Alterations to surfactant precede physiological deterioration during high tidal volume ventilation

Lung injury due to mechanical ventilation is associated with an impairment of endogenous surfactant. It is unknown whether this impairment is a consequence of or an active contributor to the development and progression of lung injury. To investigate this issue, the present study addressed three questions: Do alterations to surfactant precede physiological lung dysfunction during mechanical ventilation? Which components are responsible for surfactant's biophysical dysfunction? Does exogenous surfactant supplementation offer a physiological benefit in ventilation-induced lung injury? Adult rats were exposed to either a low-stretch [tidal volume (Vt) = 8 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O, respiratory rate (RR) = 54-56 breaths/min (bpm), fractional inspired oxygen (Fi(O2)) = 1.0] or high-stretch (Vt = 30 ml/kg, PEEP = 0 cmH2O, RR = 14-16 bpm, Fi(O2) = 1.0) ventilation strategy and monitored for either 1 or 2 h. Subsequently, animals were lavaged and the composition and function of surfactant was analyzed. Separate groups of animals received exogenous surfactant after 1 h of high-stretch ventilation and were monitored for an additional 2 h. High stretch induced a significant decrease in blood oxygenation after 2 h of ventilation. Alterations in surfactant pool sizes and activity were observed at 1 h of high-stretch ventilation and progressed over time. The functional impairment of surfactant appeared to be caused by alterations to the hydrophobic components of surfactant. Exogenous surfactant treatment after a period of high-stretch ventilation mitigated subsequent physiological lung dysfunction. Together, these results suggest that alterations of surfactant are a consequence of the ventilation strategy that impair the biophysical activity of this material and thereby contribute directly to lung dysfunction over time.     

Protective effects of elevated endogenous surfactant pools to injurious mechanical ventilation

Depletion of alveolar macrophages (AM) leads to an increase in endogenous surfactant that lasts several days beyond the repletion of AM. Furthermore, impairment to the endogenous pulmonary surfactant system contributes to ventilation-induced lung injury. The objective of the current study was to determine whether increased endogenous surfactant pools induced via AM depletion was protective against ventilation-induced lung injury. Adult rats were intratracheally instilled with either control or dichloromethylene diphosphonic acid (DMDP) containing liposomes to deplete AMs and thereby increase endogenous surfactant pools. Either 3 or 7 days following instillation, rats were exposed to 2 h of injurious ventilation using either an ex vivo or in vivo ventilation protocol and were compared with nonventilated controls. The measured outcomes were oxygenation, lung compliance, lavage protein, and inflammatory cytokine concentrations. Compared with controls, the DMDP-treated animals had significantly reduced AM numbers and increased surfactant pools 3 days after instillation. Seven days after instillation, AM numbers had returned to normal, but surfactant pools were still elevated. DMDP-treated animals at both time points exhibited protection against ventilation-induced lung injury, which included superior physiological parameters, lower protein leakage, and lower inflammatory mediator release into the air space, compared with animals not receiving DMDP. It is concluded that DMDP-liposome administration protects against ventilation-induced lung injury. This effect appears to be due to the presence of elevated endogenous surfactant pools.     

Effects of the diet consumed during the pregnancy on the lipids content in maternal and fetal rat lungs.

This study was designed to determine if the quantity of lipids in the diet fed to pregnant rats would affect the deposition of fat in the fetal lung. Wistar rats were fed with two different diets during pregnancy: Standard Diet (StD; 4.000 cal/g) and High Fat Carbohydrate Free Diet (HFCFD; 6.000 cal/g). The rats consumed daily the same amount of calories from these different diets. The concentrations of triglycerides (TG), phospholipids (PL), total, esterified and free cholesterol (TC, EC and FC, respectively) were determined in serum and lung from pregnant rats as well as from their 19 day old fetuses. In the serum of rats fed with HFCFD, the cholesterol concentration increased in relation to that of rats fed with StD. In pregnant rat lung, the PL concentrations decreased and the TC, EC and FC concentrations increased with HFCFD in relation to StD. The triglycerides were not modified in any case. The lipidic composition of the sera and fetal lung were not changed by the two diets consumed by pregnant rats. This may be a biological protective mechanism to assure an adequate synthesis of alveolar surfactant.     

Physiological study on the influence of some plant oils in rats exposed to a sublethal concentration of diazinon

The present study was aimed to evaluate the influence of olive, sesame and black seed oils on levels of some physiological parameters in male rats exposed to diazinon (DZN). Body weight changes, and levels of serum total protein, albumin, glucose, triglycerides, cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), atherogenic index (AI), atherogenic coefficient (AC), cardiac risk ratio (CRR), glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MAD) were selected as physiological parameters. The experimental animals were distributed into nine groups. Rats group exposed to DZN and fed with normal diet resulted in pronounced severe changes including reduced body weight gain rate, significantly increase in levels of serum albumin, glucose, cholesterol, LDL-C, AI, AC, CRR and MDA while levels of HDL-C, GSH and SOD were decreased. In rats treated with DZN, the supplementation of the olive, sesame and black seed oils showed remarkable lowering influences of physiological alterations. Moreover, the present results confirmed that these oils possess antioxidative effects against DZN toxicity. Finally, the present findings suggest that these oils are safe and promising agents for the treatment of physiological disturbances induced by DZN and may be also by other pollutants, and toxic and pathogenic factors.     

Exposure to Polymers Reverses Inhibition of Pulmonary Surfactant by Serum,Meconium, or Cholesterol in the Captive Bubble Surfactometer

Dysfunction of pulmonary surfactant in the lungs is associated with respiratory pathologies such as acute respiratory distress syndrome or meconium aspiration syndrome. Serum, cholesterol, and meconium have been described as inhibitory agents of surfactant’s interfacial activity once these substances appear in alveolar spaces during lung injury and inflammation. The deleterious action of these agents has been only partly evaluated under physiologically relevant conditions. We have optimized a protocol to assess surfactant inhibition by serum, cholesterol, or meconium in the captive bubble surfactometer. Specific measures of surface activity before and after native surfactant was exposed to inhibitors included i), film formation, ii), readsorption of material from surface-associated reservoirs, and iii), interfacial film dynamics during compression-expansion cycling. Results show that serum creates a steric barrier that impedes surfactant reaching the interface. A mechanical perturbation of this barrier allows native surfactant to compete efficiently with serum to form a highly surface-active film. Exposure of native surfactant to cholesterol or meconium, on the other hand, modifies the compressibility of surfactant films though optimal compressibility properties recover on repetitive compression-expansion cycling. Addition of polymers like dextran or hyaluronic acid to surfactant fully reverses inhibition by serum. These polymers also prevent surfactant inhibition by cholesterol or meconium, suggesting that the protective action of polymers goes beyond the mere enhancement of interfacial adsorption as described by depletion force theories.     

High oxygen concentrations predispose mouse lungs to the deleterious effects of high stretch ventilation.

Mechanical ventilation is a necessary intervention for patients with acute lung injury. However, mechanical ventilation can propagate acute lung injury and increase systemic inflammation. The exposure to >21% oxygen is often associated with mechanical ventilation yet has not been examined within the context of lung stretch. We hypothesized that mice exposed to >90% oxygen will be more susceptible to the deleterious effects of high stretch mechanical ventilation. C57B1/6 mice were randomized into 48-h exposure of 21 or >90% oxygen; mice were then killed, and isolated lungs were randomized into a nonstretch or an ex vivo, high-stretch mechanical ventilation group. Lungs were assessed for compliance and lavaged for surfactant analysis, and cytokine measurements or lungs were homogenized for surfactant-associated protein analysis. Mice exposed to >90% oxygen + stretch had significantly lower compliance, altered pulmonary surfactant, and increased inflammatory cytokines compared with all other groups. Our conclusion is that 48 h of >90% oxygen and high-stretch mechanical ventilation deleteriously affect lung function to a greater degree than stretch alone.     

Effects of pulmonary surfactant and surfactant protein A on phagocytosis of fractionated alveolar macrophages: relationship to starvation.

Pulmonary surfactant isolated from bronchoalveolar lavage fluid of rat lung contained a high content of surfactant protein A (SP-A) in starved for 2 days compared to fed controls, but this phenomena returned to baseline following more than 4 days starvation. As determined by immunoperoxidase staining of lung sections using SP-A antibody, SP-A could be consistently observed in nonciliated bronchiolar (Clara) cells, alveolar type II cells and some alveolar macrophages (AM). Fc receptor-mediated phagocytosis of AM was enhanced by SP-A, which was dependent on the dosis and reached a maximum at 10 micrograms of SP-A/ml. Antibody to SP-A completely inhibited the enhanced response of phagocytosis. When exposed AM subpopulations, separated into four fractions (I, II, III and IV) by discontinuous Percoll gradient, to SP-A or pulmonary surfactant prepared from rats fed and starved for 2 days enhanced their phagocytic activity in high dense cells (III and IV), particularly to SP-A and pulmonary surfactant from rats starved for 2 days. Whereas little change in lower dense fractions (I and II) were seen in all exposures except for SP-A that enhanced the cells of fraction II. These results supported the concept that pulmonary surfactant and its apoprotein, SP-A, are a factor to regulate lung defense system including activation of AM that undergo different processes following starvation.     

Effects of leukotriene inhibition on pulmonary morphology in rat pup lungs exposed to hyperoxia

Assisted ventilation is necessary for treating preterm infants with respiratory distress syndrome. Unfortunately, high and prolonged concentrations of oxygen associated with assisted ventilation often lead to pulmonary changes, such as hemorrhage and inflammation. The resulting chronic pulmonary condition is known as bronchopulmonary dysplasia. Pulmonary changes characteristic of this syndrome can be produced in rat pups exposed to high oxygen levels. We exposed 21-d-old rats to room air or continuous 95% oxygen for 7 d and then allocated them into 6 groups to evaluate whether treatment with zileuton and zafirlukast, 2 agents which decrease the effects of leukotrienes, lessened the pulmonary effects of short-term hyperoxia. After 7 d, lung tissue was collected for light and electron microscopy. Pulmonary changes including edema, hemorrhage, alveolar macrophage influx, and Type II pneumocyte proliferation were graded on a numerical scoring system. Compared with controls exposed to hyperoxia [corrected] and saline, rats exposed to hyperoxia and treated with zileuton had significantly reduced levels of alveolar macrophage influx and Type II pneumocyte proliferation, but those exposed to hyperoxia [corrected] and treated with zafirlukast showed no significant reduction in any pulmonary changes. This study helps define pulmonary changes induced secondary to hyperoxia in rat pups and presents new information on the mechanisms of leukotriene inhibition in decreasing the severity of hyperoxic lung injury.     

Involvement of phospholipase A2 in Pseudomonas aeruginosa-mediated PMN transepithelial migration

Oxidative damage to surfactant can decrease lung function in vivo. In the current study, our two objectives were: 1) to examine whether the adverse effects of oxidized surfactant would be accentuated in animals exposed to high tidal volume ventilation, and 2) to test whether supplementation with surfactant protein A (SP-A) could improve the function of oxidized surfactant in vivo. The first objective was addressed by evaluating the response of surfactant-deficient rats administered normal or oxidized surfactant and then subjected to low tidal volume (6 ml/kg) or high tidal volume (12 ml/kg) mechanical ventilation. Under low tidal volume conditions, rats administered oxidized surfactant had impaired lung function, as determined by lung compliance and arterial blood gas analysis, compared with nonoxidized controls. Animals subjected to high tidal volume ventilation had impaired lung function compared with low tidal volume groups, regardless of the oxidative status of the surfactant. The second experiment demonstrated a significantly superior physiological response in surfactant-deficient rats receiving SP-A containing oxidized surfactant compared with oxidized surfactant. Lavage analysis at the end of the in vivo experimentation showed no differences in the recovery of oxidized surfactant compared with nonoxidized surfactant. We conclude that minimizing excessive lung stretch during mechanical ventilation is important in the context of exogenous surfactant supplementation and that SP-A has an important biophysical role in surfactant function in conditions of oxidative stress. Furthermore, the oxidative status of the surfactant does not appear to affect the alveolar metabolism of this material.     

Effect of the ingestion of thermically treated fat on blood lipids and blood lipoproteins in the rat

The effect on rats fed on a diet with 15% solid frying fat (diet B) is compared to the effect of a diet with 15% of the same fat but in the raw state (diet A). After 10 weeks being fed on these diets serum triglycerides, phospholipids, total cholesterol, free cholesterol, esterified cholesterol, high density lipoprotein-cholesterol and free fatty acid levels were checked. Percentage of very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins as well as the composition of these lipoproteins was determined in parallel. Rats fed on diet B showed a significant increase in phospholipids and a significant decrease in VLDL when compared to those fed on diet A. Phospholipids on LDL decreased significantly in diet B fed rats. The data obtained seem to indicate that the hypercholesterolemic tendency induced by frying fat is neutralized by a decrease in VLDL levels.     

Effect of allicin from garlic powder on serum lipids and blood pressure in rats fed with a high cholesterol diet

The use of fresh aqueous garlic extract is known to be effective in reducing thromboxane formation by platelets in both in vivo and in vitro animal models of thrombosis. In the present study, we studied the effect of Lichtwer garlic powder (containing 1.3% alliin equivalent to 0.6% allicin) on the serum cholesterol, triglyceride, glucose, protein, and systolic blood pressure in rats fed with a high cholesterol diet. Experimental rats were fed a 2% high cholesterol diet with and without garlic powder for 6 weeks. Control rats were fed a normal diet. The aqueous garlic powder extract was given orally to rats on a daily basis. It was observed that cholesterol-fed animals had a significant increase in serum cholesterol compared to the control group of rats fed on a normal diet. However, when the rats were fed with a high cholesterol diet mixed with garlic powder, there was a significant reduction in their serum cholesterol levels compared with the group which were on a diet containing high cholesterol without garlic powder. Serum triglyceride levels were also significantly lowered by garlic powder when compared to control and high cholesterol diet group rats. The blood pressure of the high cholesterol diet animals was significantly higher compared to the animals receiving the control diet. The blood pressure of the animals receiving garlic powder and high cholesterol diet was significantly lower as compared to the high cholesterol and control diet group. No significant changes were observed in the serum glucose and protein in all of the rats. These results show that garlic is beneficial in reducing blood cholesterol, triglycerides levels and systolic blood pressure in hypercholesterolemic rats. Our experimental results show that garlic may beneficially affect two risk factors for atherosclerosis--hyperlipidemia and hypertension.     

Diets alter jejunal morphology and brush border membrane composition in streptozotocin-diabetic rats

Previous studies have demonstrated enhanced active and passive uptake of many nutrients in animals with experimental diabetes. These changes in absorption cannot be explained by differences in intestinal morphology, although the brush border membrane (BBM) phospholipids do change in diabetes. Manipulation of diet produces alterations in intestinal uptake of lipids and glucose. This study was undertaken to determine the effect of diet and diabetes on jejunal morphology and BBM lipid composition. Rats were rendered hyperglycemic with streptozotocin and were fed for 2 weeks on a diet that was high or low in carbohydrate, essential fatty acids, cholesterol, or protein. In both control and diabetic rats, these diets produced changes in villus height and BBM sucrase and alkaline phosphatase activities. In both control and diabetic rats, BBM phospholipids were unaffected by changes in the dietary content of essential fatty acids, cholesterol, or protein, but total BBM phospholipid content was reduced in animals fed low as compared with high carbohydrate diet. Total BBM phospholipid content was higher in diabetic than in control animals fed the low protein diet, whereas BBM phospholipid content was lower in diabetic than in control animals fed the high carbohydrate diet, and was even lower in diabetic animals fed the low as compared with the high carbohydrate diet. These changes in total phospholipids were due to alterations in the BBM content of phospholipids containing choline. In control animals, BBM cholesterol was higher in rats fed the low as compared with the high cholesterol diet, or the low as compared with the high protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of phytate in soy protein on the serum and liver cholesterol levels and liver fatty acid profile in rats

Dietary soy protein, in comparison with casein, generally lowers the serum cholesterol concentration in rats fed on a cholesterol-enriched diet, while mixed results were observed in rats fed on a diet free of cholesterol. Soy protein also suppresses the conversion of linoleic acid to arachidonic acid in the rat liver. The present study examines whether phytate, a minor component of a soy protein isolate, is responsible for these beneficial effects of soy protein. Weanling male rats were fed for 4 weeks on a purified diet containing a 20% level of protein (either casein (CAS), soy protein (SOY), phytate-depleted SOY (PDSOY) or phytate-replenished PDSOY (PRSOY)) and cholesterol (0 or 0.5%). The dietary protein source and phytate level only affected the serum and liver cholesterol concentrations when the animals were fed on the cholesterol-enriched diet, being significantly lower in those rats fed on the SOY and PRSOY diets than in those fed on the CAS diet, while the concentrations in the rats fed on the PDSOY diet were intermediate. When the animals were fed on the cholesterol-free diet, the ratio of (20:3n-6 + 20:4n-6)/18:2n-6 in liver phosphatidylcholine, a delta6 desaturation index, was significantly lower in the SOY diet group than in the CAS, PDSOY and PRSOY diet groups. Dietary cholesterol significantly depressed the ratio, but neither depletion nor replenishment of phytate affected the ratio. These results suggest that phytate in soy protein played a limited role in the cholesterol-lowering effect of soy protein and was not involved in the metabolism of linoleic acid.     

Vitamin A deficiency alters rat lung alveolar basement membrane Reversibility by retinoic acid

Vitamin A is essential for lung development and pulmonary cell differentiation and its deficiency results in alterations of lung structure and function. Basement membranes (BMs) are also involved in those processes, and retinoic acid, the main biologically active form of vitamin A, influences the expression of extracellular matrix macromolecules. Therefore, we have analyzed the ultrastructure and collagen content of lung alveolar BM in growing rats deficient in vitamin A and the recovering effect of all-trans retinoic acid. Male weanling pups were fed a retinol-adequate or -deficient diet until they were 60 days old. A group of vitamin A-deficient pups were recovered by daily intraperitoneal injections of all-trans retinoic acid for 10 days. Alveolar BM in vitamin A-deficient rats doubled its thickness and contained irregularly scattered collagen fibrils. Immunocytochemistry revealed that these fibrils were composed of collagen I. Total content of both collagen I protein and its mRNA was greater in vitamin-deficient lungs. In agreement with the greater size of the BM the amount of collagen IV was also increased. Proinflammatory cytokines, IL-1α, IL-1β and TNF-α, did not change, but myeloperoxidase and TGF-β1 were increased. Treatment of vitamin A-deficient rats with retinoic acid reversed all the alterations, but the BM thickness recovered only partially. Retinoic acid recovering activity occurred in the presence of increasing oxidative stress. In conclusion, vitamin A deficiency results in alterations of the structure and composition of the alveolar BM which are probably mediated by TGF-β1 and reverted by retinoic acid. These alterations could contribute to the impairment of lung function and predispose to pulmonary disease.     

Effect of exogenous surfactant instillation on experimental acute lung injury

Pulmonary surfactant replacement has previously been shown to be effective in the human neonatal respiratory distress syndrome. The value of surfactant replacement in models of acute lung injury other than quantitative surfactant deficiency states is, however, uncertain. In this study an acute lung injury model using rats with chronic indwelling arterial catheters, injured with N-nitroso-N-methylurethane (NNNMU), has been developed. The NNNMU injury was found to produce hypoxia, increased mortality, an alveolitis, and alterations in the pulmonary surfactant system. Alterations of surfactant obtained by bronchoalveolar lavage included a reduction in the phospholipid-to-protein ratio, reduced surface activity, and alterations in the relative percentages of the individual phospholipids compared with controls. Treatment of the NNNMU-injured rats with instilled exogenous surfactant (Survanta) improved oxygenation; reduced mortality to control values; and returned the surfactant phospholipid-to-protein ratio, surface activity, and, with the exception of phosphatidylglycerol, the relative percentages of individual surfactant phospholipids to control values.     

Effect of Dietary Composition on Lipids in Serum and in Liver of Rats Fed a Cystine-excess Diet

The effects of dietary composition on lipids in serum and in liver of rats fed with a cystine- excess diet were investigated.

When starch was used as the carbohydrate source, the addition of excess-cystine caused an increase in serum cholesterol and phospholipids, and hepatomegaly. Phospholipids in serum of rats fed with a cystine-excess diet containing 5% corn oil were higher than those with a cystine-excess diet that was low in corn oil (0.1 %). The addition of konjac mannan and pectin prevented hypercholesterolemia, and the rise in phospholipids in serum was prevented by the addition of konjac mannan.

Liver cholesterol (mg/liver/100 g of body wt.) increased in rats fed with a cystine-excess diet.

The addition of excess cystine to a diet containing sucrose as the carbohydrate source resulted in a marked increase of cholesterol in serum and liver, and a decrease of serum triglycerides.

The replacement of starch by sucrose in the cystine-excess diet increased liver cholesterol.

Lipids, cholesterol, phospholipids and triglycerides in the liver, but not phospholipids, when expressed as mg per g of liver for rats fed with the diets containing sucrose, increased when compared to those for rats fed with the diets containing starch. In contrast, serum triglycerides increased.     

Increase of bile acids synthesis and excretion caused by taurine administration prevents the ovariectomy-induced increase in cholesterol concentrations in the serum low-density lipoprotein fraction of Wistar rats

We examined the effect of dietary taurine on the concentrations of serum cholesterol and apolipoprotein in lipoprotein fractions of Six-month-old ovariectomized, which were used as a model of hypercholesterolemia in postmenopausal woman, or sham operated rats. Taurine significantly reduced the serum total and low-density lipoprotein cholesterol concentrations only in the ovariectomized rats. In contrast, taurine significantly lowered the serum apolipoprotein B concentration and serum very low-density lipoprotein-apolipoprotein E concentration only in the sham operated rats. The serum total and high density lipoprotein-apolipoprotein E concentrations were significantly lower in the rats fed taurine than in those fed the control diet regardless of whether they had undergone ovariectomy. The esterified cholesterol level in the liver was significantly lower and the level of hepatic cholesterol 7 alpha-hydroxylase activity was significantly higher in the rats fed taurine than in those fed the control diet. The total bile acids concentration in the feces and intestinal contents of rats fed taurine were significantly higher than those in rats fed the control diet regardless of whether they had undergone ovariectomy. In the sham-rats, taurine accelerated bile acid synthesis and excretion, thereby increasing cholesterol consumption. The increased cholesterol consumption might be compensated by accelerating cholesterol synthesis and/or reducing the synthesis and release of very low-density lipoprotein from the liver. But in the ovariectomized rats, although taurine also accelerated bile acid synthesis and excretion, cholesterol demand might be compensated by excess cholesterol in the blood.     

Vitamin A deficiency disturbs collagen IV and laminin composition and decreases matrix metalloproteinase concentrations in rat lung. Partial reversibility by retinoic acid

Vitamin A is essential for lung development and pulmonary cell differentiation. Its deficiency leads to altered lung structure and function and to basement membrane architecture and composition disturbances. Previously, we showed that lack of retinoids thickens the alveolar basement membrane and increases collagen IV, which are reversed by retinoic acid, the main biologically active vitamin A form. This study analyzed how vitamin A deficiency affects the subunit composition of collagen IV and laminin of lung basement membranes and pulmonary matrix metalloproteinase content, plus the recovering effect of all-trans-retinoic acid. Male weanling pups were fed a retinol-adequate/-deficient diet until 60 days old. A subgroup of vitamin-A-deficient pups received daily intraperitoneal all-trans-retinoic acid injections for 10 days. Collagen IV and laminin chain composition were modified in vitamin-A-deficient rats. The protein and mRNA contents of chains α1(IV), α3(IV) and α4(IV) increased; those of chains α2(IV) and α5(IV) remained unchanged; and the protein and mRNA contents of laminin chains α5, β1 and γ1 decreased. The mRNA of laminin chains α2 and α4 also decreased. Matrix metalloproteinases 2 and 9 decreased, but the tissue inhibitors of metalloproteinases 1 and 2 did not change. Treating vitamin-A-deficient rats with retinoic acid reversed all alterations, but laminin chains α2, α4 and α5 and matrix metalloproteinase 2 remained low. In conclusion, vitamin A deficiency alters the subunit composition of collagen IV and laminin and the lung's proteolytic potential, which are partly reverted by retinoic acid. These alterations could contribute to impaired lung function and predispose to pulmonary disease.     

Effect of Curcuma kwangsiensis polysaccharides on blood lipid profiles and oxidative stress in high-fat rats

We have investigated the protective effect of polysaccharides from Curcuma kwangsiensis (CKP) against oxidative injury in rats fed high-fat diet. The protective effect of CKP was compared with Lovastatin, a well-known antioxidant. Sixty SD rats were used for the experimental study. Oxidative injury was induced by feeding high-fat diet for 3 weeks. The blood profiles, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-c) levels during experimental period were significantly increased in untreated model control group, whereas high-density lipoprotein cholesterol (HDL-c) levels and antioxidant enzymes activities significantly decreased in untreated model control group. The levels of TC, TG, LDL-c levels in CKP-treated rats were decreased significantly when compared to the untreated model control group, which were brought down to near normal in CKP-treated group. HDL-c level and antioxidant enzymes activities were found to be significantly increased in serum of CKP-treated group compared to the untreated model control group. The protective effect of CKP against oxidative injury was comparable to that of Lovastatin. Our data suggest that CKP exerts its protective effect by modulating the extent of lipid peroxidation and augmenting antioxidant defense system and thus protects the experimental animals against oxidative injury induced by high-fat diet treatment.     

Supplementation of orotic acid to the casein, but not to egg protein, soy protein, or wheat gluten diets, increases serum ornithine carbamoyltransferase activity

Effects of dietary supplementation of orotic acid to a diet containing the casein protein were compared with diets containing egg protein, soy protein, or wheat gluten on lipid levels in the liver and serum and activities of ornithine carbamoyltransferase (OCT) and alanine aminotransferase in the serum of rats. We found that supplementation of orotic acid to each diet increased the contents of the liver total lipids, triacylglycerol, and phospholipids compared with those not supplemented. The contents of liver total lipids, triacylglycerol, cholesterol, and phospholipids in rats fed the casein diet were significantly higher than those of rats fed the other three diets when orotic acid was supplemented. The levels of triacylglycerol, cholesterol, and phospholipids in the serum of rats fed the casein diet were markedly decreased by addition of orotic acid. The supplementation of orotic acid significantly increased the activities of both serum OCT and alanine aminotransferase in rats fed the casein diet, but not in rats fed the other diets. In conclusion, liver lipid accumulation induced by dietary orotic acid depends on the type of dietary protein. The enhancement of serum OCT activity may result from liver lipid accumulation in rats fed the casein diet supplemented with orotic acid, demonstrating hepatic damage.