Dietary n-3 but not n-6 fatty acids modulate anthropometry and fertility indices in high-fat diet fed rats: a two-generation study.

The present study assessed the modulatory potentials of dietary n-3 [α-linolenic acid (ALA, 18:3n-3, eicosapentaenoic acid (EPA, 20:5n-3 + docosahexaenoic acid (DHA) 22:6n-3), and n-6 fatty acid (LA, 18:2n-6)] on anthropometric parameters and fertility indices in high-fat-fed rats. Weanling female Wistar rats were fed with control diet (7% lard), high-fat diet (35% lard, HFL), high-fat with fish oil (21% fish oil + 14% lard, HFF), high-fat with canola oil (21% canola oil + 14% lard, HFC) and high-fat with sunflower oil (21% sunflower oil + 14% lard, HFS) for 2 months, mated and continued on their diets during pregnancy. At gestation day 18-20, the intra-uterine environment was examined in representative rats, and the rest were allowed for delivering pups. The pups after lactation were subjected to mating and feeding trials as above. Growth parameters (body weight, body length (BL), abdominal circumference (AC), thoracic circumference (TC), and Lee index and fertility parameters (litter size and sex ratio) were studied. Feeding HFL diet increased BL (16%), AC (33%) and TC (21%) compared to control (p < 0.05). Adipose tissue accumulation was 11% higher in the HFL group compared to control and was lowered with n-3 fatty acid incorporation in the diet. HFL group exhibited a lower percentage of fertility, pregnancy, and delivery indices. Litter size was decreased by 20%, and litter weight was increased by 23% in HFL group compared to control with more male pups. Our study indicated that n-3 to a larger extent than n-6 fatty acids modulated high-fat induced changes in the anthropometric parameters and fertility indices.

Ginger and turmeric lipid-solubles attenuate heated oil-induced hepatic inflammation via the downregulation of NF-kB in rats.

PURPOSE: Reusing deep-fried vegetable oils multiple times is a common practice to save costs, and their chronic consumption may cause hepatic dysfunction. In this investigation, we assessed the modulatory effects of ginger and turmeric lipid-solubles that may migrate to oils during heating on the hepatic inflammatory response in rats. METHODS: Male Wistar rats were fed with; 1) control {native canola (N-CNO) or native sunflower (N-SFO)} oil, 2) heated (heated canola {(H-CNO) or heated sunflower (H-SFO)} oil, and 3) heated oil with ginger or turmeric {heated canola with ginger (H-CNO + GI) or heated canola oil with turmeric (H-CNO + TU), heated sunflower oil with ginger (H-SFO + GI) or heated sunflower oil with turmeric (H-SFO + TU)} for 120 days. Hepatic inflammatory response comprising eicosanoids, cytokines, and NF-kB were assessed. RESULTS: Compared to respective controls, feeding heated oils significantly (p < 0.05); 1) increased eicosanoids (PGE2, LTB4, and LTC4) and cytokines (TNF-α, MCP-1, IL-1ß, and IL-6), 2) increased nuclear translocation of NF-kB in the liver, and 3) increased the hepatic expression of 5-LOX, COX-2, BLT-1, and EP-4. However, feeding oils heated with ginger or turmeric positively countered the changes induced by consumption of heated oils. CONCLUSIONS: Consumption of repeatedly heated oil may cause hepatic dysfunction by inducing inflammatory stress through NF-kB upregulation. Lipid-solubles from ginger and turmeric that may migrate to oil during heating prevent the hepatic inflammatory response triggered by heated oils in rats.

Ginger and turmeric lipid-solubles attenuate heated oil-induced cardio-hepatic oxidative stress via the up-regulation of nuclear factor erythroid 2-related factor 2 and decrease blood pressure in rats.

Deep-fried vegetable oils are reused multiple times to save costs, and their chronic consumption may cause organ dysfunction. In this study, we assessed the modulatory effects of lipid-solubles from ginger and turmeric that may migrate to oils during heating, on the cardio-hepatic antioxidant defence response and blood pressure in rats. Male Wistar rats were fed with: (1) control (native rapeseed (N-CNO) or native sunflower (N-SFO)) oil, (2) heated (heated rapeseed (H-CNO) or heated sunflower (H-SFO)) oil and (3) heated oil with ginger or turmeric (heated rapeseed oil with ginger (H-CNO + GI) or heated rapeseed oil with turmeric (H-CNO + TU), heated sunflower oil with ginger (H-SFO + GI) or heated sunflower oil with turmeric (H-SFO + TU)) for 120 d. Oxidative stress (OS) markers, antioxidant enzymes, nitric oxide synthase-2 (NOS-2), intercellular adhesion molecule-1 (ICAM-1), nuclear factor erythroid 2-related factor 2 (NRF-2), markers of hepatic and cardiac function and blood pressure were assessed. Feeding heated oils (H-CNO or H-SFO) (1) increased OS markers, NOS-2 and ICAM-1 expression; (2) decreased antioxidant enzyme activity and NRF-2 level; (3) increased marker enzymes of hepatic and cardiac function and (4) increased systolic and diastolic blood pressure significantly (P < 0·05), when compared with respective native oils (N-CNO or N-SFO). However, feeding oils heated with ginger or turmeric positively countered the changes induced by heated oils. Consumption of repeatedly heated oil causes cardio-hepatic dysfunction by inducing OS through NRF-2 down-regulation. Lipid-solubles from ginger and turmeric that may migrate to oil during heating prevent the oxidative stress and blood pressure triggered by heated oils in rats.

Hyperlipidemia Downregulate Brain Antioxidant Defense Enzymes and Neurotrophins in Rats: Assessment of the Modulatory Potential of EPA+DHA and Zerumbone.

BACKGROUND: Oxidative stress (OS) plays a vital role in the pathogenesis of cognitive disorders. In this study, brain antioxidant defense dysregulation as a consequence of hyperlipidemia, and the efficacy of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), and zerumbone (Z) in their modulation are assessed. METHODS AND RESULTS: Male Wistar rats are fed control, high-fat (HF), HF + fish oil (HF+F), HF + zerumbone (HF+Z), and HF + fish oil + zerumbone (HF+F+Z) diet for 60 days. Markers of OS, antioxidant enzymes, monoamine oxidase, nuclear factor (erythroid-derived 2)-like 2 (NRF-2), nitric oxide-2 (NOS-2), inter cellular adhesion molecule-1 (ICAM-1), and neurotrophins are measured. Hyperlipidemia increases OS, decreases antioxidant enzyme activity, increases monoamine oxidase activity, increases NOS-2 and ICAM-1 expression, decreases NRF-2 activation, decreases nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels in the brain compared to control. While EPA+DHA and zerumbone significantly (p < 0.05) restores the perturbations induced by hyperlipidemia. CONCLUSION: It is concluded that hyperlipidemia cause OS by decreasing the activity of brain antioxidant enzymes via the downregulation of NRF-2. The reduced brain neurotrophins in hyperlipidemia indicate its potential risk on cognitive attributes. EPA+DHA, together with zerumbone, positively modulates hyperlipidemia induced brain dysfunction thereby offering promising therapeutic strategy.

Zerumbone augments cognitive enhancement potentials of EPA+DHA: insight from a hyperlipidaemic rat model.

Hyperlipidaemia and cognitive dysfunction (CD) are the two public health concerns. Though hyperlipidaemia has been comprehensively studied in respect to CVD, its role on CD needs to be explored. Hence, we evaluated hyperlipidaemia as a risk factor for CD and the efficacy of EPA (20 : 5n-3) + DHA (22 : 6n-3) and zerumbone (Z) in modulating CD under hyperlipidaemic conditions. Male Wistar rats (Rattus norvegicus) were fed control, high-fat (HF), high-fat + fish oil (HF + F), high-fat + zerumbone (HF+Z) and high-fat + fish oil + zerumbone (HF+F+Z) containing diets. After a 30 d feeding trial, memory parameters (Morris water maze, elevated plus maze (transfer latency) and T-maze (spontaneous alteration)) and locomotor skills (open field test and rotarod test) were assessed. Hyperlipidaemia significantly (P < 0·05) reduced memory and motor coordination skills compared with control. However, the administration of EPA + DHA and zerumbone significantly (P < 0·05) restored the hyperlipidaemia-induced loss of memory and motor coordination skills. Collectively, our data imply that hyperlipidaemia causes CD by decreasing memory and motor coordination skills, and administration of EPA + DHA and zerumbone prevents hyperlipidaemia-induced CD. The augmented effect of EPA + DHA, together with zerumbone, discloses a promising strategy for lowering the severity of CD in hyperlipidaemic conditions.

Cysteinyl leukotriene receptor antagonism: a promising pharmacological strategy for lowering the severity of arthritis.

BACKGROUND AND AIMS: Though cyclooxygenase inhibitors are employed in rheumatoid arthritis treatment, modulators of leukotrienes are underexplored. We investigated the therapeutic potential of montelukast, a known cysteinyl leukotriene receptor-1 (CysLT1) inhibitor in an experimental rat model of arthritis. METHODS: Arthritis was induced in rats, and montelukast (5 mg/kg body wt.) was administered prophylactically (PAM) and therapeutically (TAM) through oral route. RESULTS AND DISCUSSION: Blood and joint tissue markers of oxidative stress (lipid peroxidation, protein carbonyls, and nitric oxides) were significantly (p < 0.05) reduced in montelukast administered rats. Paw inflammation, RA markers (RF and CRP), eicosanoids (PGE2, LTB4, and LTC4), cytokines (IL-1ß and MCP-1), activity of hydrolytic enzymes (collagenase, elastase, and hyaluronidase), expression of matrix metalloproteinases (MMP), and EP-4 receptor were significantly (p < 0.05) reduced in montelukast administered rats. This study established that leukotriene inhibition through montelukast lowered the severity of arthritis and thus a potential strategy for reducing the severity of arthritis.

Prophylactic effects of probiotic Bifidobacterium spp. in the resolution of inflammation in arthritic rats.

In the present study, the modulatory effects of bifidobacterial spp. (Bifidobacterium breve NCIM 5671, Bifidobacterium longum NCIM 5672 and Bifidobacterium bifidum NCIM 5697) on adjuvant induced arthritis in rats were evaluated. Arthritis was induced in male Wistar rats by injecting 250 µg of Freund's adjuvant directly into the paw. Fifteen days before and 15 days after the induction of arthritis, suspended cultures of bifidobacteria (109 cfu/ml) were administered by oral gavage. Paw volume, bone mineral content, oxidative stress markers, antioxidant enzymes, cytokines, eicosanoids and expression of COX2, as well as bone hydrolytic enzymes, were assessed by RT PCR. Although piroxicam-treated groups (drug control) had better effects than bifidobacteria-treated groups, bifidobacteria probiotics administration exhibited significant (P < 0.05) prophylactic effects in terms of downregulating arthritis markers. Parameters including paw volume, bone mineral content, cytokines, and eicosanoids level were significantly (p < 0.05) modulated in bifidobacteria administered groups compared to arthritic control group. Among the three strains tested, B. breve NCIM 5671 exhibited superior prophylactic effects as assessed in the experimental rat model of arthritis. In conclusion, bifidobacteria probiotics administration can downregulate the markers of arthritis and hence can be a potential therapeutic regimen in the treatment of arthritis.

Aging and Hyperglycemia Intensify Dyslipidemia-Induced Oxidative Stress and Inflammation in Rats: Assessment of Restorative Potentials of ALA and EPA + DHA.

Effect of aging and hyperglycemia on oxidative stress (OS) and inflammation in dyslipidemic conditions has not been elucidated. Hence, in this study, we assessed the implications of aging, hyperglycemia, and also the dietary effect of n-3 fatty acids (α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)) on OS and inflammation in dyslipidemic rats. Dyslipidemia was induced in young and aged rats by feeding high-fat lard (HFL) diet. Diabetes was induced in young dyslipidemic rats by administering streptozotocin 30 days after the induction of dyslipidemia. Experimental groups received diets containing canola oil (HF + CNO) and fish oil (HF + FO) as a source of ALA and EPA + DHA respectively. After 60 days of feeding rats with their respective diets, OS and inflammatory markers in serum were assessed. Dyslipidemia caused significant (p < 0.05) increase in OS (lipid peroxidation, nitric oxide, and protein carbonyl), pro-inflammatory cytokine (CRP, IL-1ß, MCP-1, and TNF-α), and eicosanoid (PGE2, LTB4, and LTC4) level in serum of both young and aged rats. Aged dyslipidemic rats presented significantly (p < 0.05) higher level of these markers compared to young dyslipidemic rats. Hyperglycemia onset further augmented OS and inflammatory markers in young dyslipidemic rats significantly (p < 0.05). Administration of n-3 fatty acids downregulated the serum markers of OS and inflammation in all the three experimental models. Thus, aging and hyperglycemia onset intensified dyslipidemia-induced OS and inflammation. Dietary preformed EPA + DHA presented larger restorative potentials than precursor ALA in countering OS and inflammation in all the three experimental models.

Dietary Unsaturated Fatty Acids Modulate Maternal Dyslipidemia-Induced DNA Methylation and Histone Acetylation in Placenta and Fetal Liver in Rats.

The present study assessed the role of dietary unsaturated fatty acids in maternal dyslipidemia-induced DNA methylation and histone acetylation in placenta and fetal liver and accumulation of lipids in the fetal liver. Weanling female Wistar rats were fed control and experimental diets for 2 months, mated, and continued on their diets during pregnancy. At gestation days of 18-20, rats were euthanized to isolate placenta and fetal liver. DNA methylation, DNA methyl transferase-1 (DNMT1) activity, acetylation of histones (H2A and H2B), and histone acyl transferase (HAT) activity were evaluated in placenta and fetal liver. Fetal liver lipid accumulation and activation of peroxisome proliferator-activated receptor-α (PPAR-α) were assessed. Maternal dyslipidemia caused significant epigenetic changes in placenta and fetal liver. In the placenta, (1) global DNA methylation increased by 37% and DNMT1 activity by 86%, (2) acetylated H2A and H2B levels decreased by 46% and 24% respectively, and (3) HAT activity decreased by 39%. In fetal liver, (1) global DNA methylation increased by 52% and DNMT1 activity by 78%, (2) acetylated H2A and H2B levels decreased by 28% and 26% respectively, and (3) HAT activity decreased by 37%. Maternal dyslipidemia caused a 4.75-fold increase in fetal liver triacylglycerol accumulation with a 78% decrease in DNA-binding ability of PPAR-α. Incorporation of dietary unsaturated fatty acids in the maternal high-fat diet significantly (p < 0.05) modulated dyslipidemia-induced effects in placenta and fetal liver. Eicosapentaenoic acid (EPA, 20:5n-3) + docosahexaenoic acid (DHA, 22:6n-3) exhibited a profound effect followed by alpha-linolenic acid (ALA, 18:3n-3) than linoleic acid (LNA, 18:2n-6) in modulating the epigenetic parameters in placenta and fetal liver.

Sesame Oil and Rice Bran Oil Ameliorates Adjuvant-Induced Arthritis in Rats: Distinguishing the Role of Minor Components and Fatty Acids.

Though present in small amounts, the minor constituents of dietary oils may supplement the dietary therapies for rheumatoid arthritis (RA). Hence, in the present study, we assessed the effect of minor constituents from sesame oil (SO) and rice bran oil (RBO) and their fatty acids on the severity of adjuvant-induced arthritis in experimental rats. Rats were gavaged with 1 mL of SO or RBO or groundnut oil (GNO, control) with or without its minor components for a period 15 days before and 15 days after the induction of arthritis. Oxidative stress, markers of RA, eicosanoids, cytokines, paw swelling and joint integrity were measured in experimental and control rats. Results demonstrated that native SO and RBO but not SO and RBO stripped of their minor components decreased severity of paw inflammation, oxidative stress (lipid peroxides, protein carbonyls, nitric oxide), RA markers (RF and CRP), inflammatory eicosanoids (PGE2, LTB4 and LTC4) and cytokines (IL-1ß, IL-6, MCP-1 and TNF-α) compared to control rats. Native SO and RBO inhibited hydrolytic enzymes (collagenase, elastase and hyaluronidase) in the synovial tissue compared to SO and RBO without minor components. The arthritic scores assessed based on the digital and X-ray images indicated that native oils but not those without their minor components reduced the paw swelling and bone loss. Our results indicated that minor components of SO and RBO possess a significant degree of an anti-arthritic effect and are responsible for down regulating inflammation in the experimentally induced arthritis in rats.

Dietary omega-3 but not omega-6 fatty acids down-regulate maternal dyslipidemia induced oxidative stress: A three generation study in rats.

BACKGROUND: Maternal nutrition modulates fetal metabolic programming and development later. Maternal dyslipidemia effects on oxidative stress (OS) in offsprings and its modulation by dietary fatty acids over generations remains to be elucidated. The objective of present study was to assess the long-term (three generations) effect of omega-3 fatty acids on OS under dyslipidemia. METHODS: Weanling female Wistar rats were fed with control diet (7% lard), high fat diet (35% lard, HFL), high fat with fish oil (21% fish oil + 14% lard, HFF), high fat with canola oil (21% canola oil + 14% lard, HFC) and high fat with sunflower oil (21% sunflower oil + 14% lard, HFS). Following 60 days feeding, the female rats were mated with sexually matured males (fed normal chow diet) and continued with the above diet regimen during pregnancy and lactation. The pups after lactation were continued with their maternal diet for 60 days and subjected to mating and feeding trial as above for two generations. Serum lipid profiles, OS markers (lipid peroxidation, nitric oxide release and protein carbonyl) and antioxidant defence enzymes (catalase, SOD, glutathione peroxidase and glutathione transferase) were assessed in serum, liver and uterus of rats fed on experimental and control diets for three generations. RESULTS: Feeding HFL diet increased blood lipids, OS and lowered the antioxidant enzymes activity in serum, liver and uterus (p < 0.05). The reduction in the antioxidant enzymes in HFL group were higher in third followed by second generation compared to first generation (p < 0.05). Omega-3 fatty acids prevented the dyslipidemia induced loss of antioxidant enzyme activities in serum, liver and uterus. CONCLUSIONS: Our data show for the first time that offsprings born to dyslipidemic mothers' exhibit diminished enzymatic antioxidant defence and its progressive reduction in future generation, and dietary omega-3 fatty acids restore the enzymatic antioxidant defence in offsprings and suppress the markers of OS.