Lactoferrin Prevents Hepatic Injury and Fibrosis via the Inhibition of NF-κB Signaling in a Rat Non-Alcoholic Steatohepatitis Model

Non-alcoholic steatohepatitis (NASH) can cause liver cirrhosis and hepatocellular carcinoma (HCC), with cases increasing worldwide. To reduce the incidence of liver cirrhosis and HCC, NASH is targeted for the development of treatments, along with viral hepatitis and alcoholic hepatitis. Lactoferrin (LF) has antioxidant, anti-cancer, and anti-inflammatory activities. However, whether LF affects NASH and fibrosis remains unelucidated. We aimed to clarify the chemopreventive effect of LF on NASH progression. We used a NASH model with metabolic syndrome established using connexin 32 (Cx32) dominant negative transgenic (Cx32ΔTg) rats. Cx32ΔTg rats (7 weeks old) were fed a high-fat diet and intraperitoneally injected with dimethylnitrosamine (DMN). Rats were divided into three groups for LF treatment at 0, 100, or 500 mg/kg/day for 17 weeks. Lactoferrin significantly protected steatosis and lobular inflammation in Cx32ΔTg rat livers and attenuated bridging fibrosis or liver cirrhosis induced by DMN. By quantitative RT–PCR, LF significantly down-regulated inflammatory (Tnf-α, Il-6, Il-18, and Il-1β) and fibrosis-related (Tgf-β1, Timp2, and Col1a1) cytokine mRNAs. Phosphorylated nuclear factor (NF)-κB protein decreased in response to LF, while phosphorylated JNK protein was unaffected. These results indicate that LF might act as a chemopreventive agent to prevent hepatic injury, inflammation, and fibrosis in NASH via NF-κB inactivation.     

Supplementation with branched-chain amino acids attenuates hepatic apoptosis in rats with chronic liver disease

Branched-chain amino acids (BCAA) can function as pharmacologic nutrients for patients with decompensated cirrhosis. However, the effects of BCAA at the early stage of chronic liver disease are not clear. We hypothesized that early BCAA supplementation would attenuate the progression of chronic liver disease. The present study examined the effects of BCAA supplementation on the progression of chronic liver disease in rats caused by injected carbon tetrachloride (CCl₄). Sprague-Dawley rats were fed with a casein diet (control group) or the same diet supplemented with BCAA (BCAA group) for 11 weeks, and all rats were repeatedly injected with CCl₄. Food intake did not significantly differ between control and BCAA groups during the experimental period. Plasma alanine aminotransferase activities gradually increased during the experimental period in both groups but peaked later in the BCAA group. Liver fibrosis was more evident in the control group. Levels of connective tissue growth factor messenger RNA were significantly lower in the livers of rats in the BCAA group than in the control group. Terminal deoxynucleotidyl transferase–mediated deoxyuridine 5-triphosphate nick end labeling assays found considerably more hepatic apoptosis in the control group. Liver cytosolic cytochrome c levels and expression of the proapoptotic Bax protein in the mitochondrial fraction were significantly lower in the BCAA group than in the control group. These results suggest that supplementation with BCAA delays the progression of chronic liver disease caused by CCl₄ in rats by attenuating hepatic apoptosis.     

Vitamin A supplementation modifies the antioxidant system in rats

BACKGROUND/OBJECTIVESIt has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats.MATERIALS/METHODSForty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope.RESULTSLipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation.CONCLUSIONSThese results indicate that appropriate supplementation of vitamin A might have a beneficial effect on the antioxidant system in rats.     

缬沙坦抗大鼠肝纤维化的实验研究

目的观察缬沙坦预防、治疗大鼠肝纤维化的作用和机制。方法雄性SD大鼠30只,随机分为3组：缬沙坦预防组（A组）,模型组（B组）,缬沙坦治疗组（C组）。二甲基亚硝胺（DMN）腹腔注射,各组每周连续3d,1;L／d,共4周。A组造模同时给于缬沙坦10mg／（kg·d）灌胃,共4周,第5周起停止腹腔注射DMN后仍按原剂量灌胃,再4周。C和B2组停止造模后,分别给予缬沙坦10mg／（kg·d）或生理盐水灌胃,共4周。8周后留取肝标本,行HE染色和Masson染色,以免疫组化法检测a-平滑肌肌动蛋白（a—SMA）含量。结果（1）A组：肝索排列基本整齐,有少量出血,汇管区稍扩大,未见胶原纤维增生。B组：肝组织大片出血坏死,有假小叶形成。c组：肝索排列紊乱,有出血坏死,汇管区扩大,有纤维间隔伸向肝小叶。（2）Masson染色胶原定量分析：B组明显高于A、C2组（P〈0．01）,A组低于C组（P〈0．05）。（3）肝窦壁a—SMA观察：c组肝窦壁强阳性表达,A组肝窦壁基本不表达,仅见于汇管区,B组肝窦壁阳性表达,3组定量差异有统计学意义（P〈0．05）。结论在DMN诱导的肝纤维化模型中,缬沙坦部分通过抑制肝星状细胞（HSC）的活化预防和治疗肝纤维化,且预防效果优于治疗。     

Pantothenic acid refeeding diminishes the liver,perinephrical fats,and plasma fats accumulated by pantothenic acid deficiency and/or ethanol consumption

ObjectivePantothenic acid (PaA) is a vitamin that is an integral part of coenzyme A (CoA). CoA is an essential coenzyme in fat metabolism. The aim of this study was to determine whether PaA deficiency causes the accumulation of tissue fats and, if so, can refeeding of PaA decrease such accumulated fat.MethodsWeaning rats were fed the PaA-free diet for 30 d. Rats were then divided into two groups. One group was continuously fed the PaA-free diet, and the other was fed the PaA-containing diet for an additional 13 d. At the end of the experiment, liver fat and perinephric fat were weighed, and plasma triglyceride levels measured. An additional similar experiment was conducted in which rats consumed 15% ethanol instead of water.ResultsFat that accumulated by consuming the PaA-free diet for 30 d was decreased by consuming the PaA-containing diet for an additional 13 d. Ethanol feeding elicited much greater accumulation of liver, perinephric, and plasma fats if rats were fed the PaA-free diet. In such cases, administration of PaA could decrease the accumulated fat.ConclusionPaA deficiency causes fat accumulation, and readministration of PaA decreases the tissue fat in rats fed the pantothenic acid–free diet. Ethanol accelerated the accumulation of fat in rats fed the PaA-free diet. PaA could be beneficial for decreasing accumulated tissue fat.     

Coffee consumption prevents fibrosis in a rat model that mimics secondary biliary cirrhosis in humans

Investigations demonstrated that oxidative stress plays an important role in injury promotion in cholestatic liver disease. We hypothesized that coffee attenuates cholestasis-induced hepatic necrosis and fibrosis via its antioxidant, anti-inflammatory, and antifibrotic properties. The major aim of this study was to evaluate the hepatoprotective properties of coffee and caffeine in a model of chronic bile duct ligation (BDL) in male Wistar rats. Liver injury was induced by 28-day BDL, and conventional coffee, decaffeinated coffee, or caffeine was administered daily. After treatment, the hepatic oxidative status was estimated by measuring lipid peroxidation, the reduced to oxidized glutathione ratio, and glutathione peroxidase. Fibrosis was assessed by measuring the liver hydroxyproline content. The transforming growth factor-β, connective tissue growth factor, α-smooth muscle actin, collagen 1, and interleukin-10 proteins and mRNAs were measured by Western blot and polymerase chain reaction, respectively. Conventional coffee suppressed most of the changes produced by BDL; however, caffeine showed better antifibrotic effects. Coffee demonstrated antioxidant properties by restoring the redox equilibrium, and it also prevented the elevation of liver enzymes as well as hepatic glycogen depletion. Interestingly, coffee and caffeine administration prevented collagen increases. Western blot assays showed decreased expression levels of transforming growth factor-β, connective tissue growth factor, α-smooth muscle actin, and collagen 1 in the coffee- and caffeine-treated BDL groups. Similarly, coffee decreased the mRNA levels of these proteins. We conclude that coffee prevents liver cirrhosis induced by BDL by attenuating the oxidant processes, blocking hepatic stellate cell activation, and downregulating the main profibrotic molecules involved in extracellular matrix deposition.     

Lipid peroxidation and glutathione peroxidase activity in the liver of cholesterol-fed rats.

The effects of cholesterol feeding on lipid peroxidation and on glutathione peroxidase activity in the liver of rats were examined. Cholesterol (1 or 1.5%) was added to two basal diets containing either 10% soy oil (diet 1) or 15% soy oil plus 100 IU of alpha-tocopherol/kg of diet (diet 2). The rate of lipid peroxidation in the liver was determined in vitro by the thiobarbituric acid test and by conjugated diene measurement (234 nm). Cholesterol feeding elevated the rate of lipid peroxidation in the liver of rats fed diet 1 or 2. The rate of lipid peroxidation in rats fed diet 2 increased with duration of feeding suggesting an increased need for antioxidant as the levels of cholesterol or other lipids in the liver elevated. Cholesterol feeding also decreased the activity of liver glutathione peroxidase and pentose phosphate pathway dehydrogenases. Glutathione peroxidase activities increased with the duration of feeding in rats fed basal diet 2, but they remained unchanged in rats fed the same diet supplemented with cholesterol. The study suggests that cholesterol feeding in rats can increase the susceptibility of the tissue to lipid peroxidation and also can lead to a depression in the activity of glutathione peroxidase.     

Freeze-dried instant coffee can promote the activities of antioxidant enzymes and induce weight loss but also aggravate the plasma cholesterol profile in rats

ObjectiveThis study investigated the effect of instant coffee on antioxidant enzyme activity and plasma cholesterol profile during exercise in rats.MethodsForty eight rats were fed a control diet with water (C) or a control diet with a coffee solution (CF). At the end of week 4, animals in each dietary group were subdivided into three exercise groups: before exercise (BE), during exercise (DE), and after exercise (AE). DE groups were exercised on a treadmill for 1 h immediately before being sacrificed. Animals in the AE groups were allowed to take a rest for 1 h after exercise. Antioxidant enzyme activities of the C and CF groups were evaluated with activities of catalase in plasma and superoxide dismutase, the ratio of reduced glutathione to oxidized glutathione, and the level of malondialdehyde in the liver. Plasma concentrations of triacylglycerol, total cholesterol, and high-density lipoprotein cholesterol were also compared.ResultsFinal body weights and food intakes of the CF group were significantly lower than those of the C group. Catalase activities of the CF group were higher than those of the C group BE and AE. Reduced glutathione/oxidized glutathione of the CF group was significantly higher than that of the C group BE and DE. Superoxide dismutase activities of the CF group were higher than those of the C group regardless of exercise. Compared with the C group, there was an increase of total cholesterol and a decrease of high-density lipoprotein cholesterol levels in the CF group. Malondialdehyde levels in the CF group were higher than those in the C group BE and AE.ConclusionIt is suggested that freeze-dried instant coffee can promote activities of antioxidant enzymes and induce weight loss but also aggravate the plasma cholesterol profile in rats.     

Elevated expression of liver gamma-cystathionase is required for the maintenance of lactation in rats

Liver gamma-cystathionase activity increases in rats during lactation; its inhibition due to propargylglycine is followed by a significant decrease in lactation. This is reversible by N-acetylcysteine administration. To study the role of liver gamma-cystathionase and the intertissue flux of glutathione during lactation, we used lactating and virgin rats fed liquid diets. Virgin rats were divided into two groups as follows: one group was fed daily a diet containing the same amount of protein that was consumed the previous day by lactating rats (high protein diet-fed rats); the other virgin group was fed the normal liquid diet (control). The expression and activity of liver gamma-cystathionase were significantly greater in lactating rats and in high protein diet-fed virgin rats compared with control rats. The total glutathione [reduced glutathione (GSH) + oxidized glutathione (GSSG)] released per gram of liver did not differ in lactating rats or in high protein diet-fed rats, but it was significantly higher in these two groups than in control virgin rats. Liver size and the GSH + GSSG released by total liver were significantly higher in lactating rats than in high protein diet-fed virgin rats, and this difference was similar to the amount of glutathione taken up by the mammary gland (454.2 +/- 36.0 nmol/min). The uptake of total glutathione by the lactating mammary gland was much higher than the uptakes of free L-cysteine and L-cystine, which were negligible. These data suggest that the intertissue flux of glutathione is an important mechanism of L-cysteine delivery to the lactating mammary gland, which lacks gamma-cystathionase activity. This emphasizes the physiologic importance of the increased expression and activity of liver gamma-cystathionase during lactation.     

Counteraction of oxidative damage in the rat liver by an ancient grain (Kamut brand khorasan wheat)

ObjectiveWe previously demonstrated in rat plasma the antioxidant protective effect of whole-grain bread, particularly when made from Kamut brand khorasan wheat. In the present study, we investigated the effects of the same experimental breads in rat liver using two different bread-making procedures (baker’s yeast and sourdough fermentation).MethodsRats were examined in the basal condition and after the administration of doxorubicin, a pro-oxidative agent. The following parameters were measured in liver homogenates: glutathione peroxidase and thioredoxin reductase activities, as antioxidant enzymes containing selenium; glutathione, α-tocopherol and β-carotene, as major non-enzymatic cell antioxidants; malondialdehyde and advanced oxidation protein products, as markers of oxidative damage to lipids and proteins, respectively. A histologic evaluation of liver tissue was also conducted.ResultsIn agreement with our previous work, we observed a lower oxidative status and a different activity of glutathione peroxidase and thioredoxin reductase in rats fed the whole-grain Kamut khorasan bread than in rats fed the modern whole-grain durum wheat bread. Histologic evaluation of the hepatic tissue showed the onset of inflammation in response to doxorubicin only in rats fed the modern durum wheat bread.ConclusionOur data confirm that bread made from whole-grain Kamut khorasan protects rats from oxidative stress better than bread made from whole-grain durum wheat. This is consistent with their different antioxidant profiles. The type of wheat used for bread-making appeared to be the main determinant of the observed protective effect.     

Whey protein, as exclusively nitrogen source, controls food intake and promotes glutathione antioxidant protection in Sprague-Dawley rats

The inclusion of whey protein concentrates (WPC) in the diet can lead to a decrease in food intake. Considering that excessive food intake and weight gain are correlated with increased oxidative stress and other risk factors, the anorectic action of WPC may have important clinical implications. The aims of the current study were to verify the effects of WPC in comparison with those of casein on food intake, weight, and oxidized glutathione (GSSG) and total glutathione (GSH) concentrations in the blood and liver with or without oxidative stress induced by oral carbon tetrachloride intoxication. Male Sprague-Dawley rats were fed a balanced liquid diet for 3 weeks. Half of the rats received WPC (group P), while the control group received casein (group C). Group P rats ate significantly less than group C rats (p < 0.0001), and their weights decreased significantly. After carbon tetrachloride intoxication, there was a significant increase in GSH in rats of group P compared with the levels in rats of group C both in the liver (GSH group P 4,994 ± 652.6, group C 2,196 ± 323.2 nmol/mg, p < 0.01) and in the blood (GSH group P 1,368 ± 69.56, group C 1,088 ± 48.35 nmol/ml, p < 0.05). These findings indicate that WPC is effective in reducing food intake and preventing weight gain, and it may also play a protective role against oxidative stress by increasing glutathione synthesis in the liver.     

Beneficial effects of gradual intense exercise in tissues of rats fed with a diet deficient in vitamins and minerals: A pilot study

ObjectiveThis study evaluated the preliminary effects of intense physical training (swimming) on oxidative stress in rats with nutritional deficiencies.MethodsRats were fed with a standard diet or a diet deficient in vitamins and minerals for 4 months. The deficient diet contained one-fourth of the recommended vitamin and mineral levels for rats. From the second month, half of the animals were subjected to a swimming exercise in a plastic container with water maintained at 34 ± 1°C for 1 h/d, five times per week, for 11 wk. The rats were subjected to swimming exercise with loads attached to the dorsal region, which were progressively increased according to their body weight (1% to 7%). Sedentary rats were transported to the experimental room and handled as often in a similar way as the exercise group, except that they were not put in water.ResultsIn the exercised group, blood lactate levels were significantly lower and the heart weight/body weight ratio was significantly higher than in the sedentary group (P < 0.05). Increased lipid peroxidation was observed in the liver, heart, and skeletal muscle of rats fed with the deficient diet, but it was completely reversed by exercise. Exercise also decreased lipid peroxidation levels in the heart and skeletal muscle of rats fed with the standard diet (P < 0.05).ConclusionThis pilot study leads to the continuity of the studies, because the partial results observed suggest that inadequate nutrition may enhance oxidative stress, and that intense chronic physical training may activate antioxidant defenses, possibly by hormesis.     

联用阿米洛利与川芎嗪预防大鼠肝纤维化的实验研究

目的观察联用阿米洛利与川芎嗪对大鼠肝纤维化的预防效果。方法使用二甲基亚硝胺建立大鼠肝纤维化模型,观察给予阿米洛利与川芎嗪后,肝功能、丙二醛、超氧歧化酶、羟脯氨酸、透明质酸及层粘连蛋白含量变化。结果阿米洛利无改善肝功能之功效,川芎嗪可明显改善肝功能诸指标;阿米洛利和川芎嗪可明显降低血清透明质酸、层粘连蛋白和肝组织羟脯氨酸和丙二醛的含量(P<0.05);可明显提高肝组织内的超氧歧化酶的活力(P<0.01);尤以合用组效果最佳。结论阿米洛利与川芎嗪对二甲基亚硝胺诱导的肝纤维化均有预防作用,两者合用有一定协同作用。     

联用阿米洛利与川芎嗪预防大鼠肝纤维化的实验研究

目的观察联用阿米洛利与川芎嗪对大鼠肝纤维化的预防效果。方法使用二甲基亚硝胺建立大鼠肝纤维化模型,观察给予阿米洛利与川芎嗪后,肝功能、丙二醛、超氧歧化酶、羟脯氨酸、透明质酸及层粘连蛋白含量变化。结果阿米洛利无改善肝功能之功效,川芎嗪可明显改善肝功能诸指标;阿米洛利和川芎嗪可明显降低血清透明质酸、层粘连蛋白和肝组织羟脯氨酸和丙二醛的含量（P〈0.05）;可明显提高肝组织内的超氧歧化酶的活力（P〈0．01）;尤以合用组效果最佳。结论阿米洛利与川芎嗪对二甲基亚硝胺诱导的肝纤维化均有预防作用,两者合用有一定协同作用。     

Effects of anthocyanin-rich purple potato flakes on antioxidant status in F344 rats fed a cholesterol-rich diet

We examined the antioxidant effects of polyphenol/anthocyanin-rich potato (Solanum tuberosum cv. Shadow-Queen) flakes in male rats fed a high-cholesterol diet. The rats were served either a high-cholesterol (0.5% cholesterol plus 0.125% sodium cholate) diet, or a high-cholesterol diet containing a mixture of 243 g alpha-maize starch/kg supplemented with one of the following (per kg diet): 300 g medium purple potato (Shadow-Queen), 300 g white potato (Solanum tuberosum cv. Toyoshiro) or 300 g dark purple sweet potato (Ipomoea batatas cv. Ayamurasaki) flakes for 28 d. We analysed thiobarbituric acid reactive substance (TBARS) levels in the serum and liver, and antioxidant enzyme activities in the liver. At this dosage, TBARS levels in the serum and liver of the Shadow-Queen and Ayamurasaki groups were significantly lower than those in the control and Toyoshiro groups. The serum urate levels in all the flake groups were significantly lower than that in the control group. The hepatic glutathione levels in the Shadow-Queen and Ayamurasaki groups were significantly higher than in the control and Toyoshiro groups. The activities of hepatic glutathione reductase and glutathione S-transferase in the Shadow-Queen and Ayamurasaki groups were significantly greater than those in the control group. These results show that modulation of antioxidant enzymes and oxidative status in the serum and liver by the purple potato flake diet (Shadow-Queen) containing polyphenols/anthocyanins may play an important role in the protection against adverse effects related to oxidative damage in rats fed a high-cholesterol diet.     

补充VE、Se对大鼠肝纤维化和抗氧化功能影响的研究

目的 :　探讨维生素 E(VE)、硒 (Se)对 CCl4 大鼠肝纤维化和抗氧化功能的影响。方法 :　 48只 SD大鼠随机分为 3组。模型组 ,采用腹腔注射 5 0 % CCl4 和橄榄油混合制剂的方式建立大鼠肝纤维化模型 ,喂饲标准饲料 ;干预组 ,处理方式同前 ,并在大鼠饲料中加 VE(2 5 0 mg/kg )和 Se(0 .2 mg/kg)进行营养干预 ;对照组 ,腹腔注射生理盐水 ,喂饲标准饲料。全部动物于处理 8w后处死。通过 HE常规染色和 Masson三色胶原染色对肝组织切片进行病理组织学检查 ;同时分别检测大鼠体内各种抗氧化指标和其他肝纤维化指标 ,并观察其变化。结果 :　干预组大鼠抗氧化能力有显著提高 ,表现在肝组织和血清 SOD、红细胞 GPX活性均显著高于模型组 ,而肝组织和血清MDA水平显著低于模型组。同时 ,干预组大鼠的肝纤维化程度显著低于模型组 ,体现在血清 ALT、AST水平、肝组织羟脯氨酸含量都显著低于模型组 ;组织病理学检查显示肝脏胶原纤维增生程度也显著低于模型组。结论 :　补充适量 VE和 Se具有提高机体抗氧化的能力 ,显著减轻肝脏胶原纤维的增生程度     

Can apricot kernels fatty acids delay the atrophied hepatocytes from progression to fibrosis in dimethylnitrosamine (DMN)-induced liver injury in rats?

Background and aims

The present study was aimed to analyze the chemical composition of ground apricot kernel (GAK) and examine its effect on hepatic fibrosis in vivo induced by dimethylnitrosamine (DMN) in rats.

Methods and results

Hepatic fibrosis was induced by intraperitoneal injections of 10 mg/kg DMN for 3 consecutive days each week over a period of 4 wk. The rats were randomly assigned to five groups of nine rats each: the negative control group (NC), the hepatic fibrosis group (PC), hepatic fibrosis supplemented with GAK (0.5 mg/kg/BW/rat), hepatic fibrosis supplemented with GAK (1 mg/kg/BW/rat) and hepatic fibrosis supplemented with GAK (1.5 mg/kg/BW/rat). Rats were killed, blood was collected and livers were excised for biochemical measurements and histological examination. Results indicate that the diet supplemented with GAK led to improving liver function, lipid peroxides, and liver CAT, SOD and GSH. These results were confirmed by liver histology. Hierarchically high levels f GAK (1.5 mg/kg/BW/rat) gave the best results compared to other tested levels.

Conclusion

This study demonstrates that GAK administration specifically (1.5 mg/kg/BW/rat) can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis. Furthermore, a human trial would be applied specially GAK is a part of Egyptian diet. The act of why high amounts of GAK was improved biochemical values compared to low or moderate levels tested in this study may be due to increase levels of oleic acid and other polyphenols in apricot kernels

     

Soy protein retards the progression of non-alcoholic steatohepatitis via improvement of insulin resistance and steatosis

Objective

Non-alcoholic steatohepatitis (NASH) is a common cause of liver disease, and it may progress to fibrosis or cirrhosis. The aim of this study was to investigate the effects of soy protein on hepatic steatosis and insulin resistance in NASH.

Methods

Forty male Sprague-Dawley rats were fed a high-fat diet for 4 wk to induce NASH and then were allocated to one of four diets: a NASH-inducing diet, a standard diet, a NASH-inducing diet plus soy protein, and a standard diet plus soy protein.

Results

After the 10-wk experimental period, the results showed that soy protein significantly lowered plasma cholesterol concentrations and body fat accumulation. Soy protein intake also decreased the hepatic lipid depots of triacylglycerols and cholesterol and decreased the concentrations of lipid peroxides. In an analysis of antioxidative status, rats fed the soy protein diet showed improved antioxidative potential due to increases in superoxide dismutase and catalase activities and a decrease in the protein expression of cytochrome P450 2E1.

Conclusion

Soy protein may improve the liver function in patients with NASH by lowering lipid levels in the blood and liver, increasing the antioxidative capacity, and improving insulin resistance.     

甲乙煎对肝纤维化大鼠肝组织MMP2及TGFβ1表达的作用

目的观察中药甲乙煎对实验性肝纤维化大鼠基质金属蛋白酶 2（MMP2）及转化生长因子 1（TGFβ1）表达的作用。方法雄性清洁级Wister大鼠60只,随机分为正常对照组和肝纤维化模型组,运用二甲基亚硝胺对模型组大鼠诱导肝纤维化。4周后,将模型组大鼠随机分为模型对照组、甲乙煎高剂量［22 g/（kg·d）］组和低剂量［5.5 g／（kg·d）］组。对甲乙煎高、低剂量组大鼠分别给予甲乙煎灌胃,共治疗4周,处死全部大鼠。采用免疫组化法检测大鼠肝组织MMP2和TGFβ1的表达。结果经中药甲乙煎高、低剂量治疗后,甲乙煎高、低剂量组的大鼠肝细胞浆内TGFβ1的阳性表达与模型对照组比较,显著降低(P＜0.05),其中甲乙煎高剂量组优于低剂量组(P＜0.05);而甲乙煎高、低剂量组MMP2的表达较模型对照组无明显差异(P>0.05)。结论中药甲乙煎能下调实验性肝纤维化大鼠肝组织TGFβ1的表达,这是其抗肝纤维化的作用机制之一。     

Dietary selenomethionine increases exon-specific DNA methylation of the p53 gene in rat liver and colon mucosa

The regulation of site-specific DNA methylation of tumor suppressor genes has been considered as a leading mechanism by which certain nutrients exert their anticancer property. This study was to investigate whether selenium (Se) affects the methylation of globe genomic DNA and the exon-specific p53 gene. Three groups of rats (n = 6-7/group) were fed the AIN-93G basal diet supplemented with 0 [Se deficient (D)], 0.15 [Se adequate (A)], or 4 mg [Se supranutritional (S)] (Se as l-selenomethionine)/kg diet for 104 d, respectively. Rats fed the A or S diet had greater plasma and liver glutathione peroxidase activity, liver thioredoxin reductase activity, and plasma homocysteine concentration than those fed the D diet. However, compared with the A diet, rats fed the S diet did not further increase these Se-dependent enzyme activities or homocysteine concentration. In contrast, Se concentrations in kidney, liver, gastrocnemius muscle, and plasma were increased in a Se-dose-dependent manner. Interestingly, rats fed the S diet had significantly less global liver genomic DNA methylation than those fed the D diet. However, the S diet significantly increased the methylation of the p53 gene (exons 5-8) but not the β-actin gene (exons 2-3) DNA in liver and colon mucosa compared with those fed the D diet. Taken together, long-term Se consumption not only affects selenoprotein enzyme activities, homocysteine, tissue Se concentrations, and global genomic DNA methylation but also increases exon-specific DNA methylation of the p53 gene in a Se-dose-dependent manner in rat liver and colon mucosa.