白藜芦醇对高脂饲养小鼠脂肪组织氧化还原状态及血脂的影响

本研究旨在探索白藜芦醇(RSV)对不同程度肥胖小鼠脂肪氧化应激状态和血脂的影响。高脂日粮(HFD)处理12周的昆明小鼠分为3类:肥胖抵抗(DIO-R)、中体重(Med)和肥胖(DIO),分别饲喂HFD、HFD+0.3 g/kg RSV和HFD+0.6 g/kg RSV日粮18周,并以正常日粮小鼠为对照。结果表明,0.6 g/kg RSV处理可显著降低DIO小鼠体重、腹脂率,显著提高脂肪组织抗氧化能力,改善血脂。0.3 g/kg RSV处理对DIO-R小鼠也有类似趋势,但0.6 g/kg RSV处理引起DIO-R小鼠脂肪组织抗氧化能力下降、血脂紊乱。总之,RSV在不同程度肥胖小鼠具有剂量特异性的氧化应激调控作用。     

特异性卵黄抗体(IgY)对小鼠大肠杆菌败血症的保护作用

目的:研究特异性IgY对小鼠大肠杆菌败血症的保护作用.方法:以灭活的E.coli O111免疫产蛋母鸡,抗体经水稀释及盐析分离纯化.ELISA法检测大肠杆菌特异性IgY对大肠杆菌及LPS的结合活性.腹腔注射E.coli O111(1011cfu/mL)建立小鼠败血症模型,攻毒剂量为0.1mL/10g体重.小鼠随机分为5组,分别给药保护:空白组(生理盐水)、阴性对照组(非特异性IgY,20mg/mL)、阳性对照组(头孢哌酮20mg/mL)、高剂量组(特异性IgY,40mg/mL),低剂量组(特异性IgY,20mg/mL).给药剂量为:攻毒前,0.15mL/10g体重,每天一次,共两天;攻毒后,0.25mL/10g体重,每天一次,共七天.观察小鼠临床表现、体重变化、白细胞(WBC)和血小板(PLT)数变化及各组小鼠的死亡率.结果:特异性IgY与E.coli O111和LPS均有体外结合活性.大肠杆菌攻毒后,小鼠体重下降,各组小鼠外周血中WBC和PLT数均有不同程度的下降.特异性IgY保护组各项指标较快恢复到正常水平,其他组恢复缓慢.各组小鼠七天内的死亡率分别为:空白组与阴性对照组都为100%;阳性对照组60%;低剂量IgY组30%;高剂量IgY组10%.结论:特异性IgY对小鼠大肠杆菌败血症有保护作用.     

特异性卵黄抗体(IgY)对小鼠内毒素血症的保护作用

目的:研究特异性卵黄抗体(Egg yolk immunoglobulin,IgY)对小鼠内毒素血症的保护作用.方法:以灭活的E.coli O111免疫产蛋母鸡制备特异性IgY抗体.ELISA法检测对E-coli O111及内毒素(Lipopolysaecharide,LPS)的结合活性.腹腔注射LPS(2mg/m1),0.1 ml/10g体重,建立小鼠内毒素血症模型.小鼠随机分为5组,分别给药保护:空白组(生理盐水)、阴性对照组(非特异性IgY,20mg/ml)、阳性对照组(头孢哌酮钠,20mg/ml)、高剂量组(特异性IgY,40mg/m1),低剂量组(特异性IgY,20mg/ml).给药剂量为:攻毒前,0.15 ml/l0 g体重,24 h一次,共两次;攻毒后,0.25 ml/10 g体重,24 h一次,共7次.观察小鼠一般情况,体重变化,外周血中白细胞(WBC)和血小板(PLT)数的变化及各组小鼠的死亡率.结果:特异性IgY与E.coli O111及LPS均有体外结合活性.LPS感染后,各组小鼠外周血中WBC和PLl均有不同程度的下降,体重下降.特异性抗体保护组各指标较快恢复到正常水平,其他组恢复缓慢.各组小鼠七天内死亡率分别为:空白组,100%;阴性对照组,85%;阳性对照组,30%;低济量组,30%;高剂量组,0%.结论:特异性IgY对内毒素血症小鼠有保护作用.     

小麦胚芽油维生素E软胶囊抗氧化功效研究

目的:研究小麦胚芽油维生素E软胶囊抗氧化作用。方法:根据《保健食品检验与评价技术规范》,以0.083 g/kg.bw、0.167 g/kg.bw、0.500g/kg.bw剂量的小麦胚芽油维生素E软胶囊给小鼠灌胃30天,结果显示0.500 g/kg.bw剂量能显著降低血中脂质过氧化物(MDA)水平(P0.05),显著提高血清超氧化物歧化酶(SOD)活力(P0.05),显著提高血中GSH含量(P0.05),各剂量组血清蛋白质羰基与对照组比较无显著性差异(P0.05)。结论:小麦胚芽油维生素E软胶囊对动物具有抗氧化功效。     

鱼皮胶原蛋白肽复方制品对小鼠免疫功能的影响

本试验旨在研究鱼皮胶原蛋白肽与壳寡糖、人参提取物、黄芪提取物、当归提取物的药物组合物(鱼皮胶原蛋白肽复方制品)对免疫功能的影响。将336只SPF级健康ICR雌性小鼠随机分为四批(N=84),分别进行细胞免疫功能、脏器/体重比值及体液免疫功能、单核-巨噬细胞功能及NK细胞活性检测。每批随机分为7组(n=12),阴性对照组、高(3.0 g/kg)、中(1.0 g/kg)、低(0.5 g/kg)剂量复方制品组和鱼皮胶原蛋白肽组,连续灌胃30天后,测定各项功能指标。结果发现,与阴性对照组相比,各剂量组小鼠的迟发变态反应、脏器/体重比值、抗体生成细胞数无显著差异(P0.05);复方制品各剂量组小鼠的淋巴细胞增殖能力、血清溶血素水平以及单核-巨噬细胞碳廓清吞噬指数明显增强,且效果优于鱼皮胶原蛋白肽组。由此得出,鱼皮胶原蛋白肽复方制品具有较好的增强小鼠免疫力的作用。     

芦笋对高脂饮食小鼠体质量的影响

目的探究芦笋对高脂饮食小鼠体质量的影响。方法将实验动物随机分为正常组、高脂饮食组、高脂饮食低剂量芦笋组、高脂饮食中剂量芦笋组、高脂饮食高剂量芦笋组、高脂饮食阳性对照组。其中正常组喂食正常饲料,其余组喂食高脂饲料。分别灌胃蒸馏水(正常组、高脂饮食组)、芦笋1.05g/(kg·d)(高脂饮食低剂量芦笋组)、芦笋2.10g/(kg·d)(高脂饮食中剂量芦笋组)、芦笋4.20g/(kg·d)(高脂饮食高剂量芦笋组)、降脂理肝汤1.19g/(kg·d)(高脂饮食阳性对照组),每天2次,每次0.35mL。比较分析各组小鼠的体质量变化,同时对各组之间的雌性小鼠和雄性小鼠体质量变化进行对比。结果随饲养时间的增加,服用芦笋后的三组小鼠体质量均低于高脂饮食组,但与高脂饮食组相比差异无统计学意义(P0.05)。高脂饮食低剂量芦笋组、高脂饮食中剂量芦笋组、高脂饮食高剂量芦笋组小鼠的体质量变化率低于高脂饮食组,差异无统计学意义(P0.05)。对各组之间的雌性小鼠和雄性小鼠体质量变化进行对比可以发现雄性小鼠的体质量变化大于雌性小鼠的,差异有统计学意义(P0.05)。结论芦笋能降低高脂饮食小鼠的体质量,雄性小鼠和雌性小鼠的体质量变化存在差异。     

精氨酸双糖苷对小鼠毒性实验研究

为观察精氨酸双糖苷(AFG)毒性反应,通过高效阳离子柱洗脱纯化AFG,ICR小鼠80只,随机分为4组,每组20只,雌雄各半。各组分别灌胃给予生理盐水,AFG 30 mg/kg、2 g/kg、6 g/kg,每天给药一次,连续给药90 d,并观察各组小鼠的状态。各组给药结束后,眼球取血,处死,解剖检查,取材、制片和H.E染色进行病理学检查。结果显示,AFG 6 g/kg组,连续给药60 d后,个别小鼠出现眼睛红肿,行动缓慢等现象。AFG低、中、高剂量组连续给药90 d后,与空白对照组比较,各剂量组体重变化和食物消耗量无显著性差异,AFG 6 g/kg组肝、脾指数明显降低(P0.01,P0.05);血液生化指标的测定中,AFG 30 mg/kg、2 g/kg组肌酐明显上升(P0.05),AFG 6 g/kg组谷丙转氨酶、谷草转氨酶升高(P0.05),甘油三酯明显升高(P0.01)。其它血液生化指标与空白对照组比较无显著性差异。现有数据表明,90 d内服用AFG对小鼠生理活性和状态无明显毒性作用。     

DS-1226对慢性睡眠干扰所致小鼠抑郁行为的改善作用

目的研究人参皂苷水解产物DS-1226对慢性睡眠干扰小鼠的抗抑郁作用,为抗抑郁药物的研发提供科学依据。方法将72只雄性ICR小鼠分为空白对照组、模型组、阳性对照组(盐酸帕罗西汀,10 mg/kg)、DS-1226低剂量组(20 mg/kg)、中剂量组(40 mg/kg)、高剂量组(80 mg/kg)。除空白组外,其他组小鼠先进行3 d的滚筒适应,然后连续进行14 d睡眠干扰。采用体重监测、自主活动实验、悬尾实验、强迫游泳实验等实验方法,评价DS-1226的抗抑郁作用。结果连续进行14 d睡眠干扰后,与空白对照组相比,模型组体重显著下降,悬尾和强迫游泳不动时间显著增长。与模型组相比,DS-1226中剂量组显著逆转睡眠干扰所致的体重下降,其他各给药组均未能显著逆转睡眠干扰所致的体重下降;阳性药组的悬尾不动时间极显著减少,强迫游泳不动时间有减少趋势;DS-1226中剂量悬尾不动时间显著减少,强迫游泳不动时间有明显减少趋势;DS-1226高剂量组悬尾和强迫游泳不动时间均显著减少。结论 DS-1226具有改善慢性睡眠干扰小鼠抑郁样行为的作用。     

芪胶升白胶囊联合环磷酰胺对S_(180)荷瘤小鼠增效减毒作用研究

本文探讨芪胶升白胶囊(QSC)与环磷酰胺(CTX)联合应用对S_(180)荷瘤小鼠的增效减毒作用。造荷S_(180)肿瘤小鼠模型,60只荷瘤小鼠随机分为5组:模型组,CTX(30 mg/kg)组,CTX+QSC低、中、高剂量(0.5、1.0、2.0 g/kg)组。每日测量小鼠体重和肿瘤体积,分别连续给药15 d后,测小鼠血细胞计数,脏器指数和抑瘤率,HE染色法观察肿瘤组织形态,Annexin V/PI双染流式术测定肿瘤组织细胞的凋亡率。实验结果显示与CTX组比较,联合用药各剂量组的小鼠肿瘤体积均较小,抑瘤率以及肿瘤细胞凋亡率均有提高,胸腺、脾脏指数也较高,联合用药高剂量组白细胞计数增高统计学意义显著(P0.01),镜下观察肿瘤组织坏死明显,表明QSC与CTX联合使用对S_(180)荷瘤小鼠有一定的增效减毒作用。     

天麻改善小鼠睡眠作用研究

目的:探讨天麻粉对小鼠改善睡眠作用的影响。方法:144只雌性KM小鼠随机分为三个实验组,每个实验组48只,分别设置低、中、高三个剂量组,分别给予0.4、0.8、1.2 g/kg BW天麻粉,同时设置阴性对照组(给予等量蒸馏水),各组均为12只(n=12)。给予小鼠连续灌胃30天后开始实验。实验一组进行直接睡眠实验和戊巴比妥钠阈下剂量催眠实验,实验二组进行巴比妥钠睡眠潜伏期实验,实验三组进行延长戊巴比妥钠睡眠时间实验。结果:与阴性对照组比较,天麻粉各剂量组小鼠终重均没有明显改变(p0.05);高剂量组提高阈下剂量戊巴比妥钠诱导的小鼠睡眠发生率作用,差异有统计学意义(p0.05);中、高剂量组明显缩短巴比妥钠睡眠潜伏期时间,差异有显著性统计学意义(p0.01);高剂量组明显延长戊巴比妥钠诱导小鼠睡眠时间的作用,差异有显著统计学意义(p0.01)。结论:天麻粉对小鼠具有一定的改善睡眠作用,且对小鼠体重增长无影响。     

蝉棒束孢子实体的致畸性评价及对高血糖小鼠血糖的影响

对妊娠第7-16天Wistar大鼠连续给予口服蝉棒束孢子实体低、中、高3个剂量（0.85、1.70、3.40g/kg）10d,观察给药组对大鼠孕期体重、死胎率、吸收胎率、活胎数、每窝平均胎仔数、胎鼠重、胎鼠身长、前囟宽度、子宫连胎重及胎鼠外观、内脏发育、骨骼发育的影响,研究妊娠动物接触蝉棒束孢子实体后引起的致畸可能性。对正常小鼠、STZ致高血糖模型小鼠给予口服不同剂量的人工培植蝉棒束孢子实体（0.4、0.25、0.125g/kg）,测定空腹血糖及糖耐量,评价蝉棒束孢子实体的降血糖作用。结果表明：与阴性对照组相比,人工培植蝉棒束孢子实体各剂量组在大鼠孕期体重、死胎率、吸收胎率、胎鼠重、胎鼠身长和前囟宽度、胎鼠外观、内脏和骨骼发育等方面均无显著性差异（P>0.05）;与模型对照组（0g/kg BW）相比,人工培植蝉棒束孢子实体中、低两个剂量组均能降低STZ致高血糖模型小鼠给葡萄糖后0.5h血糖水平（P<0.05）,低剂量组能明显降低高血糖模型小鼠0-2h血糖曲线下面积,且对小鼠体重及正常小鼠空腹血糖均无不良影响。提示人工培植蝉棒束孢子实体对大鼠无明显的母体毒性、胚胎毒性和致畸性;对高血糖小鼠具有降血糖的作用。     

Modification of cyclophosphamide-induced clastogenesis and apoptosis in rats by alpha-lipoic acid

The aim of the present study was to investigate the protective efficacy of alpha-lipoic acid (LA) on the cyclophosphamide (CP)-induced chromosomal aberrations (CA) and apoptosis in the bone marrow of rats. Male Wistar rats of 140+/-20 g were categorized into eight groups. Five groups were administered CP (40 mg/kg body weight, intraperitoneally) to induce toxicity; four of these groups received a single intraperitoneal injection of LA at a dose of either 100 or 200 mg/kg body weight, and either 30 or 60 min prior to CP administration. A vehicle-treated control group and LA control groups were also included. Twenty-four hours after CP treatment, the frequency of CA in bone marrow cells were significantly increased in comparison with the controls. The CP-induced CA were associated with significant increase in DNA damage in the bone marrow as evidenced by increased single strand breaks, whereas in rats treated with LA and CP, the frequency of CA and single strand breaks were significantly decreased in comparison to those given CP alone. CP administration distinctly triggered the apoptotic and necrotic cell death, and LA pretreatment affected cell death by decreasing the number of apoptotic and necrotic cells. The protective effect of LA was found to be stronger at a dose of 200 mg/kg body weight than 100 mg/kg body weight dosage, indicating the dose dependent protective effect of LA. However, the protection by LA was not dependent on the time intervals between LA and CP administration. The results of this study illustrate the protective effect of LA on the CA and apoptosis induced by CP in the erythropoietic system of rats.     

饲料中棕榈油替代鱼油和豆油对黄颡鱼生长和肌肉脂肪酸组成的影响

为研究不同棕榈油替代水平对黄颡鱼生长性能、肌肉脂肪酸组成、形体指标和肝脏组织结构的影响, 实验采用5组等氮(400 g/kg)等脂(100 g/kg)等能(15.70 MJ/kg)饲料饲喂黄颡鱼[(16.15±0.04) g], 对照饲料以鱼油鲶豆油1鲶2混合为脂肪源, 实验饲料以棕榈油分别替代10、25、40和55 g/kg的混合脂肪源。经过8周的养殖实验, 结果表明棕榈油替代水平对黄颡鱼的摄食量、终末体重、特定生长率、饲料效率和蛋白沉积率未产生显著性的影响(P>0.05), 但是上述指标均呈现先升高后略微下降的趋势, 并在25 g/kg替代组达到最大值。背肌肌肉中亚油酸和n-3HUFA含量随着棕榈油替代水平的上升而显著下降(P<0.05), 但n-3/n-6比值随着棕榈油替代水平的上升而显著上升(P<0.05), 棕榈油替代水平对各组黄颡鱼的肥满度和脏体比未产生显著性的影响(P>0.05), 但是55 g/kg棕榈油替代水平组肝体比显著高于25 g/kg棕榈油添加组(P<0.05), 且55 g/kg棕榈油替代水平组黄颡鱼的肝脏组织出现细胞肿胀, 细胞核移位, 肝血窦和脂肪细胞数量明显增多等不良影响。据上所述: 对于黄颡鱼幼鱼, 棕榈油可以替代25 g/kg的混合脂肪源(鱼油鲶豆油=1鲶2)不影响鱼体生长性能并且在一定程度上改善了背肌肌肉脂肪酸组成。     

Oxidative renal injury and lipoprotein oxidation in hypercholesterolemic atherogenesis: Role of eicosapentaenoate-lipoate (EPA-LA) derivative

Hypercholesterolemia, an independent risk factor for increased oxidative renal injury, is associated with the formation of oxidized low-density lipoprotein. Production of reactive oxygen species and nitrogen species have been implicated in diet-induced hypercholesterolemia, principally as means of oxidising low-density lipoproteins. This in turn initiates the accumulation of cholesterol in macrophages, which sets key event in the initiation of atherosclerosis. The aim of the present work is to evaluate the effects of eicosapentaenoic acid (EPA), DL alpha-lipoic acid (LA) and eicosapentaenoate-lipoate derivative (EPA-LA) in controlling the atherogenic disturbances. Four groups of male Wistar rats were fed with a high cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. Among them, 3 groups of rats were treated with either EPA (35 mg/kg body weight/day, oral gavage), LA (20 mg/kg body weight/day, oral gavage) or EPA-LA derivative (50 mg/kg body weight/day, oral gavage) from 16th day to 30th day of the experimental period. Abnormal increase in the levels of reactive oxygen species, 3-nitrotyrosine, malondialdehyde and protein carbonyl as well as an elevation in the activities of xanthine oxidase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase was observed in renal tissue of HCD fed rats. HCD fed rats also showed an increased susceptibility of the apo B-containing lipoproteins to in vitro oxidation. These changes were restored partially in the EPA and LA administered groups. However, the combined derivative EPA-LA almost ameliorated the hypercholesterolemic-oxidative changes in the HCD fed rats.     

Differential effect of polyherbal,antiobesity preparation,OB-200G in male and female mice and monosodium glutamate-treated rats

Effect of administration of different doses (0.25, 0.5, 1 and 2 g/kg, twice daily, po) of a polyherbal preparation, OB-200G and fluoxetine (10 mg/kg, ip) for 21 days was studied on food intake and body weight in male and female Laka mice. The study further investigated the effect of administration of 0.5 g/kg dose of OB-200G for 40 days on body weight, fat pad weights, locomotor activity and biochemical parameters in monosodium glutamate (MSG)-treated male and female Wistar rat pups. Administration of OB-200G produced dose dependent decrease in body weight in both male and female mice. On the other hand, fluoxetine decreased body weight only in female mice. The food intake was significantly (P < 0.05) increased in both fasted male and female mice after treatment with the lower dose (0.25 g/kg, po) of OB-200G. However, significant (P < 0.05) decrease in food intake was recorded with the administration of higher doses (0.5, 1 and 2 g/kg, po) of OB-200G and fluoxetine in fasted female mice on day 1, 7, 14 and 21. But in male mice differential effect on food intake was recorded at different doses on day 1, 7, 14 and 21. Further, OB-200G administration significantly (P < 0.05) decreased body weight and fat pad weights, increased serum glucose levels and ambulatory activity in MSG-treated female rats but not in MSG-treated male rats. The results suggest that OB-200G involves gender differences in mediating its antiobesity effect and may supplement the current armamentarium for the treatment of obesity.     

Effect of ethanol on the levels of dopamine and its metabolites in the brain of rats with different degree of sensitivity to stress

It was shown, that content of dopamine and its metabolites (DOPAC and HVA) are the same in two groups of rats with different time of immobilization in forced swimming test. One group of low active (LA) animals experienced the immobilization more than 300s, other high active (HA) rats for less than 120 s. Ethanol (2 g/kg per oris) increased the level of DA in the striatum and medial prefrontal cortex only in LA rats and besides, the concentration of dopamine after ethanol administration was higher in the n. accumbens of LA rats, than in that of HA rats. The authors suggest that differences in dopamine content between LA and HA rats are connected with different levels of voluntary alcohol consumption. The opportunity to use both groups of HA and LA rats for developing models of pathogenic heterogeneity of alcoholism is discussed.     

Preliminary studies on acute and subacute toxicity of an antidiabetic herbal preparation, Dianex

Dianex, a polyherbal formulation intended to use for diabetic patients, has been screened for toxic effects. For acute toxicity studies, Dianex was administered orally in graded doses of 0.75-10 g/kg to the mice. For subacute toxicity studies, different doses of Dianex (1.0, 1.5 and 2.5 g/kg) were administered orally to the rats once daily for 30 days. Animals were observed for physiological and behavioural responses, mortality, food and water intake and body weight changes. Hematological evaluation was performed weekly. All the animals were sacrificed on 31st day and changes in organ weights and histology were examined. Biochemical studies were done in liver and serum. No mortality was observed up to 10 g/kg of Dianex in acute toxicity study. Daily administration of as high as 2.5 g/kg dose of Dianex did not result in any mortality or changes in gross behaviour, body weight, weight and histology of different organs or serum and liver biochemistry. However, significant increase in RBC count and hemoglobin level was observed in the treated animals at all doses. Other peripheral blood constituents were in the normal range. The dose of Dianex to produce significant antidiabetic activity in mouse, 0.25-0.5 g/kg, is much lower than the doses used in the present study. Therefore such doses may be safe for daily administration without causing any serious side effects.     

Effect of α-Lipoic Acid on Lipid Profile in Rats Fed a High-Fructose Diet

This study investigated the effect of administration of α-lipoic acid (LA) on lipid metabolism in high fructose–fed insulin-resistant rats. High-fructose feeding (60 g/100 g diet) to normal rats resulted in a significant increase in the concentrations of cholesterol, triglycerides (TGs), free fatty acids (FFAs), and phospholipids in plasma, liver, kidney, and skeletal muscle. Reduced activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) and increased activity of the lipogenic enzyme hydroxymethylglutaryl–coenzyme A (HMG-CoA) reductase were observed in plasma and liver. High-density lipoprotein cholesterol (HDL-C) was significantly lowered and very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated. Treatment with LA (35 mg/kg body weight intraperitoneal) reduced the effects of fructose. The rats showed near-normal levels of lipid components on plasma and tissues. Activities of key enzymes of lipid metabolism were also restored to normal values. Cholesterol distribution in the plasma lipoproteins was normalized, resulting in a favorable lipid profile. This study demonstrates that LA can alter lipid metabolism in fructose-fed insulin-resistant rats and may have implications in the treatment of insulin resistance.     

Temporal Variations in Transcutaneous Passage of Drugs: The Example of Lidocaine in Children and in Rats

Because a eutectic mixture of lidocaine and procaine (EMLA cream) is used to treat pain in children who are undergoing venipuncture for screening clinical presurgery laboratory tests, this study was designed to investigate the influence of the time of application of EMLA cream on lidocaine transcutaneous absorption in children. The same phenomenon was also studied in rats. Local application of EMLA (right and left cubital fossae) was performed 1 hour before venipuncture in two groups of children (0.5 g/kg body weight at two sites), at 08:15 or 16.15 h; blood samples were performed 1 h later. Two groups of five rats each received 12 mg/kg lidocaine at 07:30 or 19.30 h by application to the back skin. Blood samples were collected 0.5, 1, 1.5, 2, 3, and 4 h after application. Plasma lidocaine levels were assayed according to an immunoenzymatic method (Abbott). Our data indicate that the lidocaine plasma levels were significantly different: higher in the evening for the children or in the morning for the rats. The plasma level of the local anesthetics (LA) represents an elimination route and thus may be inversely correlated to the skin amount of the LA.     

Fructose Diet-Induced Skin Collagen Abnormalities Are Prevented by Lipoic Acid

Nonenzymatic glycation of proteins, leading to chemical modification and cross-linking are of importance in the pathology of diabetic complications.We studied the effect of α-lipoic acid (LA) on the content and characteristics of the protein collagen from skin of high-fructose fed rats. The rats were divided into 4 groups of 6 each. Two groups of rats were fed with a high fructose diet (60 g/100 g diet) and administered either LA (35 mg/kg b.w., i.p) (FRU+LA) or 0.2 ml vehicle (saline) (FRU) for 45 days. The other 2 groups were fed with control diet containing starch (60 g/100 g diet) and administered either saline (CON) or lipoic acid (CON+LA). The rats were maintained for 45 days and then sacrificed. Plasma glucose, insulin, fructosamine, protein glycation, and blood glycated hemoglobin (HbA₁C) were measured. Collagen was isolated from skin and the physicochemical properties of collagen were studied. Fructose administration caused accumulation of collagen in skin. Extensive cross-linking was evidenced by enhanced glycation and AGE-linked fluorescence. Increased peroxidation and changes in physicochemical properties such as shrinkage temperature, aldehyde content, solubililty pattern, susceptibility to denaturing agents were observed in fructose-fed rats. SDS gel pattern of collagen from these rats showed elevated β component of type I collagen. These changes were alleviated by the simultaneous administration of LA. Administration of LA to fructose-fed rats had a positive influence on both quantitative and qualitative properties of collagen. The results suggest a mechanism for the ability of LA to delay diabetic complications.