was not reversible by insulin but had no effect on gene expression in kidney and brain. A secondary question was the relationship between sorbitol dehydrogenase and aldose reductase gene expression in STZ-diabetes. STZ-diabetes increased renal dose reductase gene expression in a manner that was not reversible by insulin but had no effect on gene expression in the brain, testes and muscle. Thus, STZ-diabetes causes changes in sorbitol dehydrogenase gene expression which do not parallel those in aldose reductase, implying that expression of the two genes is not regulated via a common mechanism. Furthermore, changes in sorbitol dehydrogenase and aldose reductase gene expression cannot be fully explained on the basis of the osmoregulatory hypothesis, suggesting that regulation is mediated via mechanisms that are multifactorial and tissue-specific.     

Inhibitory effects of astragaloside IV on diabetic peripheral neuropathy in rats

Astragaloside IV (AGS-IV), a new glycoside of cycloartane-type triterpene isolated from the root of Astragalus membranaceus (Fisch.) Bunge, has been used experimentally for its potent immune-stimulating, anti-inflammatory, and antioxidative actions. A recent study has shown AGS-IV to be an aldose-reductase inhibitor and a free-radical scavenger. This study examined the effects of AGS-IV on motor nerve conduction velocity (MNCV), tailflick threshold temperature, biochemical indexes, and the histology of the sural nerve after diabetes was induced in rats with 75 mg/kg streptozotocin (STZ). AGS-IV (3, 6, 12 mg/kg, twice a day) was administered by oral gavage for 12 weeks after diabetes was induced. Compared with control (nondiabetic) rats, obvious changes in physiological behaviors and a significant reduction in sciatic MNCV in diabetic rats were observed after 12 weeks of STZ administration. Morphological analysis showed that AGS-IV suppressed a decrease in myelinated fiber area, an increase in myelinated fiber density, and an increase in segmental demyelination in diabetic rats. The protective mechanism of AGS-IV involved a decrease in declining blood glucose concentration and HbA1C levels, and an increase in plasma insulin levels. AGS-IV increased the activity of glutathione peroxidase in nerves, depressed the activation of aldose reductase in erythrocytes, and decreased the accumulation of advanced glycation end products in both nerves and erythrocytes. Moreover, AGS-IV elevated Na+,K+-ATPase activity in both the nerves and erythrocytes of diabetic rats. These results indicate that AGS-IV exerts protective effects against the progression of peripheral neuropathy in STZ-induced diabetes in rats through several interrelated mechanisms.     

Deficient renal 20-HETE release in the diabetic rat is not the result of oxidative stress

We confirmed that release of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated perfused kidney of diabetic rats is greatly reduced compared with age-matched control rats. The present studies were undertaken to examine potential mechanisms for the deficit in renal 20-HETE in rats with streptozotocin-induced diabetes of 3-4 wk duration. A role for oxidative stress was excluded, inasmuch as treatment of diabetic rats with tempol, an SOD mimetic, for 4 wk did not affect the renal release of 20-HETE. Similarly, chronic inhibition of nitric oxide formation with nitro-l-arginine methyl ester or aldose reductase with zopolrestat failed to alter the release of 20-HETE from the diabetic rat kidney. Inasmuch as 20-HETE may be metabolized by cyclooxygenase (COX), the expression/activity of which is increased in diabetes, we included indomethacin in the perfusate of the isolated kidney to inhibit COX but found no effect on 20-HETE release. Diabetic rats were treated for 3 wk with fenofibrate to increase expression of cytochrome P-450 (CYP4A) in an attempt to find an intervention that would restore release of 20-HETE from the diabetic rat kidney. However, fenofibrate reduced 20-HETE release in diabetic and control rat kidneys but increased expression of CYP4A. Only insulin treatment of diabetic rats for 2 wk to reverse the hyperglycemia and maintain blood glucose levels at <200 mg/dl reversed the renal deficit in 20-HETE. We conclude that oxidative stress, increased aldose reductase activity, or increased COX activity does not contribute to the renal deficit of 20-HETE in diabetes, which may be directly related to insulin deficiency.     

Adenosine triphosphatase activity in sciatic nerve tissue of streptozocin-induced diabetic rats with and without high dietary sucrose: effect of aldose reductase inhibitors.

The ability of aldose reductase inhibitors to prevent the decline in neural Na+,K(+)-ATPase activity in diabetic rats has not been confirmed by all laboratories. In this study, the efficacy of two structurally different aldose reductase inhibitors was evaluated under different experimental conditions. Na+,K(+)-ATPase activity was measured in sciatic nerves from streptozocin-induced diabetic rats fed normal rodent chow or a chow supplemented with 68% sucrose. Nerve homogenates from chow-fed rats were prepared with a Dounce tissue grinder, whereas homogenates from the sucrose-fed rats were prepared with an Ultra-Turrax disperser. In the chow-fed rats, 4 weeks of untreated diabetes resulted in an increase in neural sorbitol and fructose, a decrease in myoinositol, and a 54% decline in Na+,K(+)-ATPase activity. Sorbinil administration (20 mg/kg/day) completely prevented the rise in sorbitol and fructose and the depletion of myoinositol, but did not prevent the decline in Na+,K(+)-ATPase activity. In diabetic rats fed the sucrose diet for 4, 6, and 8 weeks, the neural sorbitol and fructose levels were elevated, the myoinositol concentration declined, and the Na+,K(+)-ATPase activity was 26 to 28% below the control. Prevention or intervention treatment with sorbinil (20 mg/kg/day) or tolrestat (50 mg/kg/day) for 4 to 6 weeks prevented the alterations in sorbitol, fructose, and myoinositol, and also prevented the decline in Na+,K(+)-ATPase activity. In conclusion, prevention and intervention therapy with aldose reductase inhibitors prevented the decline in Na+,K(+)-ATPase in sciatic nerves of sucrose-fed streptozocin-diabetic rats that were homogenized with an Ultra-Turrax disperser, but not in sciatic nerves from streptozocin-diabetic rats fed normal rodent chow that were homogenized with a Dounce tissue grinder. These findings indicate that the assessment of aldose reductase inhibitor efficacy is dramatically affected by the type of nerve preparation assayed and/or the diet.     

Beneficial influence of fungal metabolite nigerloxin on eye lens abnormalities in experimental diabetes

Osmotic and oxidative stress have been implicated in the pathogenesis of diabetic cataract. Nigerloxin, a fungal metabolite, has been shown to possess aldose reductase inhibitory and free radical scavenging potential, in vitro. In the present study, the beneficial influence of nigerloxin was investigated on diabetes-induced alteration in the eye lens of rats treated with streptozotocin. Groups of diabetic rats were administered nigerloxin orally (100?mg·(kg body mass)(-1)·day(-1)) for 30?days. The activity of lens polyol pathway enzymes?(aldose reductase and sorbitol dehydrogenase), lipid peroxides, and advanced glycation end products (AGEs) were increased in the diabetic animals. Levels of glutathione as well as the activity of antioxidant enzymes?(superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase) were decreased in the eye lens of the diabetic animals. The administration of nigerloxin significantly decreased levels of lipid peroxides and AGEs in the lens of the diabetic rats. Increase in the activity of aldose reductase and sorbitol dehydrogenase in the lens was countered by nigerloxin treatment. The activity of glutathione and antioxidant enzyme in the lens was significantly elevated in nigerloxin-treated diabetic rats. Examination of the treated rats' eyes indicated that nigerloxin delayed cataractogenesis in the diabetic rats. The results suggest the beneficial countering of polyol pathway enzymes and potentiation of the antioxidant defense system by nigerloxin in diabetic animals, implicating its potential in ameliorating cataracts in diabetics.     

Effect of vanadate administration on polyol pathway in diabetic rat kidney.

Effect of oral administration of sodium orthovanadate for three weeks on polyol pathway in renal cortex and medulla was studied in control and alloxan diabetic rats. An enhancement in aldose reductase in cortex and medulla and sorbitol dehydrogenase in cortex was observed in alloxan diabetic rats. Despite depressed insulin secretion, vanadate treatment to diabetic rats counteracted hyperglycemia, normalized elevated enzyme activities and glucose level, prevented medullary sorbitol accumulation and markedly checked increase in kidney weight. These results show that vanadate causes marked improvement in renal hypertrophy and has an antidiabetogenic effect on polyol pathway in diabetic kidney.     

Partial reversal by rutin and quercetin of impaired cardiac function in streptozotocin-induced diabetic rats

The present investigation was carried out to evaluate the effects of the cyclodextrin complexes quercetin and rutin on left ventricle dysfunction in streptozotocin-induced diabetic rats. Diabetes was induced by streptozotocin (45 mg/kg body mass, i.v.) in Sprague-Dawley rats. Echocardiography and biochemical and histological studies were carried out under normal control, diabetic untreated, normal and diabetic vehicle (beta-cyclodextrin, p.o.), quercetin- (100 and 300 mg/kg, p.o.), and rutin- (100 and 300 mg/kg, p.o.) treated normal and diabetic animals at varying time intervals (1 and 12 weeks). The increase in the serum triglycerides and cholesterol levels was attenuated in the cyclo dextrin complexes of rutin-treated animals significantly more than in the quercetin-treated and diabetic vehicle-treated animals. Left ventricular diastolic dysfunction was observed in diabetic vehicle-treated animals after 12 weeks of the study as determined by a significant decrease in E-wave (45.91%), an increase in the A-wave (75.55%), and a decrease in the E/A ratio (70.14%). However, the percent decrease (after 12 weeks) in the E-wave, increase in the A-wave, and decrease in the E/A ratio were less in the cyclodextrin complexes of rutin-treated animals (100 and 300 mg/kg), which had the following values: E-wave, 12.22% and 13.80%; A-wave, 25.90% and 10.40%; and E/A ratio, 31.01% and 20.52%. In the quercetin-treated animals (100 and 300 mg/kg), which had the following values: E-wave, 40.44% and 36.44%; A-wave, 52.98% and 29.28%; and E/A ratio, 61.70% and 51.11%. Histopathological studies revealed that the degree of myocardial necrosis was less in rutin-treated animals compared with quercetin and diabetic vehicle-treated animals: rutin < quercetin < beta-cyclodextrin. Myocardial fructose levels were significantly increased in the diabetic vehicle-treated animals after 12 weeks of the study, suggesting an increment in the myocardial polyol pathway activity. However, myocardial fructose levels were significantly decreased in the rutin- and quercetin-treated animals compared with the vehicle-treated animals, possibly owing to their aldose reductase inhibitory activity. Quercetin and rutin treatment did not influence the echocardiographical and histo logical parameters in normal animals. Results from the present investigation demonstrated that rutin has a cardioprotective activity, and we conclude that the observed cardioprotection with rutin may be due to its aldose reductase inhibitory activity, as the enhanced aldose reductase pathway is implicated in the development of left ventricle dysfunction by several studies.     

Resistance of the diabetic rat nerve to ischemic inactivation

The resistance of the action potential to ischemic inactivation observed in diabetic patients has been reproduced in vivo in rat rendered diabetic with streptozotocin and, acutely, in normal rats given p.o. a load of glucose. The resistance phenomenon was not detected in galactosemic rats. The preservation of the action potential was reversed by the administration of insulin, but not by treatment with an aldose reductase (AR) inhibitor. The ischemic resistance is attributed to the metabolic availability of excess glucose to the nerve. AR does not appear to be involved in the phenomenon.     

The effect of diabetes on phosphatidylinositol turnover and calcium influx in myocardium

Diabetes was induced in rats by administration of streptozotocin. Diabetes occurred within 24 h after treatment. Two forms of diabetes were studied, an acute form (4 days) and a chronic form (2 months). In a separate experiment the effect of insulin and an aldose reductase inhibitor on acute diabetes was studied. Phosphoinositide labelling was done in biopsies of heart with [3H] myo-inositol. It was shown that the incorporation of myo-inositol amounted to about 65% in acute diabetes and 80% in chronic diabetes compared to age-matched controls. The incorporation both in atria and ventricles was affected in a similar way. Muscarinic receptor-mediated phosphatidylinositol breakdown and release of myo-Ins-1 P (myo-inositol 1-phosphate) was unaffected in diabetic hearts in the chronic model. In hearts of diabetic ketotic animals uncoupling of the muscarinic receptor from the phosphoinositide metabolism was apparent. Calcium net influx was significantly reduced in both acute and chronic diabetes compared to age-matched controls. Insulin supplementation to acute diabetic animals significantly improved phosphoinositide labelling with [3H] myo-inositol. No improvement was seen in calcium transport. An aldose reductase inhibitor also facilitated phosphoinositide labelling without improving calcium transport. It is suggested that phosphoinositide metabolism and calcium entry through the slow inward current are independent of one another and the former is sensitive to insulin. It is suggested that insulin by regulating the pool of phosphoinositides and release of endogenous calcium may modulate cardiac function.     

Effect of diabetes and Sorbinil treatment on phospholipid metabolism in rat glomeruli

To explore the hypothesis that changes in membrane phospholipids accompany tissue myo-inositol depletion and reduced (Na+ + K+)-ATPase activity in diabetes, we examined phospholipid concentrations in glomeruli isolated from control and streptozotocin-diabetic rats and the effect of diabetes on myo-[3H]inositol incorporation in vitro into glomerular phosphatidylinositol. Since the aldose reductase inhibitor, Sorbinil, prevents the fall in myo-inositol and the decrease in (Na+ + K+)-ATPase activity associated with diabetes, phospholipid and phosphatidylinositol content were also examined in glomeruli isolated from Sorbinil-treated diabetic rats. Total phospholipids (microgram phosphorus/mg dry weight) did not differ in the three groups of animals. The concentration of phosphatidylcholine was elevated in preparations from diabetic rats, both untreated and Sorbinil-treated. Phosphatidylethanolamine was reduced in glomeruli from Sorbinil-treated rats. Neither acute experimental diabetes nor Sorbinil treatment produced detectable changes in the glomerular concentration of phosphatidylinositol. In vitro incubations with glomeruli isolated from control and diabetic animals resulted in increased levels of incorporation of myo-[3H]inositol into phospholipids of diabetic glomeruli. The specific activity of [3H]phosphatidylinositol in glomeruli from diabetic rats was significantly greater than that in control samples. The findings do not support the postulate invoking correspondent changes in myo-inositol and phosphatidylinositol contents as contributory to diminished glomerular (Na+ + K+)-ATPase activity in diabetes, but are compatible with depletion of glomerular intracellular myo-inositol in diabetes.     

Efficacy of lower doses of vanadium in restoring altered glucose metabolism and antioxidant status in diabetic rat lenses

Vanadium compounds are potent in controlling elevated blood glucose levels in experimentally induced diabetes. However the toxicity associated with vanadium limits its role as therapeutic agent for diabetic treatment. A vanadium compound sodium orthovanadate (SOV) was given to alloxan-induced diabetic Wistar rats in lower doses in combination withTrigonella foenum graecum, a well-known hypoglycemic agent used in traditional Indian medicines. The effect of this combination was studied on lens morphology and glucose metabolism in diabetic rats. Lens, an insulin-independent tissue, was found severely affected in diabetes showing visual signs of cataract. Alterations in the activities of glucose metabolizing enzymes (hexokinase, aldose reductase, sorbitol dehydrogenase, glucose-6-phosphate dehydrogenase) and antioxidant enzymes (glutathione peroxidase, glutathione reductase) besides the levels of related metabolites, [sorbitol, fructose, glucose, thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH)]were observed in the lenses from diabetic rats and diabetic rats treated with insulin (2 IU/day), SOV (0.6 mg/ml),T. f. graecum seed powder (TSP, 5%) and TSP (5%) in combination with lowered dose of vanadium SOV (0.2 mg/ml), for a period of 3 weeks. The activity of the enzymes, hexokinase, aldose reductase and sorbitol dehydrogenase was significantly increased whereas the activity of glucose-6-phosphate dehydrogenase, glutathione peroxidase and glutathione reductase decreased significantly in lenses from 3 week diabetic rats. Significant increase in accumulation of metabolites, sorbitol, fructose, glucose was found in diabetic lenses. TBARS measure of peroxidation increased whereas the levels of antioxidant GSH decreased significantly in diabetic condition. Insulin restored the levels of altered enzyme activities and metabolites almost to control levels. Sodium orthovanadate (0.6 mg/ml) andTrigonella administered separately to diabetic animals could partially reverse the diabetic changes, metabolic and morphological, while vanadate in lowered dose in combination withTrigonella was found to be the most effective in restoring the altered lens metabolism and morphological appearance in diabetes. It may be concluded that vanadate at lowered doses administered in combination withTrigonella was the most effective in controlling the altered glucose metabolism and antioxidant status in diabetic lenses, these being significant factors involved in the development of diabetic complications, that reflects in the reduced lens opacity     

In vitro inhibition of lens aldose reductase by (2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-yl)-acetic acid in enzyme preparations isolated from diabetic rats

(2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-yl)-acetic acid (compound 1), a novel aldose reductase inhibitor, was assayed for efficacy and selectivity to inhibit rat lens aldose reductase under in vitro conditions by using enzyme preparations obtained from diabetic animals. The inhibitory efficiency was characterized by IC(50) in micromolar region. Enzyme kinetics analysis revealed uncompetitive type of inhibition, both in relation to the D,L-glyceraldehyde substrate and to the NADPH cofactor. In testing for selectivity, comparisons to rat kidney aldehyde reductase, an enzyme with the highest homology to aldose reductase, was used. The inhibition selectivity of the compound tested was characterized by selectivity factor around 20 and was even slightly improved under conditions of prolonged experimental diabetes. These findings were identical with those in the control rats. To conclude, the inhibitory mode, efficacy and selectivity of compound 1, a novel aldose reductase inhibitor, was preserved even under the conditions of prolonged STZ-induced experimental diabetes of rats.     

Effects of total parenteral nutrition on rat bile canaliculi: a stereologic analysis

OBJECTIVE: To quantitate, in a stereologic manner, changes in bile canalicular morphology before and after choleretic infusion of total parenteral nutrition (TPN) and to determine whether TPN produces changes in localized regions within the hepatic lobule. STUDY DESIGN: Livers were obtained from sham-operated on normal adult male rats (control) and from rats that received intravenous TPN solution containing 20% glucose and 3.5% Molipron F. The tissues, obtained by a rigorous sampling procedure, were systematically subjected to stereologic analysis. Measurements were made on electron micrographs at two levels of magnification by point, intersection and profile counts, and then volume, surface area and length were estimated per unit parenchymal volume. RESULTS: The surface area of the canalicular wall per parenchymal volume increased significantly (from 5.33 x 10(-2) to 6.73 x 10(-2) microns 2/micron 3) after TPN treatment, as did the length of microvilli (from 0.241 to 0.267 microns/micron 3). However, the volume of bile canalicular lumina per parenchymal volume (0.306% and 0.320%), total length of bile canaliculi (1.05 x 10(-2) and 1.06 x 10(-2) microns/micron 3) and diameter of microvilli (8.73 x 10(-2) and 8.94 x 10(-2) microns) remained constant. CONCLUSION: These results indicate that changes in canalicular shape and microvillus hypertrophy may cause lowering efficiency of the bile flow rate.     

Efficacy of glucose, ouabain and an aldose reductase inhibitor on 2-[3H] myo-inositol uptake by human, rat and rabbit erythrocytes

Myo-inositol uptake by erythrocytes from humans, rabbits and rats was studied with an isotope technique. In human erythrocytes, the inhibitory effect on myo-inositol uptake was stronger with glucose than with ouabain. However, an aldose reductase inhibitor (ONO-2235, 100 microM) or insulin (200 microU/ml) failed to correct the decrease in myo-inositol uptake in packed RBC, produced by either 10 mM glucose or 2mM ouabain. Ten mM ouabain had an inhibitory effect on myo-inositol uptake in all species, but an inhibitory effect was not observed with 20 mM glucose in rabbit erythrocytes. The results suggest that myo-inositol uptake by erythrocytes may be dependent on the active transport system via sodium-ATPase and that erythrocytes may not be a suitable model to monitor the possible effect of an aldose reductase inhibitor on myo-inositol concentrations in other tissues concerned with diabetic complications.     

Effect of Conduritol A,a Polyol from Gymnema sylvestre,on the Development of Diabetic Cataracts in Streptozotocin-treated Rats and on Aldose Reductase

Streptozotocin-diabetic rats were maintained on a stock diet for 16 weeks and some were given conduritol A (10 mg/kg/day). The administration of conduritol A, having a hypoglycemic effect, markedly prevented the diabetic rats from getting cataracts. In practice, conduritol A inhibited aldose reductase (EC 1.1.1.21) that is capable of catalyzing the conversion of aldoses to sugar alcohols in the polyol pathway. In an in vitro assay, lens aldose reductase was most effectively inhibited by conduritol A when α,β-d-glucose was used as a substrate. Some enzymes from the rats were not inhibited by conduritol A. Neither an intraperitoneal injection nor oral dosage of conduritol A caused acute toxicity in the rats. These findings suggest that the inhibition of lens aldose reductase by conduritol A may be responsible for its cataract-suppressing effect.     

A COMPARATIVE STUDY OF THE ULTRASTRUCTURE OF MICROVILLI IN THE EPITHELIUM OF SMALL AND LARGE INTESTINE OF MICE

A comparative analysis of the fine structure of the microvilli on jejunal and colonic epithelial cells of the mouse intestine has been made. The microvilli in these two locations demonstrate a remarkably similar fine structure with respect to the thickness of the plasma membrane, the extent of the filament-free zone, and the characteristics of the microfilaments situated within the microvillous core. Some of the core microfilaments appear to continue across the plasma membrane limiting the tip of the microvillus. The main difference between the microvilli of small intestine and colon is in the extent and organization of the surface coat. In the small intestine, in addition to the commonly observed thin surface "fuzz," occasional areas of the jejunal villus show a more conspicuous surface coat covering the tips of the microvilli. Evidence has been put forward which indicates that the surface coat is an integral part of the epithelial cells. In contrast to the jejunal epithelium, the colonic epithelium is endowed with a thicker surface coat. Variations in the organization of the surface coat at different levels of the colonic crypts have also been noted. The functional significance of these variations in the surface coat is discussed.     

Differential influence of increased polyol pathway on protein kinase C expressions between endoneurial and epineurial tissues in diabetic mice

To explore the relationship between polyol pathway and protein kinase C (PKC), we examined PKC activities and expressions of PKC isoforms separately in endoneurial and vessel-rich epineurial tissues in diabetic mice transgenic for human aldose reductase (Tg). Tg and littermate control mice (Lm) were made diabetic by streptozotocin at 8 weeks of age and treated orally with aldose reductase inhibitor (ARI) (fidarestat 3-5 mg/kg/day) or placebo for 12 weeks. At the end, compared with non-diabetic state, sorbitol contents were increased 6.4-fold in endoneurium and 5.1-fold in epineurium in diabetic Tg, whereas the increase was detected only in endoneurium in diabetic Lm. Endoneurial PKC activity was significantly reduced in diabetic Tg. By contrast, epineurial PKC activity was increased in both diabetic Lm and diabetic Tg and there was no significant difference between the two groups. These changes were all corrected by ARI treatment. Consistent with the changes of PKC activities, diabetic Tg showed decreased expression of PKC alpha in endoneurium, whereas there was an increased expression of PKC beta II in epineurium in both diabetic Tg and diabetic Lm. These findings suggest the presence of dichotomous metabolic pathway between neural and vascular tissues in the polyol-PKC-related pathogenesis of diabetic neuropathy.     

Screening of Korean forest plants for rat lens aldose reductase inhibition

Naturally occurring substances which can prevent and treat diabetic complications were sought by examining ethanol extracts prepared from Korean forest plants for their inhibitory effects on rat lens aldose reductase activity in vitro. Among the plants examined, Acer ginnala, Illicium religiosum and Cornus macrophylla exerted the most strong inhibitory activity on aldose reductase.     

Polyol pathway in tissues of spontaneously diabetic Chinese hamsters (Cricetulus griseus) and the effect of an aldose reductase inhibitor, ONO-2235

1. Sorbitol and fructose levels were significantly elevated in the lens, the sciatic nerve, the retina and the kidney of diabetic Chinese hamsters and inositol level was significantly decreased in the lens and sciatic nerve of diabetics. 2. The activity of an aldose reductase in the kidney was not different between normal and diabetic Chinese hamsters. 3. An aldose reductase inhibitor (ONO-2235) had no effect in sorbitol, fructose and inositol contents of all these tissues from diabetic Chinese hamsters. 4. These results suggest that diabetic Chinese hamsters produce polyol accumulation in tissues but that there is a clear species-specific difference to inhibition of aldose reductase.