Unraveling the impact of melatonin treatment: Oxidative stress, metabolic responses, and morphological changes in HuH7.5 hepatocellular carcinoma cells.

In addition to its highly aggressive nature and late diagnosis, hepatocellular carcinoma (HCC) does not respond effectively to available chemotherapeutic agents. The search is on for an ideal and effective compound with low cost and minimal side effects that can be used as an adjunct to chemotherapeutic regimens. One of the mechanisms involved in the pathology of HCC is the oxidative stress, which plays a critical role in tumor survival and dissemination. Our group has already demonstrated the antitumor potential of melatonin against HuH 7.5 cells. In the present study, we focused on the effects of melatonin on oxidative stress parameters and their consequences on cell metabolism. HuH 7.5 cells were treated with 2 and 4 mM of melatonin for 24 and 48 h. Oxidative stress biomarkers, antioxidant enzyme, mitochondrial membrane potential, formation of lipid bodies and autophagic vacuoles, cell cycle progression, cell death rate and ultrastructural cell alterations were evaluated. The treatment with melatonin increased oxidative stress biomarkers and reduced antioxidant enzyme activities of HuH 7.5 cells. Additionally, melatonin treatment damaged the mitochondrial membrane and increased lipid bodies and autophagic vacuole formation. Melatonin triggered cell cycle arrest and induced cell death by apoptosis. Our results indicate that the treatment of HuH 7.5 cells with melatonin impaired antioxidant defense systems, inhibited cell cycle progression, and caused metabolic stress, culminating in tumor cell death.

Effects of Bauhinia forficata on glycaemia, lipid profile, hepatic glycogen content and oxidative stress in rats exposed to Bisphenol A.

Bisphenol A (BPA) is an abundant raw material applied in the production of daily necessities, such as food cans, baby bottles, electronic and medical equipment. Phytotherapeutic use of plant preparations has long been known for multiple target medicinal uses. The species Bauhinia forficata is widely used as hypoglycemic, anti-inflammatory, antioxidant, diuretic and hypocholesterolemic agent. The aim of this study was to verify the effects of B. forficata extract in association with BPA exposure on serological parameters, hepatic antioxidant status and glycogen store capacity in Wistar rats. B. forficata was able to reduce BPA-induced glucose levels; it also prevented the early glucose elevation in control and BPA-exposed animals after the glucose provocative test. This effect was related to the hepatic glycogen content; while BPA reduced the hepatic glycogen deposits B. forficata treatment contributed to minimize it. BPA and B. forficata singly caused elevation in triacylglycerol and VLDL levels and reduction in cholesterol and LDL concentrations. BPA increased hepatic malondialdehyde levels and reduced catalase activity, thus inducing liver oxidative stress. Conversely, B. forficata treatment reduced malondialdehyde concentration without interfering with catalase activity; this antioxidant capacity is attributed to the flavonoids content (e.g., kaempferol and myricetin). Based on these results, we demonstrated that B. forficata commercial extract has hypoglycemic and antioxidant properties capable of minimizing the effects of BPA. However, it should be considered that the consumption of herbal commercial extract must be judicious to avoid deleterious health effects.

N-acetylcysteine an allium plant compound improves high-sucrose diet-induced obesity and related effects.

This study was designed to determine whether N-acetylcysteine (NAC, C(5)H(9)-NO(3)S), a compound from Allium species may be used as a complementary therapeutic agent, to inhibit high-sucrose induced-obesity and its effects on glucose tolerance, in vivo low-density lipoprotein (LDL)-oxidation and serum oxidative stress in rats. Initially, 24 male Wistar rats were divided into two groups: controls receiving standard chow (C, n = 6) and those receiving high-sucrose diet (HS, n = 18). After 22 days, (HS) group was divided into three groups (n = 6/group); (HS-HS) continued to eat high-sucrose diet and water; (HS-N) continued to eat high-sucrose diet and received 2 mg l(-1)-NAC in its drinking water; (HS-CN) changing high-sucrose to standard chow and receiving 2 mg l(-1)-NAC in its drinking water. After 22 days of the HS-group division (44 days of experimental period) body weight, body mass index and surface area were enhanced in HS-HS rats (P < .001). HS-HS rats had glucose intolerance, increased serum triacylglycerol (TG), very low-density lipoprotein (VLDL), oxidized-LDL (ox-LDL) and lipid-hydroperoxide (LH) than the others (P < .01). NAC in HS-N and HS-CN rats reduced the obesity markers, feed efficiency, LH and ox-LDL, as well normalized glucose response, TG and VLDL (P < .01) in these groups compared with HS-HS. Total antioxidant substances, GSH/GSSG ratio and glutathione-reductase, were higher in HS-N than in HS-HS (P < .01). In conclusion, NAC improved high-sucrose diet-induced obesity and its effects on glucose tolerance, lipid profile, in vivo LDL-oxidation and serum oxidative stress, enhancing antioxidant defences. The application of this agent may be feasible and beneficial for high-sucrose diet-induced obesity, which certainly would bring new insights on obesity-related adverse effects control.

Effects of olive oil and its minor phenolic constituents on obesity-induced cardiac metabolic changes.

BACKGROUND: Olive oil and its minor constituents have been recommended as important dietary therapeutic interventions in preventive medicine. However, a question remains to be addressed: what are the effects of olive oil and its phenolic compounds on obesity-induced cardiac metabolic changes? METHODS: Male Wistar rats were divided into two groups (n = 24/group): (C) receiving standard-chow; (Ob) receiving hypercaloric-chow. After 21 days C and Ob groups were divided into four subgroups (n = 6/group):(C) standard-chow and saline; (C-Olive)standard-chow and olive-oil (3.0 g/kg.day); (C-Oleuropein)standard-chow and oleuropein (0.023 mg/kg/day); (C-Cafeic) standard-chow and cafeic-acid (2.66 mg/kg/day); (Ob)receiving hypercaloric-chow and saline;(Ob-Olive) hypercaloric-chow and olive-oil;(Ob-Oleuropein) hypercaloric-chow and oleuropein;(Ob-Cafeic) hypercaloric-chow and cafeic-acid. Treatments were given twice a week during 21 days. RESULTS: After 42 days, obesity was evidenced in Ob rats from enhanced body-weight, surface-area, and body-mass-index. Energy-expenditure, oxygen consumption(VO2) and fat-oxidation were lower in Ob-group than in C. Despite no morphometric changes, Ob-Olive, Ob-Oleuropein and Ob-Cafeic groups had higher VO2, fat-oxidation, myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and lower respiratory-quotient than Ob. Citrate-synthase was highest in Ob-Olive group. Myocardial lipid-hydroperoxide(LH) and antioxidant enzymes were unaffected by olive-oil and its compounds in obesity condition, whereas LH was lower and total-antioxidant-substances were higher in C-Olive and C-Oleuropein than in C. CONCLUSIONS: The present study demonstrated for the first time that olive-oil, oleuropein and cafeic-acid enhanced fat-oxidation and optimized cardiac energy metabolism in obesity conditions. Olive oil and its phenolic compounds improved myocardial oxidative stress in standard-fed conditions.

Conjugated linoleic acid and cardiac health: oxidative stress and energetic metabolism in standard and sucrose-rich diets.

Studies on conjugated linoleic acid ingestion and its effect on cardiac tissue are necessary for the safe utilization of this compound as supplement for weight loss. Male Wistar 24-rats were divided into four groups (n=6):(C)given standard chow, water and 0.5 ml saline, twice a week by gavage; (C-CLA)receiving standard chow, water and 0.5 ml of conjugated linoleic acid, twice a week, by gavage; (S)given standard chow, saline by gavage, and 30% sucrose in its drinking water; (S-CLA)receiving standard chow, 30% sucrose in its drinking water and conjugated linoleic acid. After 42 days of treatment S rats had obesity with increased abdominal-circumference, dyslipidemia, oxidative stress and myocardial lower citrate synthase(CS) and higher lactate dehydrogenase(LDH) activities than C. Conjugated linoleic acid had no effects on morphometric parameters in C-CLA, as compared to C, but normalized morphometric parameters comparing S-CLA with S. There was a negative correlation between abdominal adiposity and resting metabolic rate. Conjugated linoleic acid effect, enhancing fasting-VO(2)/surface area, postprandial-carbohydrate oxidation and serum lipid hydroperoxide resembled to that of the S group. Conjugated linoleic acid induced cardiac oxidative stress in both fed conditions, and triacylglycerol accumulation in S-CLA rats. Conjugated linoleic acid depressed myocardial LDH comparing C-CLA with C, and beta-hydroxyacyl-coenzyme-A dehydrogenase/CS ratio, comparing S-CLA with S. In conclusion, dietary conjugated linoleic acid supplementation for weight loss can have long-term effects on cardiac health. Conjugated linoleic acid, isomers c9, t11 and t10, c12c9,t11" and "t10,c12" were changed to "c9, t11" and "t10, c12", respectively. Please check if appropriate.--> presented undesirable pro-oxidant effect and induced metabolic changes in cardiac tissue. Nevertheless, despite its effect on abdominal adiposity in sucrose-rich diet condition, conjugated linoleic acid may be disadvantageous because it can lead to oxidative stress and dyslipidemic profile.