异甘草酸镁对纤维化大鼠肝脏TGF-β 1及Smad蛋白表达的影响

目的：观察异甘草酸镁对四氯化碳诱导的肝纤维化大鼠肝脏组织TGF-β1及Smad蛋白表达的影响,以期揭示其抗纤维化的机制。方法：利用腹腔注射四氯化碳（CCl4）建立大鼠肝纤维化模型,然后应用不同剂量的异甘草酸镁和INF-γ处理,于实验第16周末检测大鼠血清透明质酸（HA）、层粘连蛋白（LN）、III型前胶原（PC-III）、IV型胶原（C-IV）的水平,采用RT-PCR法检测TGF-β1,Smad3,Smad7mRNA的表达。结果：与模型组比较,异甘草酸镁各剂量组血清HA,LN,PC-III,C-IV水平显著下降（P〈0.05）,肝脏TGF-β1、smad3的表达明显降低（P〈0.05）,smad7则有所上升。结论：异甘草酸镁可以改善肝纤维化大鼠肝组织纤维化程度,其作用机理与抑制TGF-β1、Smad3mRNA的表达,上调Smad7mRNA的表达有密切关系。     

Duration of streptozotocin-induced diabetes differentially affects p38-mitogen-activated protein kinase (MAPK) phosphorylation in renal and vascular dysfunction

Background

In the present study we tested the hypothesis that progression of streptozotocin (STZ)-induced diabetes (14-days to 28-days) would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK) phosphorylation in kidneys and thoracic aorta.

Methods

Male Sprague Dawley rats (350–400 g) were randomized into three groups: sham (N = 6), 14-days diabetic (N = 6) and 28-days diabetic rats (N = 6). Diabetes was induced using a single tail vein injection of STZ (60 mg/kg, I.V.) on the first day. Rats were monitored for 28 days and food, water intake and plasma glucose levels were noted. At both 14-days and 28-days post diabetes blood samples were collected and kidney cortex, medulla and aorta were harvested from each rat.

Results

The diabetic rats lost body weight at both 14-days (-10%) and 28-days (-13%) more significantly as compared to sham (+10%) group. Glucose levels were significantly elevated in the diabetic rats at both 14-days and 28-days post-STZ administration. Renal dysfunction as evidenced by renal hypertrophy, increased plasma creatinine concentration and reduced renal blood flow was observed in 14-days and 28-days diabetes. Vascular dysfunction as evidenced by decreased carotid blood flow was observed in 14-days and 28-days diabetes. We observed an up-regulation of inducible nitric oxide synthase (iNOS), prepro endothelin-1 (preproET-1) and phosphorylated p38-MAPK in thoracic aorta and kidney cortex but not in kidney medulla in 28-days diabetes group.

Conclusion

The study provides evidence that diabetes produces vascular and renal dysfunction with a profound effect on signaling mechanisms at later stage of diabetes.     

Metallothionein mRNA levels are influenced by dietary cyclodextrins in rats

The relationship between metallothionein mRNA levels and the amounts of copper and zinc in liver, kidney and small intestine by feeding dietary cyclodextrin was examined in growing Wistar rats. alpha-, beta- or gamma-cyclodextrin was fed at 50 g/kg of diet for a 7-days period (ad libitum). After feeding, the liver zinc of rats fed beta-cyclodextrin was greater than those of rats fed the other three diets. Copper accumulated in kidney of rats fed alpha- or beta-cyclodextrin. Copper content in the small intestine did not show any alterations among rats fed all kinds of diets. The cyclodextrin-supplemented diets were ineffective in zinc content in every organ. There was the greatest level of copper in serum of rats fed beta-cyclodextrin, whereas the highest level of serum zinc was observed in rats fed gamma-cyclodextrin diet. Northern blot analysis demonstrated that dietary beta- and gamma-cyclodextrins, but not alpha-cyclodextrin markedly increased the metallothionein mRNA in the liver, whereas small intestinal metallothionein mRNA levels were markedly decreased. Kidney metallothionien mRNA levels were raised appreciably by all dietary cyclodextrin intakes. Metallothionein gene expressions in liver, kidney and small intestine were not proportional to liver and serum copper or zinc levels in those tissues. These results suggest that regulation of the metallothionein mRNA levels may at least partly involved with the accumulation of metals as copper in liver and kidney of rats fed cyclodextrins.     

Increased level of glycoxidation product N(epsilon)-(carboxymethyl)lysine in rat serum and urine proteins with aging: link with glycoxidative damage accumulation in kidney

Accumulation of carboxymethylated proteins (CML-proteins) is taken as a biomarker of glycoxidative stress which is thought to contribute to the age-related impairment in tissue and cell function. To investigate the occurrence and extent of glycoxidative damage with aging in rat kidney, serum and urine, we have prepared a polyclonal antibody against CML-modified bovine serum albumin. We subsequently used it for immunolocalization and in enzyme-linked immunosorbent assays to evaluate CML-protein content. In the serum, CML-protein level was 1.43+/-0.14 pmol CML/micrograms protein at 3 months and significantly increased by 50% from 10 to 27 months (1.50+/-0.14 pmol CML/micrograms protein vs 2.27+/-0.26 pmol CML/micrograms protein), albumin and transferrin being the main modified proteins. In the urine, CML-protein level was 2.50+/-0.14 pmol CML/micrograms protein at 3 months and markedly increased from 10 months (2.99+/-0.24 pmol CML/micrograms protein) to 27 months (3.76+/-0.25 pmol CML/micrograms protein), with albumin as the main excreted modified protein. Immunolocalization of CML-proteins in kidney provided evidence for an age-dependent increased accumulation in extracellular matrices. Intense staining of the glomerular basement membrane (GBM), Bowman's capsule, and the tubular basement membrane was found. Additionally, the CML content for collagen from GBM was 195.85+/-28.95 pmol CML/microgrms OHPro at 3 months and significantly increased from 10 months (187.61+/-21.99 pmol CML/micrograms OHPro) to 27 months (334.55+/-62.21 pmol CML/micrograms OHPro). These data show that circulating CML-protein level in serum and urine and CML accumulation in nephron extracellular matrices with aging are increasing in parallel. The CML-protein measurement in serum and urine may thus be used as an index for the assessment of age-associated glycoxidative kidney damage.     

Melatonin reduces oxidative stress induced by ochratoxin A in rat liver and kidney

Melatonin (MEL) displays antioxidant and free radical scavenger properties. In the present study, the effect of MEL on the oxidative stress induced by ochratoxin A (OTA) administration in rats was investigated. Four groups of 15 rats each were used: controls, MEL-treated rats (5 mg/kg body mass), OTA-treated rats (250 μg/kg) and MEL+OTA-treated rats. After 4 weeks of treatment, the levels of malondialdehyde (MDA), a lipid peroxidation product (LPO) were measured in serum and homogenates of liver and kidney. Also, the levels of glutathione (GSH), and activities of glutathione reductase (GR), glutathione peroxidase (GSPx), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in liver and kidney were determined. In OTA-treated rats, the levels of LPO in serum and in both liver and kidney were significantly increased compared to levels in controls. Concomitantly, the levels of GSH and enzyme activities of SOD, CAT, GSPx and GR in both liver and kidney were significantly decreased in comparison with controls. In rats received MEL+OTA, the changes in the levels of LPO in serum and in liver and kidney were not statistically significant compared to controls. Concomitantly, the levels of GSPx, GR and GST activities in both liver and kidney tissues were significantly increased in comparison with controls. Similar increases in GSPx, GR and GST activities were also observed in MEL-treated rats when compared with controls. In conclusion, the oxidative stress may be a major mechanism for the toxicity of OTA. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and stimulation of GST activities. Thus, clinical application of melatonin as therapy should be considered in cases of ochratoxicosis.     

Change of serum L-tryptophan levels following the development and recovery of acute puromycin aminonucleoside nephrosis in rats

Summary It is known that total L-tryptophan (Trp) levels decrease with a decrease in albumin-bound Trp levels and an increase in free Trp levels in the plasma or serum of nephrotic children. We, therefore, examined the change of serum Trp levels following the development and recovery of acute nephrosis in 6-week-old male Wistar rats injected once with puromycin aminonucleoside (100mg/kg body weight) and checked the levels of 16 amino acids including Trp in the serum and the levels of Trp in the liver, kidney, and urine under nephrotic conditions. In this study, the development and recovery of nephrosis were checked by the changes of levels of urinary protein and serum protein and albumin. Total serum Trp and albumin-bound serum Trp levels decreased with the development of nephrosis and these decreased levels returned to the normal level with its recovery. In contrast, free serum Trp levels increased with the development of nephrosis and this increased level returned to the normal level with its recovery. In the serum of nephrotic rats, the decrease of albumin-bound Trp levels and the increase of free Trp levels were well consistent with a decrease in albumin levels and an increase in the level of non-esterified fatty acids which are known to weaken the binding of Trp to albumin and among 16 amino acids studied, only Trp showed a significant change in its levels. Trp levels increased in the liver and kidney but not in the urine under nephrotic conditions. These results indicate that the change of serum Trp levels should be closely related to the condition of nephrosis and that although serum Trp is lost under nephrotic conditions, the lost serum Trp is accumulated in the liver and kidney.     

Thyroid status in the obese syndrome of rats

The thyroid function was explored by comparing serum total and free iodothyronine levels in young male genetically obese Zucker rats and in their lean littermates, aged from 6 to 8 weeks old. Total and free thyroxine (T4) and 3,5,3'triiodothyronine (T3) levels were significantly decreased in obese rat serum while total 3,3',5'-triiodothyronine (rT3) remained constant. Radioactive T4 half life is slower in the plasma of obese rats. Peripheral synthesis of T3 from deiodination of T4 is also decreased in obese rat liver homogenate. These modifications produce changes in liver mitochondria oxidative phosphorylation and in marker enzyme activity, which are usually associated with hypothyroidism and hypothalamic disturbances. Genetic obesity probably involves activation of peripheral deiodination of T4 to rT3 which induces biochemical and metabolic changes.     

Expression of metallothionein in the liver and kidney of rats is influenced by excess dietary histidine

It is well known that excess dietary histidine induces the metabolic changes in copper and zinc. Therefore, this study was carried out to clarify whether excess dietary histidine alters the gene expressions of metallothionein-1 and metallothionein-2 in the liver and kidney. Male rats were fed the control (ad libitum and pair-fed) or histidine-excess (50 g of L-histidine per kg of diet) diet for 0, 1 and 3 days. The levels of liver metallothionein-1 and metallothionein-2 mRNA were markedly lower in the rats fed the histidine-excess diet as compared to those of the control (ad libitum and pair-fed) diet, when fed for 1 or 3 days. The levels of renal metallothionein-1 and metallothionein-2 mRNA in the rats fed the histidine-excess diet were higher or tended to be higher as compared with the rats fed the control (ad libitum and pair-fed) diet when fed for 1 or 3 days, respectively. At the same time, hepatic copper content was decreased and renal zinc content was increased by dietary histidine. It thus appears, that such a response on the level of liver metallothionein mRNA might be related to the contents of liver copper, but of kidney metallothionein mRNA might be due to the content of zinc.     

Antioxidative and metabolic responses to extended cold exposure in rats

In this work, we investigated whether extended cold exposure increases oxidative damage and susceptibility to oxidants of rat liver, heart, kidney and lung which are metabolically active tissues. Moreover in this study the effect of cold stress on some of the lipid metabolic mediators were studied in rat experimental model. Male albino Sprague-Dawley rats were randomly divided into two groups: The control group (n=12) and the cold-stress group (n=12). Tissue superoxide dismutase (SOD), catalase (CAT), glutathion S-transferase (GST) and glutathion reductase (GR) activities and glutathion (GSH) were measured using standard protocols. The biochemical analyses for total lipid, cholesterol, trigliceride, HDL, VLDL and LDL were done on autoanalyzer. In cold-stress groups SOD activity was decreased in the lung whereas it increased in the heart and kidney. CAT activity was significantly decreased (except liver) in all the tissues in treated rats. GST activity of cold-induced rats increased in liver and heart while decreased in the lung. GR activity was significantly decreased (except in liver) in all the tissues in cold-stressed rats. GSH level was significantly increased in the heart but decreased in the lung of animals exposed to cold when compared to controls. It was found that among the groups trigliceride, total lipid, HDL and VLDL parameters varied significantly but cholesterol and LDL had no significant variance. In this study, we found that exposure of extended (48 h) cold (8 degrees C) caused changes both in the antioxidant defense system (as tissue and enzyme specific) and serum lipoprotein profiles in rats.     

Metabolic cooperation of ascorbic acid and glutathione in normal and vitamin C-deficient ODS rats.

Although the coordination of various antioxidants is important for the protection of organisms from oxidative stress, dynamic aspects of the interaction of endogenous antioxidants in vivo remain to be elucidated. We studied the metabolic coordination of two naturally occurring water-soluble antioxidants, ascorbic acid (AA) and reduced glutathione (GSH), in liver, kidney and plasma of control and scurvy-prone osteogenic disorder Shionogi (ODS) rats that hereditarily lack the ability to synthesize AA. When supplemented with AA, its levels in liver and kidney of ODS rats increased to similar levels of those in control rats. Hepato-renal levels of glutathione were similar with the two animal groups except for the slight increase in its hepatic levels in AA-supplemented ODS rats. Administration of L-buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, rapidly decreased the hepato-renal levels of glutathione in a biphasic manner, a rapid phase followed by a slower phase. Kinetic analysis revealed that glutathione turnover was enhanced significantly in liver mitochondria and renal cytosol of ODS rats. Administration of BSO significantly increased AA levels in the liver and kidney of control rats but decreased them in AA-supplemented ODS rats. Kinetic analysis revealed that AA is synthesized by control rat liver by some BSO-enhanced mechanism and the de novo synthesized AA is transferred to the kidney. Such a coordination of the metabolism of GSH and AA in liver and kidney is suppressed in AA-deficient ODS rats. These and other results suggest that the metabolism of AA and GSH forms a compensatory network by which oxidative stress can be decreased.     

高胱氨酸尿对大鼠肾脏自噬水平的抑制作用

摘要 目的：探讨胱氨酸尿症中高胱氨酸浓度对大鼠肾脏自噬水平的影响。方法：通过液相色谱串联质谱（LC-MS/MS）测定Slc7a9基因敲除大鼠24小时尿液胱氨酸浓度确定高尿胱氨酸;通过IHC（免疫组织化学）染色筛选无结石产生的胱氨酸尿症大鼠、观察肾脏组织结构有无明显变化;通过Western blot测定肾脏组织中的LC3-I、LC3-II、p62和mTOR的蛋白相对表达量,以检测自噬水平的变化,并探索变化原因;通过组织切片Masson染色法检测肾脏髓质纤维化程度。结果：10只无结石胱氨酸尿症大鼠尿液胱氨酸显著高于对照组;未发现有胱氨酸结石的生成与肾脏结构性变化;Masson染色提示胱氨酸尿症大鼠发现轻度肾脏纤维化过程;肾脏组织自噬标记蛋白LC3-I、LC3-II蛋白相对表达量、LC3-II/LC3-I比值以及自噬当量p62相对表达较对照组均显著降低,mTOR相对表达量显著升高。以上差异均有统计学意义（P＜0.05）。结论：在胱氨酸尿症大鼠模型上,发现无结石形成情况下的尿高胱氨酸水平可通过mTOR途径抑制大鼠肾脏组织的自噬水平,自我保护作用减弱,由此参与胱氨酸尿症的肾脏损伤过程。     

Effects of parathyroidectomy on tissue calcium,phosphorus, magnesium,and copper concentrations in aluminum-loaded uremic rats

Rats were subjected to a two-stage 5/6 nephrectomy and treated with Al for 2 and 4 wk with a cumulative dose of 4.2 and 8.4 mg of Al, respectively. Other animals were parathyrectomized (PTx) and loaded with 8.4 mg of Al for 4 wk. Total Al, Ca, P, Mg, and Cu contents were analyzed in the liver, kidney, and bone by inductively coupled plasma atomic emission spectrometry (ICP-AES). The results showed that Al given to growing uremic rats significantly increased the content of Al in the liver, kidney, and bone. Moreover, Al treatment increased the liver and kidney Ca levels and decreased the Ca and P values in bone. Previous parathyroidectomy significantly reduced Al accumulation within organs and changes in the Ca and P levels in the bone, liver, and kidney. The result was not influenced by different degrees of renal failure.     

Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats

Free radicals and oxidative stress have been implicated in the etiology of diabetes and its complications. This in vivo study has examined whether subacute administration of pycnogenol, a French pine bark extract containing procyanidins that have strong antioxidant potential, alters biomarkers of oxidative stress in normal and diabetic rats. Diabetes was induced in female Sprague-Dawley rats by a single injection of streptozotocin (90 mg/kg body weight, ip), resulting (after 30 days) in subnormal body weight, increased serum glucose concentrations, and an increase in liver weight, liver/body weight ratios, total and glycated hemoglobin, and serum aspartate aminotransferase activity. Normal and diabetic rats were treated with pycnogenol (10 mg/kg body weight/day, ip) for 14 days. Pycnogenol treatment significantly reduced blood glucose concentrations in diabetic rats. Biochemical markers for oxidative stress were assessed in the liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was restored to normal levels after pycnogenol treatment. Additionally, diabetic rats treated with pycnogenol had significantly elevated levels of reduced glutathione and glutathione redox enzyme activities. The results demonstrate that pycnogenol alters intracellular antioxidant defense mechanisms in streptozotocin-induced diabetic rats.     

Unusual metabolism of sulfur-containing amino acids in rats treated with DL-propargylglycine

S-(2-Hydroxy-2-carboxyethyl)homocysteine, S-(3-hydroxy-3-carboxy-n-propyl)-cysteine, N-acylated S-(beta-carboxyethyl)cysteine, and N-acylated S-(3-hydroxy-3-carboxy-n-propyl) cysteine were excreted in the urine after DL-propargylglycine treatment. Cystathionine was also accumulated in several tissues of DL-propargylglycine-treated rats. N-Monoacetylcystathione was found in the liver of rats and was also detected in the kidney and serum. Cystathionine gamma-lyase activity in liver decreased to about 4% of that of control rats 24 h after the DL-propargylglycine injection, and alanine aminotransferase activity decreased to about 35% of that of control rats. On the other hand, aspartate aminotransferase and cystathionine beta-synthese activity did not show significant changes from those of control rats. The ability of normal tissues to synthesize cystathionine utilizing cystathionine beta-synthase was 1.98 +/- 0.40 mumol/min/g in liver, 0.61 +/- 0.13 in kidney, and 0.18 +/- 0.015 in brain. The maximal contents of cystathionine in rat tissues and the administered amounts of DL-propargylglycine agreed well with the ability to synthesize cystathionine in each tissue.     

Reduced contractile response to insulin and IGF-I in ventricular myocytes from genetically obese Zucker rats

Obesity plays a pivotal role in the pathophysiology of metabolic and cardiovascular diseases. Resistance to insulin is commonly seen in metabolic disorders such as obesity and diabetes. Insulin-like growth factor-I (IGF-I) mimics insulin in many tissues and has been shown to enhance cardiac contractile function and growth. Because IGF-I resistance often accompanies resistance to insulin, we sought to determine whether IGF-I-induced myocardial contractile was elevated and whether heart and kidney size were enlarged in obese compared with lean rats. The myocyte contraction profile in the obese rats showed a decreased peak shortening associated with prolonged relengthening and normal shortening duration, a pattern similar to that observed in diabetes. IGF-I (1-500 ng/ml) caused a dose-dependent increase in peak shortening in lean but not obese animals, but it did not alter the duration of shortening and relengthening. Consistent with contractile data, IGF-I induced a dose-dependent increase in Ca(2+) transients only in myocytes of lean rats. IGF-I receptor mRNA levels were significantly reduced in obese rat hearts. These results suggest that the IGF-I-induced cardiac contractile responses are attenuated in the Zucker model of obesity. The mechanisms underlying this alteration may be related to the decreased receptor number and/or changes in intracellular Ca(2+) handling in these animals.     

Biochemical alterations induced by a new phosphorothionate (RPR-II) in tissues of male and female rats

This study was conducted to investigate the effect of a new phosphorothionate, the methyl ester of 2-butenoic acid-3-diethoxy phosphinothioyl (RPR-II) on membrane bound target enzymes aspartate amino transferase (ASAT), alanine amino transferase (ALAT) and RBC acetylcholinesterase (AChE) in different tissues of male and female albino wistar rats when treated orally with 0.014 (low), 0.028 (medium) and 0.042 (high) mg/kg daily for a period of 90 days. Repeated administration of RPR-II caused significant increase of ASAT and ALAT enzymes in serum, liver and kidney and significant decrease was recorded in lung in both male and female rats when measured after 45 and 90 days of treatment. This compound also caused significant inhibition of RBC AChE indicating its effect on nerve synapsis. Females were more susceptible than males with regard to ASAT and ALAT levels in serum and liver and also in kidney ASAT, whereas reverse trend was recorded in lung ALAT, suggesting sexual dimorphism in the treated rats. These studies also indicated that the levels of these affected enzymes were recovered to normal conditions after 28 days of post treatment (withdrawal study). Positive correlation was observed with regard to these enzymes between serum, liver and kidney, whereas in case of serum and lung a negative correlation was recorded. These enzymes profile elucidates lung necrosis whereas in other tissues the level of enzymes increased showing an adaptive mechanism due to the chemical stress.     

大鼠IgA肾病模型的建立及血清中IL-6、FN、NO的检测

目的建立大鼠IgA肾病（IgAN）模型,测定大鼠血清中的白介素-6（IL-6）、纤维结合蛋白（FN）、一氧化氮（NO）,探讨这些指标水平的变化与IgAN免疫损伤的相关性,为临床治疗提供动物实验研究依据。方法24只大鼠被随机分成3组,每组8只。模型组和治疗组用免疫复合物法复制;正常对照组用生理盐水。10周后,治疗组大鼠被给予雷公藤多甙片3周。留取所有大鼠血清测定IL-6、FN、NO;留取所有大鼠尿液测定红细胞（RBC）、总蛋白量（TPR）;留取所有大鼠肾组织作病理学检查。结果模型组中大鼠尿液中RBC、TPR含量较治疗组及正常对照组显著增高（P〈0．01）;血清中的IL-6、FN的水平较治疗组及正常对照组显著增高（P〈0．01）;血清中的NO水平较治疗组及正常对照组显著降低（P〈0．01）。治疗组的大鼠肾组织病理损伤程度较模型组明显减轻（P〈0．01）。结论血清中的IL-6、FN及NO的水平与RBC数、TPR及肾组织病理损伤程度相关,它们可作为观察IgAN治疗效果的重要指标,也可作为IgAN严重性的预测指标。下调血中的IL-6、FN及上调NO的水平,可减少IgA与FN免疫复合物的形成,从而改善肾组织的免疫损伤。     

Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls

Previous data from our and other labs demonstrated a decreased chiro-inositol content in urine and tissues of human subjects and animals with type 2 diabetes. In urine this decrease in chiro-inositol was accompanied by an increase in myo-inositol content. Decreased urine levels of chiro-inositol in monkeys were next correlated with the severity of underlying insulin resistance determined by five separate assays. To investigate the decreased chiro-inositol and the accompanying increased myo-inositol excretions in urine in humans and monkeys, we postulated a defect in the epimerization of myo-inositol to chiro-inositol. [(3)H]Myo-inositol was then shown to be converted to [(3)H]chiro-inositol in rats in vivo and in fibroblasts in vitro in a process stimulated by insulin. We next demonstrated that the conversion of [(3)H]myo-inositol to [(3)H]chiro-inositol in vivo was markedly decreased in GK type 2 diabetic rats compared to Wistar controls in liver, muscle, and fat, insulin sensitive tissues. Decreases of 20-25% conversion to baseline levels of under 5% conversion were observed. In the present work, we initially compared the total contents of myo-inositol and chiro-inositol in GK type 2 diabetic rat kidney, liver, and muscle compared to Wistar controls. We demonstrated a consistent decreased total chiro-inositol to myo-inositol ratio in kidney, liver, and muscle compared to controls. We next established the presence of a myo-inositol to chiro-inositol epimerase activity in rat liver cytosol. Enzyme activity was shown to be time and enzyme concentration dependent with a broad pH optimum. It required NADH and NADPH for full activity, which is compatible with its action via an oxido-reductive mechanism. Lastly, we demonstrated that the epimerase enzyme bioactivity was significantly decreased in muscle, liver, and fat cytosolic extracts of GK type 2 diabetic rats versus Wistar controls. Decreased myo-inositol to chiro-inositol epimerase activity may therefore play a role in explaining the decreased chiro-inositol to myo-inositol urine and tissue ratios observed here and in previous animal and human studies. Further it may also possibly play a role in the underlying insulin resistance.     

Preventive effect of 20(S)-ginsenoside Rg3 against lipopolysaccharide-induced hepatic and renal injury in rats

The preventive effect of 20(S)-ginsenoside Rg₃ (20(S)-Rg₃) on lipopolysaccharide (LPS)-induced oxidative tissue injury in rats was investigated in this study. The elevated serum nitrite/nitrate, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and creatinine levels in LPS-treated control rats were significantly decreased following 15 consecutive days of 20(S)-Rg₃ administration. In addition, thiobarbituric acid-reactive substance levels in the serum, liver and kidney were dose-dependently lower in 20(S)-Rg₃-treated groups than in the LPS-treated control group. The nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) protein expressions in the liver and kidney were significantly increased by LPS treatment. However, the 20(S)-Rg₃ administrations significantly decreased these protein expressions except for HO-1 in the liver. On the other hand, in the kidney, oral administration of 20(S)-Rg₃ showed a tendency to reduce NF-κB and iNOS protein expressions and also significantly reduced the elevated COX-2 and HO-1 protein expressions at a dose of 10 mg/kg body weight/day. All these results suggest the preventive effect of 20(S)-Rg₃ against LPS-induced acute oxidative damage in the liver and kidney and the preventive effect of 20(S)-Rg₃ administration against LPS toxicity was thought to be more predominant in the liver than kidney.     

Effects of serpasil on lipids,lipoprotein lipase and lipogenic enzymes in alloxan diabetic rats

Diabetes intensifies the development of atherosclerosis. Treatment with antihypertensive drug, serpasil, arrested the progression of atherosclerosis in alloxan diabetic rats by significantly decreasing the concentration of cholesterol, phospholipids and triglycerides of serum, liver, kidney and aorta. Serpasil also decreased fasting blood sugar and urine sugar levels in these rats. Serpasil administration remarkably altered the deranged lipid metabolism in alloxan diabetic rats by nearly restoring the lipolytic and lipogenic enzyme activity to that of the normal