Bioefficacy of β-carotene is improved in rats after solubilized as equimolar dose of β-carotene and lutein in phospholipid-mixed micelles

β-Carotene (BC) is a potent dietary source of vitamin A for populations at risk of vitamin A deficiency, yet its bioavailability is influenced by several factors such as dietary fat, carotenoids type, and other components. We hypothesize that type of micellar phospholipids influence bioefficacy of carotenoids and activity of carotenoid metabolizing enzymes. This study determined the BC bioefficacy in rats (n = 5/time point) after an equimolar dose of BC and lutein (Lut) solubilized in micelles containing either phosphatidylcholine (PC) or lysophosphatidylcholine (LPC), or no phospholipid (NoPL). Results show that no BC and Lut was detected in the plasma of rats at 0 hour, but after gavage, the mean (SD) area under the curve (AUC; in picomoles per milliliter) of plasma BC for 6 hours in PC, LPC, and NoPL groups were 1145 (132), 965 (199), and 2136 (112), respectively. The AUC value of plasma Lut in LPC group (183 ± 23 pmol mL⁻¹ h⁻¹) was higher than the other 2 groups. Similarly, liver BC and Lut levels in the LPC group were significantly higher than the other groups. The activity of BC 15,15′-monooxygenase in the intestinal mucosa of LPC and PC groups was higher than NoPL group. Plasma retinyl palmitate level in LPC (AUC, 647 ± 89 pmol mL⁻¹ h⁻¹) group was 2-fold higher than that of PC and NoPL groups. Results indicate that phospholipids enhanced the BC and Lut absorption. β-Carotene uptake was not affected by Lut when given with micellar phospholipids, but reduced plasma Lut level was observed, which may be due to the conversion of absorbed Lut into its metabolites.     

Effect of Storage on Organoleptic Characteristics and Nutritional Evaluation of β -Carotene and Iron-Rich Products

Vitamin A deficiency and iron deficiency anaemia are two major micronutritional disorders of national importance affecting the vulnerable groups of the population. In the present study an effort has been made to combat this problem by developing β -carotene and iron-rich products, namely biscuits and shakarpara by adding cauliflower leaves powder and these were stored to see the effect of storage on their organoleptic and nutritional evaluation. Fresh biscuits and shakarpara were found organoleptically acceptable, whereas the mean scores of organoleptic characteristics decreased gradually after 60 days of storage. Moisture, protein, fat, crude fibre, minerals, carbohydrates and energy contents were 2.98 g, 8.49 g, 20.90 g, 0.90 g, 1.38 g, 65.35 g and 2025 kJ/100 g in biscuits and 6.22 g, 5.38 g, 23.80 g, 0.42 g, 1.08 g, 63.10 g and 2042 kJ/100 g in shakarpara, on fresh weight basis, respectively. β -Carotene content was 1.42 mg/100 g in biscuits and 1.55 mg/100 g in shakarpara, which decreased significantly after 60 days of storage. Total iron content was 7.16 mg/100 g in biscuits and 8.44 mg/100 g in shakarpara. Soluble iron, ionizable iron andin vitro iron at pH 7.50 in biscuits were 2.84 mg/100 g, 1.25 mg/100 g and 8.70% of total iron and inshakarpara 9.96 mg/100g, 1.75 mg/100 g and 10.24% of total iron, respectively, which decreased significantly after 60 days of storage in both products. These products can be stored for up to 30 days without any significant change in organoleptic and nutritional characteristics.     

β-胡萝卜素遗传毒性研究

目的探讨β-胡萝卜素的遗传毒性,为其安全使用提供科学依据。方法 Ames试验,采用平板掺入法,分加和不加代谢激活系统S9 2组平行试验,受试物设5个剂量组,计数各组回变菌落数;骨髓嗜多染红细胞微核试验,受试物设3个剂量组,检测骨髓嗜多染红细胞微核率;小鼠精子畸形试验,受试物设3个剂量组,观察不同剂量的β-胡萝卜素致小鼠精子畸形的数目。上述试验均设阴性对照组和阳性对照组。Ames试验另设一组空白对照组。结果 Ames试验,β-胡萝卜素各剂量组引起的回变菌落数未超过空白对照组自发回变菌落数的1倍以上;骨髓嗜多染红细胞微核试验,受试物各剂量组微核率与阴性对照组之间差异无统计学意义(P0.05),而阳性对照组与阴性对照组之间差异有统计学意义(P0.01);小鼠精子畸形试验,受试物各剂量组小鼠精子畸形率与阴性对照组之间差异无统计学意义(P0.05),而阳性对照组与阴性对照组之间差异有统计学意义(P0.01)。结论β-胡萝卜素对所试菌株、小鼠体细胞及生殖细胞无诱变性。     

Beta-carotene (provitamin A) decreases the severity of CCl4-induced hepatic inflammation and fibrosis in rats

Earlier data from experiments in rats have shown that administration of retinyl esters (vitamin A) strongly influences the effects of CCl₄ on the liver. The accumulation of collagen was inhibited, but an increase in CCl₄-toxicity with high mortality was observed. The present study was conducted to examine the effects of β-carotene (provitamin A) on CCl₄-related general and hepatic toxicity in rats. Oral administration of β-carotene during CCl₄-treatment resulted, biochemically, in a significantly lower increase in the hydroxyproline liver content and, histopathologically, in less severe liver fibrosis as compared with the liver of rats not treated with β-carotene. The study also showed that β-carotene administration could prevent the long-term loss of retinoids from the CCl₄-injured liver. No significant toxic effects of β-carotene, as previously found with retinyl esters (vitamin A), were observed. This experimental study suggests that β-carotene has the therapeutic potential to decrease the severity of liver fibrosis without marked toxicity.     

Altered retinol status and expression of retinol-related proteins in streptozotocin-induced type 1 diabetic model rats

Diabetes is a metabolic disorder characterized by chronic hyperglycemia. Advanced diabetes is associated with severe complications and impaired nutritional status. Here, we assessed the expression of retinol-associated proteins, including β-carotene 15,15''-monooxygenase (BCMO), lecithin:retinol acyltransferase (LRAT), aldehyde dehydrogenase (ALDH), and cytochrome P450 26A1 (CYP26A1), and measured retinol levels in the plasma and liver of streptozotocin (STZ)-induced type 1 diabetic model rats. Compared to the levels in the control rats, retinol levels in the plasma and liver of STZ rats were decreased and increased, respectively. Hepatic expression of the LRAT gene in STZ rats was lower than that in the controls. In the liver of STZ rats, the expression of ALDH1A1, a retinal metabolizing enzyme was higher, whereas ALDH1A2 expression was lower than in the controls. Hepatic CYP26A1 expression in STZ rats was significantly higher than in the control rats. BCMO expression levels in the liver and intestine of STZ rats were much lower than those of the controls. Altered BCMO expression might affect retinol status. It is considered that the metabolic availability of retinol was lessened despite the accelerated catabolism of retinol; therefore, retinol mobilization may be unbalanced in the liver of rats in the type 1 diabetic state.     

ON THE MECHANISM OF β-CAROTENE CONVERSION TO VITAMIN A

The central mechanism of β-carotene cleavage to retinal has been challenged by investigators using nonisotopic techniques.     

Eat more carrots? Dampening cell death in ethanol-induced liver fibrosis by β-carotene

Alcoholic liver disease (ALD) represents one of the principal causes of liver damage in humans. Long-term ethanol abuse leads to progressive liver injury and tissue remodeling, including steatosis, inflammation, fibrosis, cirrhosis and increased risk for hepatocellular carcinoma (HCC) development. Oxidative stress and subsequent liver cell death has long been identified as one of the key mechanisms during ALD progression, therefore antioxidants may display promising treatment options. In this issue of Hepatobiliary Surgery and Nutrition (HBSN), Peng et al. demonstrate that oral supplementation with β-carotene during chronic ethanol feeding in rats reduces oxidative stress, apoptotic cell death and inflammation. Reducing hepatocyte apoptosis, a major trigger for fibrogenesis and tumorigenesis, would make β-carotene a prospective target for treatment. However, before translating the promising findings of Peng and colleagues into clinical scenarios, it needs to be determined which cell death pathways, including necrosis and necroptosis, are affected by β-carotene, which liver cell populations are targeted by this vitamin A precursor, how specific the effects are for ALD in comparison to non-alcoholic steatohepatitis (NASH) or other chronic liver diseases, and whether reduced hepatic oxidative stress and apoptosis upon β-carotene supplementation truly relate to beneficial long-term consequences with respect to fibrosis, cirrhosis or HCC development.     

Diminished phospholipid incorporation of essential fatty acids in peripheral blood leucocytes from patients with Crohn's disease: correlation with zinc depletion.

Peripheral blood leucocytes from patients with Crohn's disease have been shown to have lower zinc content than those from a normal population. Since zinc influences essential fatty acid metabolism, incorporation of 14C-linoleic and 3H-arachidonic acids was studied in peripheral blood leucocytes from controls and patients with Crohn's disease. The zinc content of the leucocytes was also measured. After incubation for 2 h, content of 3H-arachidonic acid, but not 14C-linoleic acid, was greater in Crohn's disease leucocytes than in controls. In the Crohn's disease leucocytes, incorporation of both labelled fatty acids into the phosphatidylcholine fraction was significantly lower than in controls, whereas the amount of both fatty acids remaining in the leucocytes as free fatty acids was increased by 70%. In Crohn's disease, leucocyte zinc level was positively associated with the percentage of 3H-arachidonic acid incorporation into phosphatidylcholine. We conclude that peripheral blood leucocytes from patients with Crohn's disease have abnormal essential fatty acid metabolism and that 3H-arachidonic acid incorporation into the phosphatidylcholine fraction of leucocyte lipids in Crohn's disease varies as the zinc content of the leucocytes.     

Serum Levels of Alpha-Tocopherol,Vitamin C,Beta-Carotene,and Retinol in Malignant Pleural Mesothelioma

The aim of this study was to investigate the possible relationship between antioxidant vitamin levels andmalignant pleural mesothelioma (MPM). For this purpose, we measured the serum levels of 4 antioxidantvitamins, β-carotene, α-tocopherol, retinol, and ascorbic acid, in patients with environmentally induced MPMand in healthy controls from one tremolite village (Kureysler), the biggest erionite village (Tuzkoy) and Ankara.A total of 160 subjects were enrolled in the study, 42 (26.3%) diagnosed with MPM and 118 (73.7%) healthysubjects. A comparison was made between the MPM group and three control groups of which two were exposedand one was unexposed to mineral fibers. The study population consisted of 82 males (51%) and 78 females(49%) with a mean of age of 44.8±14 years (range; 20-65 years). Lowest levels of β-carotene, ascorbic acid, andα-tocopherol were found in MPM patients (MPM vs control groups combined, p<0.0001 for each antioxidantvitamin), without any relation to age or sex. There was no significant difference between the antioxidant levels ofhealthy controls of Tuzkoy and Ankara. In conclusion; our findings suggested an increased risk of MPM beingassociated with low levels of α-tocopherol and ascorbic acid in patients with MPM.     

Barrett’s Esophagus and β-carotene Therapy: Symptomatic Improvement in GERD and Enhanced HSP70 Expression in Esophageal Mucosa

Introduction: Epidemiological studies suggest a protective role for β-carotene with several malignancies. Esophageal adenocarcinoma frequently arises from Barrett’s esophagus (BE). We postulated that β-carotene therapy maybe protective in BE. Materials and Method: We conducted a prospective study in which 25 mg of β-carotene was administered daily for six-months to six patients. Each patient underwent upper endoscopy before and after therapy and multiple mucosal biopsies were obtained. Additionally, patients completed agastroesophageal reflux disease (GERD) symptoms questionnaire before and after therapy and severity score was calculated. To study the effect of β-carotene at molecular level, tissue extracts of the esophageal mucosal biopsywere subjected to assessment of heat-shock protein 70 (HSP70). Results: A significant (p<0.05) reduction in mean GERD symptoms severity score from 7.0±2.4 to 2.7±1.7 following β-carotene therapy was noted. Measurementof Barrett’s segment also revealed a significant reduction in mean length after therapy. In fact, two patients had complete disappearance of intestinal metaplasia. Furthermore, marked enhancement of HSP70 expression wasdemonstrated in biopsy specimens from Barrett’s epithelium in four cases that were tested. Conclusions: Longterm β-carotene therapy realizes amelioration of GERD symptoms along with restitution of the histological and molecular changes in esophageal mucosa of patients with BE, associated with concurrent increase in mucosal HSP70 expression.