Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing diabetic nephropathy in mice.

Aminoguanidine inhibits the formation of advanced glycation end-products, and has been extensively examined in animals. However, administration of aminoguanidine decreases the hepatic content of pyridoxal phosphate. In order to avoid this problem, we developed an aminoguanidine pyridoxal Schiff base adduct and examined its efficacy in vitro as well as in a model of diabetic nephropathy. Mice with streptozotocin-induced diabetes were treated with aminoguanidine or aminoguanidine pyridoxal adduct for 9 weeks. An in vitro study was also performed to assess the antioxidant activity of aminoguanidine and its pyridoxal adduct. Neither drug altered glycemic control. Aminoguanidine pyridoxal adduct significantly improved urinary albumin excretion by 78.1 % compared with the diabetic control, and also had a better preventive effect on the progression of renal pathology than aminoguanidine did. Inhibition of glycation by both drugs was similar, but the antioxidant activity of the pyridoxal adduct was far superior. These findings suggest that aminoguanidine pyridoxal adduct may be superior to aminoguanidine, as it not only prevents vitamin B6 deficiency but is also better at controlling diabetic nephropathy, as this adduct inhibits oxidation as well as glycation.     

Pyridoxal-aminoguanidine adduct is more effective than aminoguanidine in preventing neuropathy and cataract in diabetic rats.

We examined the ability of a pyridoxal-aminoguanidine adduct with both antiglycation and antioxidant activities in vitro to protect against neuropathy and cataract in streptozotocin-diabetic rats and compared the result with that of aminoguanidine. In vivo antiglycation and antioxidant activities were also compared between the adduct and aminoguanidine. Diabetic rats were given either of the compounds in their drinking water (9 mM) for 7 weeks. Neither compound affected body weight, blood glucose level or urine volume. The adduct, but not aminoguanidine, significantly improved motor nerve conduction velocity. The time to develop cataract was longer in adduct-treated rats than in untreated and aminoguanidine-treated rats. The increase in opacification of lenses in culture medium containing high glucose levels (55.5 mM) was more efficiently attenuated by the adduct than by aminoguanidine. Adduct and aminoguanidine similarly lowered glycated hemoglobin levels. The level of urinary 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage, and the level of liver malondialdehyde plus 4-hydroxy-2-alkenals, a marker of tissue lipid peroxidation, both of which were elevated by diabetes, were significantly reduced by the adduct but not by aminoguanidine. These findings indicate that the pyridoxal-aminoguanidine adduct is superior to aminoguanidine in preventing diabetic neuropathy and cataracts, and we suggest that this may be at least partly due to the higher antioxidant activity of the former.     

Antioxidative and anti-diabetic effects of amaranth (Amaranthus esculantus) in streptozotocin-induced diabetic rats

The anti-diabetic and antioxidative effect of amaranth grain (AG) and its oil fraction (AO) was studied in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into four groups after induction of STZ-diabetes: normal control; diabetic control; diabetic-AG supplement (500 g kg(-1) diet); diabetic-AO supplement (100 g kg(-1) diet) and fed experimental diets for 3 weeks. Serum glucose, insulin, activities of serum marker enzymes of liver function and liver cytosolic antioxidant enzymes were measured. The AG and AO supplement significantly decreased the serum glucose and increased serum insulin level in diabetic rats. Serum concentration of liver function marker enzymes, GOT and GPT, were also normalized by AG and AO treatment in diabetic rats. Liver cytosolic SOD and GSH-reductase activities were significantly increased, and catalase, peroxidase and GSH-Px activities were decreased in diabetic rats. AG and AO supplement reverted the antioxidant enzyme activities to near normal values. Hepatic lipid peroxide product was significantly higher, and GSH content was decreased in diabetic rats. However, AG and AO supplement normalized these values. Our data suggest that AG and AO supplement, as an antioxidant therapy, may be beneficial for correcting hyperglycaemia and preventing diabetic complications.     

Antidiabetic and Antioxidant Effects and Phytochemicals of Mulberry Fruit (Morus alba L.) Polyphenol Enhanced Extract

The antidiabetic and antioxidant activities of the ethyl acetate-soluble extract (MFE) of mulberry fruit (Morus alba L.) were investigated. In vitro, MFE showed potent α-glucosidase inhibitory activity and radical-scavenging activities against DPPH and superoxide anion radicals. In vivo, MFE could significantly decrease fasting blood glucose (FBG) and glycosylated serum protein (GSP), and increase antioxidant enzymatic activities (SOD, CAT, GSH-Px) in streptozotocin (STZ)-induced diabetic mice. Bioactivity-guided fractionation of the MFE led to the isolation of 25 phenolic compounds, and their structures were identified on the basis of MS and NMR data. All the 25 compounds were isolated from mulberry fruit for the first time. Also, the α-glucosidase inhibitory activity and antioxidant activity of the phenolics were evaluated. Potent α-glucosidase inhibitory and radical-scavenging activities of these phenolics suggested that they may be partially responsible for the antidiabetic and antioxidant activities of mulberry fruit.     

Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide‐induced hemorrhagic cystitis in rat

Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major dose limiting side effect of CP. Recent studies show that aminogaunidine, an inhibitor of inducible nitric oxide synthase is a potent antioxidant and prevents changes caused by oxidative stress such as depletion of antioxidant activity and tissue injury. The purpose of the study is to investigate the effect of aminoguanidine on parameters of oxidative stress, antioxidant enzymes and bladder injury caused by CP. Adult male rats were randomly divided into four groups. Control rats were administered saline; the AG control group received 200 mg/kg body wt of aminoguanidine; The CP group received a single injection of CP at the dose of 150 mg/kg body wt intraperitoneally. The CP + AG group received aminoguanidine (200 mg/kg body wt) intraperitoneally 1 h before the administration of CP. The rats were sacrificed 16 h after CP/saline administration. The bladder was used for light microscopic studies and biochemical studies. The markers of oxidative damage including protein carbonyl content, protein thiol, malondialdehyde and conjugated dienes were assayed in the homogenates along with the activities of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase and glutathione S transferase. In the bladders of CP treated rats edema of lamina propria with epithelial and sub‐epithelial hemorrhage was seen. All the parameters of oxidative stress that were studied were significantly elevated in the bladders of CP treated rats. The activities of the antioxidant enzymes were significantly lowered in the bladders of CP treated rats. Aminoguanidine pretreatment prevented CP‐induced oxidative stress, decrease in the activities of anti‐oxidant enzymes and reduced bladder damage. The results of the present study suggest the antioxidant role for aminoguanidine in CP‐induced bladder damage. Copyright © 2008 John Wiley & Sons, Ltd.     

Testis glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase activities in aminoguanidine-treated diabetic rats

Severe steroidogenic and spermatogenic alterations are reported in association with diabetic manifestations in humans and experimental animals. This study was planned to determine whether oxidative stress is involved in diabetes-induced alterations in the testes. Diabetes was induced in male rats by injection of 50 mg/kg of streptozotocin (STZ). Ten weeks after injection of STZ, levels of selenium and activities of selenium dependent-glutathione peroxidase (GPx) and phospholipid hydroperoxide glutathione peroxidase (PHGPx) were measured in rat testis. Lipid and protein oxidations were evaluated as measurements of testis malondialdehyde (MDA) and protein carbonyl levels, respectively. Testis sulfydryl (SH) levels were also determined. The control levels of GPx and PHGPx activities were found to be 46.5 +/- 6.2 and 108.8 +/- 19.8 nmol GSH/mg protein/min, respectively. Diabetes caused an increase in testis GPx (65.0 +/- 21.1) and PHGPx (155.9 +/- 43.1) activities but did not affect the levels of selenium or SH. However, the testis MDA and protein carbonyl levels as markers of lipid and protein oxidation, respectively, did not increase in the diabetic group. Aminoguanidine (AG) treatment of diabetic rats returned the testis PHGPx activity (136.5 +/- 24.9) to the control level but did not change the value of GPx activity (69.2 +/- 17.4) compared with diabetic group. MDA and protein carbonyl levels in testis were not affected by AG treatment of diabetic rats, but interestingly AG caused SH levels to increase. The results indicate that reactive oxygen radicals were not involved in possible testicular complications of diabetes because diabetes-induced activations of GPx and PHGPx provided protection against oxidative stress, which was reported to be related to some diabetic complications.     

Effects of Aminoguanidine on Glomerular Basement Membrane Thickness and Anionic Charge in a Diabetic Rat Model

We investigated the effect of aminoguanidine (AG) administration on GBM thickness, glomerular heparan sulfate (HS) content, and urinary albumin and HS excretion in diabetic rats. After induction of diabetes, female Wistar rats were divided into 2 groups: Group AGDM (n=11) received 1g/L aminoguanidine bicarbonate in drinking water, group DC (n=12) was given only tap water. Control rats received AG (group AGH, n=8) or tap water (group HC, n=8). At the end of a period of 8 weeks, urinary albumin and glycosaminoglycan (GAG) excretion was detected. GBM heparan sulfate distribution and count was determined under the electron microscope. The AGDM group had lower urinary albumin and GAG excretion than diabetic controls. GBM thickness was increased in diabetic rats compared to groups of AGDM and HC. In AGDM group alcian blue stained particle distribution and count in the GBM was similar to healthy controls. In conclusion AG prevents the decrease of anionic charged molecules in the GBM and GBM thickening. This can be one of the mechanisms by which AG decreases albuminuria in diabetic rats.     

Evaluation of in vitro antioxidant activity of Indian bay leaf, Cinnamomum tamala (Buch. -Ham.) T. Nees & Eberm using rat brain synaptosomes as model system

The study investigated the perturbation of oxidant-antioxidant balance in brain synaptosomes of diabetic rats and determined the antioxidant and free radical-scavenging property of the Indian bay leaf. Brain synaptosomes were isolated from control and streptozotocin-induced diabetic animals and oxidative stress parameters were assayed. A methanolic extract of bay leaf (BLE) was tested for the polyphenolic content and antioxidant activity by in vitro assays. A significant increase in the levels of lipids and lipid peroxidation products and a decline in antioxidant potential were observed in diabetic rat brain synaptosomes. The total polyphenolic content of BLE was found to be 6.7 mg gallic acid equivalents (GAE)/100g. BLE displayed scavenging activity against superoxide and hydroxyl radicals in a concentration-dependent manner. Further, BLE showed inhibition of Fe(2+)-ascorbate induced lipid peroxidation in both control and diabetic rat brain synaptosomes. Maximum inhibition of lipid peroxidation, radical scavenging action and reducing power of BLE were observed at a concentration of 220 microg GAE. These effects of BLE in vitro were comparable with that of butylated hydroxyl toluene (BHT), a synthetic antioxidant. It can be concluded that synaptosomes from diabetic rats are susceptible to oxidative damage and the positive effects of bay leaf in vitro, could be attributed to the presence of antioxidant phytochemicals.     

2,2′-Dipyridyl diselenide is a better antioxidant than other disubstituted diaryl diselenides

The aim of this study was to investigate the in vitro antioxidant activity of 2,2'-dipyridyl diselenide (e) by comparing this effect with m-trifluoromethyl-diphenyl diselenide (a), p-fluor-diphenyl diselenide (b), p-chloro-diphenyl diselenide (c), and p-methoxyl-diphenyl diselenide (d) in rat liver homogenate. We also investigated if the mechanisms involved in the antioxidant property of 2,2'-dipyridyl diselenide are the same that of other diselenides. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl (PC) levels were determined in rat liver homogenate, as indicators of antioxidant activity. Dehydroascorbate (DHA) reductase- and glutathione S-transferase (GST)-like activities, 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical-scavenging activities and the protection against the oxidation of Fe(2+) were determined to better understand the antioxidant property of compounds. δ-Aminolevulinic dehydratase (δ-ALA-D) activity was also carried out in rat liver homogenates, as a toxicological parameter. Compound e showed the highest potency in reducing TBARS (order of IC(50) values: e < b ≤ a < d ≤ c) and PC (order of IC(50) values: e < c ≤ b ≤ a < d) levels and lower potency in inhibiting δ-ALA-D activity than other diselenides. Compound e at all concentrations tested had no enzyme-mimetic property, but had radical-scavenging activity (≥5 μM) and protected against the oxidation of Fe(2+) (50 μM); while compounds a-d showed GST and DHA-mimetic activities and protected against the oxidation of Fe(2+), but had not radical-scavenging activities. This study indicates that (i) 2,2'-dipyridyl diselenide (e) had better in vitro antioxidant effect than other diselenides and lower inhibitory effect on δ-ALA-D activity, (ii) the presence of pyridine ring is responsible for the best antioxidant effect of this compound, and (iii) 2,2'-dipyridyl diselenide acts by different mechanisms of other diselenides.     

Mechanisms of salt-sensitive hypertension: role of inducible nitric oxide synthase

The goal of this study was to determine the role of inducible nitric oxide synthase (iNOS) in the arterial pressure, renal hemodynamic, renal excretory, and hormonal changes that occur in Dahl/Rapp salt-resistant (R) and salt-sensitive (S) rats during changes in Na intake. Thirty-two R and S rats, equipped with indwelling arterial and venous catheters, were subjected to low (0.87 mmol/day) or high (20.6 mmol/day) Na intake, and selective iNOS inhibition was achieved with intravenous aminoguanidine (AG, 12.3 mg. kg(-1). h(-1)). After 5 days of AG, mean arterial pressure increased to 121 +/- 3% control in the R-high Na AG rats compared with 98 +/- 1% control (P < 0.05) in the R-high Na alone rats, and S-high Na rats increased their arterial pressure to 123 +/- 3% control compared with 110 +/- 2% control (P < 0.05) in S-high Na alone rats. AG caused no significant changes in renal hemodynamics, urinary Na or H(2)O excretion, plasma renin activity, or cerebellar Ca-dependent NOS activity. The data suggest that nitric oxide produced by iNOS normally helps to prevent salt-sensitive hypertension in the Dahl R rat and decreases salt sensitivity in the Dahl S rat.     

Effects of aminoguanidine against renal ischaemia-reperfusion injury in rats

Aminoguanidine is an inhibitor of nitric oxide synthase (NOS), with high selectivity for the inducible isoform (iNOS). In addition to being an inhibitor of NOS, aminoguanidine also exhibits antioxidant activity. Recent studies suggest that aminoguanidine reduces ischaemia-reperfusion (I/R)-induced damage. However, the role of aminoguanidine, in renal injury associated with I/R remains unknown. This study was designed to investigate the effects of aminoguanidine on renal I/R injury. There were three groups of eight rats each. I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24 h reperfusion in rats. Malondialdehyde (MDA) levels, a stable metabolite of the free radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (30.3 +/- 0.1 nmol g(-1) tissue) than in the control group (10 +/- 0.05 nmol g(-1)). Aminoguanidine (100 mg kg(-1)) administration to rats significantly reduced the MDA values. We also demonstrated that I/R leads to structural change but aminoguanidine did not reverse this change. Aminoguanidine, according to the biochemical finding is protective but histopathological findings did not reveal protection against I/R injury in kidney. The effects of aminoguanidine on I/R-induced damage remain a subject for future investigations.     

Antioxidant potential of Coriandrum sativum L. seed extract

The seeds of C. sativum are used as a traditional drug for the treatment of diabetes. The antioxidant and free-radical-scavenging property of seeds in vitro was studied and also investigated whether the administration of seeds curtails oxidative stress in the kidney of streptozotocin-induced diabetic rats. Incorporation of seed powder in the diet led to marked lowering of blood glucose and a rise in the levels of insulin in diabetic rats. A parallel beneficial effect was observed on oxidant -antioxidant balance in the kidney. Addition of coriander seed powder not only inhibited the process of peroxidative damage but also significantly reactivated the antioxidant enzymes and antioxidant levels in diabetic rats. The total polyphenolic content of the seeds was found to be 12.2 gallic acid equivalents (GAE)/g while total flavanoid content was found to be 12.6 quercetin equivalents/g. The seeds also showed scavenging activity against superoxides and hydroxyl radicals in a concentration-dependent manner. Maximum free radical-scavenging action and free radical reducing power of coriander seed extract was observed at a concentration of 50 microg GAE. Islet histology structures showed degeneration of pancreatic islets in diabetic rats which was also reduced in diabetic rats treated with seed powder. These results show that C. sativum seeds not only possess antihyperglycemic properties but antioxidative properties also. Increased dietary intake of coriander seeds decrease the oxidative burden in diabetes mellitus.     

Experimental diabetes causes mitochondrial loss and cytoplasmic enrichment of pyridoxal phosphate and aspartate aminotransferase activity

The streptozotocin diabetic rat was selected as a model to study how insulin deficiency alters vitamin B6 utilization by focusing on pyridoxal phosphate levels and aspartate aminotransferase activities in liver tissues. Diabetes of 15 weeks' duration lowered plasma pyridoxal phosphate levels by 84%. Normal plasma pyridoxal phosphate was 480 pmole/ml. Fractionation of liver into mitochondrial and extramitochondrial compartments demonstrated that diabetes caused a 43% diminution in mitochondrial pyridoxal phosphate per gram of liver. There was no cytoplasmic change in these diabetic rats. Mitochondrial aspartate aminotransferase activity was decreased 53% per gram of diabetic liver and cytoplasmic aspartate aminotransferase activity was elevated 3.4-fold. Damage to diabetic mitochondria during preparation procedures could not account for the rise in cytoplasmic aspartate aminotransferase activity. Electrophoresis showed that in the diabetic cytoplasm both cathodal and anodal forms of the enzyme were elevated. Speculations concerning mitochondrial loss and cytoplasmic gain of enzyme activity as well as those on the reduction of plasma pyridoxal phosphate in the diabetic rat are presented.     

Effects of chronic inhibition of inducible nitric oxide synthase in hyperthyroid rats

We hypothesized that nitric oxide generated by inducible nitric oxide synthase (iNOS) may contribute to the homeostatic role of this agent in hyperthyroidism and may, therefore, participate in long-term control of blood pressure (BP). The effects of chronic iNOS inhibition by oral aminoguanidine (AG) administration on BP and morphological and renal variables in hyperthyroid rats were analyzed. The following four groups (n = 8 each) of male Wistar rats were used: control group and groups treated with AG (50 mg.kg(-1).day(-1), via drinking water), thyroxine (T4, 50 microg.rat(-1).day(-1)), or AG + T4. All treatments were maintained for 3 wk. Tail systolic BP and heart rate (HR) were recorded weekly. Finally, we measured BP (mmHg) and HR in conscious rats and morphological, plasma, and renal variables. T(4) administration produced a small BP (125 +/- 2, P < 0.05) increase vs. control (115 +/- 2) rats. AG administration to normal rats did not modify BP (109 +/- 3) or any other hemodynamic variable. However, coadministration of T4 and AG produced a marked increase in BP (140 +/- 3, P < 0.01 vs. T4). Pulse pressure and HR were increased in both T4- and T4 + AG -treated groups without differences between them. Plasma NOx (micromol/l) were increased in the T4 group (10.02 +/- 0.15, P < 0.05 vs. controls 6.1 +/- 0.10), and AG reduced this variable in T4-treated rats (6.81 +/- 0.14, P < 0.05 vs. T4) but not in normal rats (5.78 +/- 0.20). Renal and ventricular hypertrophy and proteinuria of hyperthyroid rats were unaffected by AG treatment. In conclusion, the results of the present paper indicate that iNOS activity may counterbalance the prohypertensive effects of T4.     

Effect of inhibition of synthesis of inducible nitric oxide synthase-derived nitric oxide by aminoguanidine on the in vitro maturation of oocyte-cumulus complexes of cattle

The aim of the present study was to investigate the effects of inhibition of the enzyme inducible nitric oxide synthase (iNOS) by aminoguanidine (AG) on the in vitro maturation of oocyte-cumulus cell complex(es) (COC) of cattle. COC were cultured with different concentrations of AG (0, 1, 10, and 100mM) for 24h. In Experiment 1, the extent of cumulus complex expansion, nuclear maturation status and plasma membrane integrity of oocytes and cumulus cells from each treatment were assessed. Nitrate/nitrite (NO(3)(-)/NO(2)(-)) concentrations were determined in culture medium by the Griess method. Addition of different concentrations of AG to maturation medium promoted a dose-response inhibitory effect on cumulus expansion (P<0.05). Addition of 1 and 10mM AG to IVM medium did not affect plasma membrane integrity of oocytes or nuclear maturation rates (P>0.05), but it did reduce plasma membrane integrity in cumulus cells. One hundred millimolar inhibited pre-metaphase I (pre-MI) to metaphase II (MII) transition, promoted plasma membrane damage in oocytes (P<0.05), and increased NO(3)(-)/NO(2)(-) concentration when compared to controls (P<0.05). To evaluate if this effect was reversible, 10(-5)M sodium nitroprusside (SNP, NO donor) was added, only in the treatment with 100mM AG that inhibited the nuclear maturation. However, association of 10(-5)M SNP to 100mM AG did not reverse the effects of AG, but increased NO(3)(-)/NO(2)(-)concentration (P<0.05). In Experiment 2, the effect of different AG concentrations on cytoplasmic maturation in vitro was assessed based on cortical granule migration, and embryonic development. There was a dose effect on cortical granule migration rate, in which 1mM AG (83.9+/-6.2%) did not differ from control oocytes (83.6+/-8.2%; P>0.05), but 10mM partially inhibited migration (3.8+/-6.4%) and 100mM totally inhibited migration (P<0.05). SNP (10(-5)M) did not revert this inhibitory effect on cortical granules migration in oocytes treated with 100mM AG. Only those concentrations that did not inhibit IVM were used to assess cleavage and blastocyst development. Addition of 10mM AG to IVM medium reduced (73.0+/-8.1%, 15.0+/-8.9%; P<0.05) cleavage and blastocyst development, respectively when compared with controls (89.1+/-3.4%, 37.6+/-7.3%, respectively), but did not differ, (P>0.05), from the group treated with 1mM AG (80.9+/-8.4%, 41.5+/-10.5%, respectively). The results from the present study demonstrate that NO derived from iNOS affects the in vitro maturation of bovine COC, modulating the viability of cumulus cells and of oocyte, the progression of meiosis after GVBD, the migration of cortical granules, and cleavage and blastocyst development.     

Physiological activities of a β-glucan produced by Panebacillus polymyxa

In vitro bioactivities of a beta-glucan produced by Panebacillus polymyxa JB115 were investigated. Nitric oxide production by RAW 264.7 macrophage cells pre-treated with beta-glucan JB115 (from 0.1 to 1 mg ml(-1)) was significantly increased, compared to that in untreated cells (P < 0.001). The beta-glucan JB115 increased superoxide radical-scavenging activity by 66% at 1 mg ml(-1). It also suppressed hyaluronidase (32%) and collagenase (33%) activities and, additionally, displayed antitumor activity, blocking the growth of Sarcoma 180 cells in a concentration-dependent manner. The immune-stimulatory, antioxidant, collagenase inhibitory and hyaluronidase inhibitory effects of the beta-glucan support its potential role in the prevention of bacterial disease against fish and in the protection of skin against aging.     

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.     

Antioxidant activity in vitro of two aromatic compounds from Caesalpinia sappan L

Two antioxidant compounds were isolated from C. sappan L by multiple steps of column chromatography and thin layer chromatography in succession with superoxide scavenging assay as activity monitor. Structures of the two compounds were determined by spectroscopic methods as 1',4'-dihydro-spiro[benzofuran-3(2H),3'-[3H-2]benzopyran]-1',6',6',7'-tetrol (compound 1) and 3-[[4,5-dihydroxy-2(hydroxymethyl) phenyl]-methyl]-2,3-dihydro-3,6-benzofurandiol (compound 2). Characterization of antioxidant properties of these two compounds was done by determining the inhibitory effect on xanthine oxidase activity as well as scavenging effect on superoxide anion and hydroxyl radicals. Our results indicated that compounds 1 and 2 inhibited xanthine oxidase activity and scavenged superoxide anion and hydroxyl radicals. Compounds 1 and 2 possessed similar radical scavenging activities as ascorbic acid, and they were more effective than other well-known antioxidants such as alpha-tocopherol, beta-carotene, and BHT. As inhibitors of free radical formation, compounds 1 and 2 were more effective than all the other antioxidants tested. In conclusion, compounds 1 and 2 can be regarded as primary antioxidants with radical-scavenging and chain-breaking activities as well as secondary antioxidants with inhibitory effect on radical generation.     

川芎嗪联合氨胍治疗对糖尿病大鼠视网膜血管内皮生长因子表达的影响

目的 观察川芎嗪联合氨胍治疗对糖尿病大鼠视网膜血管内皮生长因子（VEGF）表达的影响。探讨川芎嗪联合氨胍治疗糖尿病视网膜病变（DR）的机制。方法 应用链尿佐菌素（STZ）制作糖尿病大鼠模型。分为正常对照组,糖尿病未治疗组,川芎嗪治疗组,氨胍治疗组和川芎嗪联合氨胍治疗组,分别于第4周,第12周和第20周应用免疫组化方法观察各组大鼠视网膜组织VEGF表达的变化。结果 正常大鼠视网膜组织VEF表达仅见于内核层,糖尿病大鼠视网膜组织VEGF阳性表达随周龄的延长而增强,且在毛细血管内和节细胞层可见VEGF表达,治疗12周和20周后,川芎嗪治疗组和氨胍治疗组大鼠视网膜组织VEGF阳性表达比未治疗组明显减弱,但仍高于正常对照组,而川芎嗪联合氨胍治疗组视网膜组织VEGF表达接近正常。结论 川芎嗪联合氨胍治疗可抑制糖尿病大鼠视网膜VEGF的过度表达。是川芎嗪联合氨胍治疗糖尿病视网膜病变（DR）的机制之一。     

Aminoguanidine decreases urinary albumin and high-molecular-weight proteins in diabetic rats

The effect of aminoguanidine (AG) on diabetic proteinuria was studied in control rats ([C]), streptozotocin (SZ)-induced diabetic rats ([DM]), control rats treated with AG [( C + AG]), or diabetic rats treated with AG [( DM + AG]). Increased glycation of hemoglobin (HbA1C), and glomerular basement membrane (GBM) type IV collagen (IV-C) at 10 wk of stable diabetes were associated with the appearance of high-molecular-weight (HMW) cross-linked type I collagen and HMW proteinuria of 62 kD, 69 kD albumin and 77 kD proteins to the levels of 362, 381, and 408%, while 9.9, 13.5, 17, 18, and 23 kD proteins were decreased, respectively, to non-detectable, 37, 16, and 13%. AG decreased cross-linkage of type I collagen and significantly decreased urinary 62 kD protein to 54%, 69 kD albumin to 40%, and 77 kD protein to 49% at 10 wk in [DM + AG] compared to [DM] without changing diabetic control. It is suggested that glycation-derived late-stage protein modification is etiologically important for diabetic proteinuria, and that AG can potentially prevent diabetic HMW proteinuria.