Silicon induces phytochelatin and ROS scavengers facilitating cadmium detoxification in rice.

Cadmium (Cd) is detrimental to crops and the environment. This work examines the natural mechanisms underlying silicon- (Si-)directed Cd detoxification in rice plants. The addition of Si to plants under Cd stress caused significant improvements in morphological parameters, chlorophyll score, Fv /Fm and total soluble protein concentration compared to controls, confirming that Si is able to ameliorate Cd-induced damage in rice plants. This morpho-physiological evidence was correlated with decreased cell death and electrolyte leakage after Si application. The results showed no critical changes in root Cd concentration, while shoot Cd decreased significantly after Si supplementation in comparison with Cd-stressed rice. Additionally, expression of Cd transporters (OsNRAMP5 and OsHMA2) was significantly down-regulated while the concentration of phytochelatin, cysteine and glutathione, together with expression of OsPCS1 (phytochelatin synthase) in roots of Cd-stressed rice was significantly induced when subjected to Si treatment. This confirms that the alleviation of Cd stress is not only limited to the down-regulation of Cd transporters but also closely related to the phytochelatin-driven vacuolar storage of Cd in rice roots. The enzymatic analysis further revealed the role of SOD and GR enzymes in protecting rice plants from Cd-induced oxidative harm. These findings suggest a mechanistic basis in rice plants for Si-mediated mitigation of Cd stress.

Effectiveness of circumoral muscle exercises in the developing dentofacial morphology in adenotonsillectomized children: an ultrasonographic evaluation.

Alterations in the functions of the facial muscle can establish changes in facial skeleton and in the development of occlusion. The effect of mouth breathing on the facial morphology is probably greatest during the growth period. Removal of nasal obstruction, adenoids, and tonsils have not given beneficial results in the reversion of the habit unless intercepted with various muscle exercises. Hence, this study was conducted to ultrasonographically evaluate the effectiveness of circumoral muscle exercises in the developing dentofacial morphology in adenotonsillectomized children.

Hypertension as a low-grade systemic inflammatory condition that has its origins in the perinatal period.

Genetics, oxidative stress: superoxide anion (O2*-) and hydrogen peroxide (H2O2), endothelial nitric oxide (eNO), lipid peroxides, anti-oxidants, endothelin, angiotensin converting enzyme (ACE) activity, angiotensinII, transforming growth factor-beta (TGF-beta), insulin, homocysteine, asymmetrical dimethyl arginine, proinflammatory cytokines: interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), C-reactive protein (hs-CRP), and long-chain polyunsaturated fatty acids (LCPUFAs), and activity of NAD(P)H oxidase have a role in human essential hypertension. There is a close interaction between endogenous molecules: eNO, endothelin, cytokines, and nutrients: folic acid, L-arginine, tetrahydrobiopterin (H4B), vitamin B6, vitamin B12, vitamin C, and LCPUFAs. Statins mediate some, if not all, of their actions through LCPUFAs, whereas these fatty acids (especially omega-3 fatty acids) suppress cyclo-oxygenase activity and the synthesis of pro-inflammatory cytokines, and activate parasympathetic nervous system, actions that reduce the risk of major vascular events. Some LCPUFAs form precursors to lipoxins and resolvins that have anti-inflammatory actions. Low-grade systemic inflammation seen in hypertension seems to have its origins in the perinatal period and availability of adequate amounts of LCPUFAs during the critical periods of brain growth prevents the development of hypertension. This indicates that preventive strategies aimed at decreasing the incidence of hypertension and its associated conditions such as atherosclerosis, type 2 diabetes, coronary heart disease (CHD), and cardiac failure in adulthood need to be instituted during the perinatal period if they are to be effective.

Anticonvulsants containing the N-(3-aryl-2-propenoyl) amido pharmacophore.

A series of 1-(3-aryl-2-propenoyl)-4-oxopiperidines (1) as well as some related semicarbazones (2) and thiosemicarbazones (3) were prepared in order to determine whether the relative locations of aryl rings and amidic groups would lead to novel anticonvulsant agents. Initially the compounds were administered intraperitoneally to mice and examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity (NT) screens. The biodata revealed that anticonvulsant properties were displayed by most of the compounds in series (1), in half of the semicarbazones (2) while protection was absent by members of series (3). Molecular modeling was utilized in order to compare the positions of a phenyl ring in relation to amidic groups in representative compounds in series (1-3) with previously reported anticonvulsant agents. Molecular simplification of 4-oxo-1-(3-phenyl-2-propenoyl)piperidine (la) led to 1-(3-phenyl-2-propenoyl)piperidine (7) and N,N-diethylcinnamamide (8) with retention of anticonvulsant properties. Both (la) and (8) afforded protection in the hippocampal kindling screen in rats. When administered orally to rats, (la) and (8) demonstrated activity in the MES screen and in the case of (8), a huge protection index was observed revealing it to be an important lead compound. The IC50 values of all of the compounds towards murine P388 cells were in excess of 50 microM while several compounds displayed cytotoxicity towards Mycobacterium tuberculosis.

Antidiabetic effect of aqueous extract of seed of Tamarindus indica in streptozotocin-induced diabetic rats.

In Indian traditional system of medicine, herbal remedies are prescribed for the treatment of diseases including diabetes mellitus. In recent years, plants are being effectively tried in a variety of pathophysiological states. Tamarindus indica Linn. is one of them. In the present study, aqueous extract of seed of Tamarindus indica Linn. was found to have potent antidiabetogenic activity that reduces blood sugar level in streptozotocin (STZ)-induced diabetic male rat. Supplementation of this aqueous extract by gavage at the dose of 80 mg/0.5 ml distilled water/100 g body weight per day in STZ-induced diabetic rat resulted a significant diminution of fasting blood sugar level after 7 days. Continuous supplementation of this extract for 14 days resulted no significant difference in this parameter from control level. Moreover, this supplementation produced a significant elevation in liver and skeletal muscle glycogen content, activity of liver glucose-6-phosphate dehydrogenase in respect to diabetic group. Activities of liver glucose-6-phosphatase, liver and kidney glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities were decreased significantly in the aqueous extract supplemented group in respect to diabetic group. All these parameters were not resettled to the controlled level after 7 days of this extract supplementation but after 14 days of this supplementation, all the above mentioned parameters were restored to the control level.

Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-beta to prevent human essential hypertension.

Patients with uncontrolled essential hypertension have elevated concentrations of superoxide anion (O(2)(-*)), hydrogen peroxide (H(2)O(2)), lipid peroxides, endothelin, and transforming growth factor-beta (TGF-beta) with a simultaneous decrease in endothelial nitric oxide (eNO), superoxide dismutase (SOD), vitamin E, and long-chain polyunsaturated fatty acids (LCPUFAs). Physiological concentrations of angiotensin II activate NAD(P)H oxidase and trigger free radical generation (especially that of O(2)(-*)). Normally, angiotensin II-induced oxidative stress is abrogated by adequate production and release of eNO, which quenches O(2)(-*) to restore normotension. Angiotensin II also stimulates the production of endothelin and TGF-beta. TGF-beta enhances NO generation, which in turn suppresses TGF-beta production. Thus, NO has a regulatory role on TGF-beta production and is also a physiological antagonist of endothelin. Antihypertensive drugs suppress the production of O(2)(-*) and TGF-beta and enhance eNO synthesis to bring about their beneficial actions. LCPUFAs suppress angiotensin-converting enzyme (ACE) activity, reduce angiotensin II formation, enhance eNO generation, and suppress TGF-beta expression. Perinatal supplementation of LCPUFAs decreases insulin resistance and prevents the development of hypertension in adult life, whereas deficiency of LCPUFAs in the perinatal period results in raised blood pressure later in life. Patients with essential hypertension have low concentrations of various LCPUFAs in their plasma phospholipid fraction. Based on this, it is proposed that LCPUFAs serve as endogenous regulators of ACE activity, O(2)(-*), eNO generation, and TGF-beta expression. Further, LCPUFAs have actions similar to statins, inhibit (especially omega-3 fatty acids) cyclooxygenase activity and suppress the synthesis of proinflammatory cytokines, and activate the parasympathetic nervous system, all actions that reduce the risk of major vascular events. Hence, it is proposed that availability of adequate amounts of LCPUFAs during the critical periods of growth prevents the development of hypertension in adulthood.

Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus. Effect of omega-3 fatty acids.

In a previous study, we showed that prior oral feeding of oils rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid prevent the development of alloxan-induced diabetes mellitus in experimental animals. We also observed that 99% pure omega-6 fatty acids gamma-linolenic acid and arachidonic acid protect against chemically induced diabetes mellitus. Here we report the results of our studies with omega-3 fatty acids. Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. Prior oral supplementation with alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid prevented alloxan-induced diabetes mellitus. alpha-Linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid not only attenuated chemical-induced diabetes mellitus but also restored the anti-oxidant status to normal range in various tissues. These results suggested that omega-3 fatty acids can abrogate chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.

Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus: effect of omega-6 fatty acids.

OBJECTIVE: We previously showed that prior oral supplementation of oils rich in omega-3, eicosapentaenoic acid and docosahexaenoic acid, and omega-6, gamma-linolenic acid and arachidonic acid, can prevent the development of alloxan-induced diabetes mellitus in experimental animals. But the effect of individual fatty acids on chemically induced diabetes mellitus is not known. We report the results of our studies with omega-6 fatty acids. METHODS: Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to linoleic acid, gamma-linolenic acid, and arachidonic acid (AA) but not to dihomo-gamma-linolenic acid. Cyclo-oxygenase and lipoxygenase inhibitors did not block this protective action of AA. Prior oral supplementation with gamma-linolenic acid and pre- and simultaneous treatments with AA prevented alloxan-induced diabetes mellitus. RESULTS: Even though pretreatment with linoleic acid and dihomo-gamma-linolenic acid and simultaneous treatment with linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid did not prevent the development of diabetes mellitus, the severity of diabetes was much less. The saturated fatty acid stearic acid and the monounsaturated fatty acid oleic acid were ineffective in preventing alloxan-induced diabetes mellitus. gamma-Linolenic acid and AA not only attenuated chemically induced diabetes mellitus but also restored the antioxidant status to normal range in various tissues. Changes in the concentrations of various fatty acids of the phospholipid fraction of plasma that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in the AA-treated animals. CONCLUSIONS: These results suggest that polyunsaturated fatty acids can prevent chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.

Can perinatal supplementation of long-chain polyunsaturated fatty acids prevent diabetes mellitus?

It is suggested that the negative correlation between breast-feeding and insulin resistance and diabetes mellitus can be related to the presence of significant amounts of long-chain polyunsaturated fatty acids in the human breast milk. Based on this, it is proposed that provision of adequate amounts of long chain polyunsaturated fatty acids during the critical periods of brain growth and development can prevent or postpone the development diabetes mellitus.

The lipids that matter from infant nutrition to insulin resistance.

Breast-fed infants showed decreased incidence of obesity, hypertension, diabetes mellitus, and coronary heart disease in later life and higher cognitive function. Breast milk is rich in long-chain polyunsaturated fatty acids (LCPUFAs) and brain preferentially accumulates LCPUFAs during the last trimester of pregnancy and the first few months of life. Breast-fed infants showed significantly lower plasma glucose levels and higher percentage of docosahexaenoic acid and total percentages of LCPUFAs in their skeletal muscle biopsies compared with formula fed. LCPUFAs suppress the production of pro-inflammatory cytokines, regulate the function of several neurotransmitters, enhance the number of insulin receptors in the brain and other tissues, and decrease insulin resistance. LCPUFAs may enhance the production of bone morphogenetic proteins (BMPs), which participate in neurogenesis. It is proposed that the beneficial effects of breast feeding in later life can be attributed to its rich LCPUFA content. It is likely that inadequate breast feeding results in marginal deficiency of LCPUFAs during the critical stages of development, which can lead to insulin resistance. Hence, promoting prolonged breast feeding and/or supplementing LCPUFAs during the critical stages of development may be beneficial in preventing insulin resistance.

Can perinatal supplementation of long-chain polyunsaturated fatty acids prevent hypertension in adult life?

It is suggested that adequate provision of long-chain polyunsaturated fatty acids during the critical periods of brain growth prevents the development of hypertension in later life.

Prevention of chemically induced diabetes mellitus in experimental animals by polyunsaturated fatty acids.

Previous studies showed that essential fatty-acid deficiency, conjugated linoleic acid, and a peroxisome proliferator-activated receptor-gamma binding agent such as troglitazone can prevent the development of diabetes mellitus in experimental animals. In the present study, we observed that oral supplementation with oils rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid could protect the animals against alloxan-induced diabetes mellitus. These oils rich in omega-3 and omega-6 fatty acids not only significantly attenuated chemical-induced diabetes mellitus but also restored the antioxidant status to normal range. Changes in the concentrations of different fatty acids shown by the phospholipid fractions of plasma, liver, and muscle tissues that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in these animals. Based on these results and the known mechanisms of alloxan, we suggest that omega-3 and omega-6 long-chain fatty acids can prevent chemically induced diabetes mellitus by enhancing the antioxidant status and suppressing production of cytokines.

Protective action of arachidonic acid against alloxan-induced cytotoxicity and diabetes mellitus.

Previous studies showed that essential fatty acid (EFA) deficiency, conjugated linoleic acid and troglitazone exert a protective effect in animal models of diabetes mellitus. Here we show that alloxan-induced in vitro cytotoxicity and apoptosis in an insulin secreting rat insulinoma, RIN, cells can be prevented by arachidonic acid (AA) and that both cyclo-oxygenase and lipoxygenase inhibitors do not block this protective action. Alloxan-induced diabetes in male Wistar rats was also prevented by oral supplementation of AA, gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This protective action is best when the animals were pre-treated with the fatty acid. These results suggest that polyunsaturated fatty acids can prevent alloxan-induced diabetes mellitus in experimental animals and may be useful to prevent diabetes mellitus in the high-risk population.

Effect of polyunsaturated fatty acids on dexamethasone-induced gastric mucosal damage.

BACKGROUND: Increased dietary intake of polyunsaturated fatty acids (PUFAs) is known to be associated with a decrease in the incidence of peptic ulcer disease possibly due to increase in the synthesis of prostaglandins. But, it is also likely that conversion of PUFAs to PGs may not always be required for gastric mucosal protection. Present study was designed to study the role of PUFAs in pathobiology of steroid induce gastric damage in rats. METHODS: Wistar rats were treated with 5 mg/kg bodyweight of dexamethasone to induce gastric mucosal ulcers. Effects of PUFAs was studied by supplementation of Fish oil (rich in n-3 EPA and DHA) and AA rich oil. Famotidine was used as a positive control. Generation of lipid peroxides, nitric oxide and the activity of anti-oxidant enzymes were also studied. RESULTS: Dexamethasone induced ulceration was associated with changes in the phospholipid fatty acid profile, levels of lipid peroxidation products, nitric oxide and activity of anti-oxidant enzymes. The fatty acid profile showed an increase in LA and a decrease in other PUFAs like GLA, AA, EPA and DHA. When PUFAs were supplemented in the form of Fish oil and AA rich oil or when the animals were treated with H2-blocker, famotidine, there was a decrease in the incidence of ulceration in the animals associated with near normalization of changes in the phospholipid fatty acid profile. The levels of lipid peroxides, nitric oxide, and anti-oxidant activity also reverted to control values. CONCLUSIONS: Dexamethasone induced gastric ulceration was prevented by PUFAs. This is supported by the results of our earlier study where in it was noted that in patients with DU plasma lipid peroxides, nitric oxide and phospholipid fatty acid pattern and red cell antioxidant activity were altered similar to those seen in dexamethasone treated group of the present study. These abnormalities, similar to the PUFA treated groups of the present study, reverted to normalcy following treatment of the patients with lansoprazole, a proton pump inhibitor. Further, PUFAs are known to inhibit the growth of Helicobacter pylori in vitro. Hence, it is concluded that PUFAs, free radicals, nitric oxide and anti-oxidants play a significant role in the pathobiology of peptic ulcer.

Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how?

Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil. Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. One attractive suggestion is a direct cardiac effect of n-3 fatty acids on arrhythmogenesis. N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-induced ventricular fibrillation and sudden cardiac death. Though this is an attractive explanation, there could be other actions as well. N-3 fatty acids can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNFalpha) and interleukin-1 (IL-1) and IL-2 that are released during the early course of ischemic heart disease. These cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardial function. Further, n-3 fatty acids can increase parasympathetic tone leading to an increase in heart rate variability and thus, protect the myocardium against ventricular arrhythmias. Increased parasympathetic tone and acetylcholine, the principle vagal neurotransmitter, significantly attenuate the release of TNF, IL-1beta, IL-6 and IL-18. Exercise enhances parasympathetic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascular diseases and diabetes mellitus. TNFalpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fatty acids. Based on this, it is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter. Thus, there appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids. This may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.

Effect of melatonin on two stage skin carcinogenesis in Swiss mice.

Melatonin, a hormone secreted by the pineal gland, is known to have anti-mutagenic and oncostatic actions. This beneficial action of melatonin has been explained in terms of its ability to scavenge free radicals and augment the activities of anti-oxidant enzymes. In the present study, we evaluated the effect of melatonin on benzo(a)pyrene-induced two stage skin carcinogenesis in mice and observed that it can not only decrease the number of animals bearing papillomas but also the number of papillomas per animal both in the initiation and promotion stages of skin carcinogenesis. It was also found that melatonin treated animals have low levels of lipid peroxides and that it can also prevent the binding of BP or its metabolites to DNA. In view of these evidence, it can be suggested that melatonin may function as an endogenous anti-mutagenic and oncostatic agent.

Effect of evening primrose and fish oils on two stage skin carcinogenesis in mice.

The effect of fish oil (FO, given in the form of MaxEPA) rich in n-3 fatty acids and evening primrose oil (EPO) rich in n-6 fatty acids on two-stage skin carcinogenesis in mice was studied. Both FO and EPO inhibited the papilloma formation to a significant degree only during the promotion stage which was associated with an increase in lipid peroxidation. Both FO and EPO inhibited the binding of benzo(a)-pyrene to skin cell DNA suggesting that this could be one of the mechanism(s) by which these oils could be preventing papilloma development. Neither EPO nor FO influenced epidermal cell proliferation. In the FO group, LA (linoleic acid), AA (arachidonic acid) and DHA (docosahexaenoic acid) were increased, whereas in the EPO group a significant increase in the AA content was noted. No specific changes in the fatty acid pattern were observed in any of the groups that could be attributed to the papilloma incidence. These results suggest that FO and EPO can influence papilloma formation which can be attributed, at least in part, to their ability to prevent benzo(a)pyrene binding to DNA and to an increase the lipid peroxidation process.

Oxidant stress, anti-oxidants and essential fatty acids in systemic lupus erythematosus.

Eicosapentaenoic acid and docosahexaenoic acid (EPA and DHA respectively) can suppress the production of interleukin-1 (IL-1), IL-2 and TNF (tumor necrosis factor) but not of IL-4 by human lymphocytes in vitro. In addition, the concentrations of EPA and DHA were also found to be low in the plasma phospholipid fraction of patients with SLE. In a limited clinical study performed by us earlier, it was observed that oral supplementation of EPA/DHA to patients with SLE can induce clinical remission without any side-effects. Since oxygen free radicals are known to be involved in the pathobiology of SLE, we estimated the plasma concentrations of lipid peroxides, nitric oxide, and anti-oxidants such as catalase, superoxide dismutase (SOD), glutathione peroxidase and vitamin E in these patients both before and after the induction of remission following EPA/DHA administration. These results showed that the levels of lipid peroxides are elevated and those of nitric oxide, SOD and glutathione peroxidase are decreased in SLE prior to EPA/DHA supplementation. Following EPA/DHA administration the concentrations of lipid peroxides, and those of nitric oxide, SOD and glutathione peroxidase reverted to near normal levels. These results suggest that oxidant stress, nitric oxide, and anti-oxidants play a significant role in SLE and that EPA/DHA can modulate oxidant stress and nitric oxide synthesis and may have a regulator role in the synthesis of anti-oxidant enzymes such as SOD and glutathione peroxidase. From the results of this study, we would like to suggest that measurement of lipid peroxides, nitric oxide and anti-oxidants can be used as markers to predict prognosis in patients with SLE.

Effect of free fatty acids on two-stage skin carcinogenesis in mice.

The effect of n-3 and n-6 free fatty acids on two stage skin carcinogenesis in mice was studied. Stearic, linoleic, arachidonic, and eicosapentaenoic acids inhibited both initiation and promotion stages of skin carcinogenesis. Although no direct correlation between lipid peroxidation and papilloma formation was observed, a trend towards an increase in the formation of lipid peroxides with the inhibitory effect of fatty acids on papilloma development was noted. In general, the fatty acids applied were incorporated mainly into the phospholipid and free fatty acid pools. All the fatty acids tested, except eicosapentaenoic and docosahexaenoic acids, inhibited the binding of benzo[a]pyrene (BP) to DNA. On the other hand, BP and croton oil-induced skin cell proliferation was not influenced by any of the fatty acids used. In conclusion, the results of the present study suggest that inhibition of papilloma formation by free fatty acids is complex and can be attributed to a limited extent only to their ability to inhibit BP binding to DNA, to block cell proliferation and enhance the lipid peroxidation process.