Sudipta Pal

Possible Beneficial Effects of Melatonin Supplementation on Arsenic-Induced Oxidative Stress in Wistar Rats

The effects of melatonin on arsenic-induced changes on cellular antioxidant system were studied in male rats of the Wistar strain. Arsenic treatment (i.p. as sodium arsenite) was done at a dose of 5.55 mg/kg body weight (equivalent to 35% of LD50) per day for a period of 30 days, while melatonin supplementation (i.p.) was performed at a dose of 10 mg/kg body weight per day for the last 5 days prior to sacrifice. Melatonin supplementation reversed the arsenic-mediated changes in reduced glutathione (GSH) level and lipid peroxidation in liver and kidney. Arsenic-induced decreased glutathione reductase activity in liver and increased activity in kidney was appreciably counteracted by melatonin. Melatonin also inhibited arsenic-induced free hydroxyl radical production in the tissues. The decreased superoxide dismutase (SOD) activity in liver and kidney and that of catalase in liver due to arsenic treatment were also counteracted by melatonin. It is suggested that melatonin acts as a protective agent against arsenic-induced cellular oxidative stress.

Ameliorative effects of oleanolic acid on fluoride induced metabolic and oxidative dysfunctions in rat brain: Experimental and biochemical studies

Beneficial effects of oleanolic acid on fluoride-induced oxidative stress and certain metabolic dysfunctions were studied in four regions of rat brain. Male Wistar rats were treated with sodium fluoride at a dose of 20 mg/kg b.w./day (orally) for 30 days. Results indicate marked reduction in acidic, basic and neutral protein contents due to fluoride toxicity in cerebrum, cerebellum, pons and medulla. DNA, RNA contents significantly decreased in those regions after fluoride exposure. Activities of proteolytic enzymes (such as cathepsin, trypsin and pronase) were inhibited by fluoride, whereas transaminase enzyme (GOT and GPT) activities increased significantly in brain tissue. Fluoride appreciably elevated brain malondialdehyde level, free amino acid nitrogen, NO content and free OH radical generation. Additionally, fluoride perturbed GSH content and markedly reduced SOD, GPx, GR and CAT activities in brain tissues. Oral supplementation of oleanolic acid (a plant triterpenoid), at a dose of 5mg/kgb.w./day for last 14 days of fluoride treatment appreciably ameliorated fluoride-induced alteration of brain metabolic functions. Appreciable counteractive effects of oleanolic acid against fluoride-induced changes in protein and nucleic acid contents, proteolytic enzyme activities and other oxidative stress parameters indicate that oleanolic acid has potential antioxidative effects against fluoride-induced oxidative brain damage.

Protective Effect of N‐Acetylcysteine Against Arsenic‐Induced Depletion In Vivo of Carbohydrate

N‐acetylcysteine (NAC), a synthetic aminothiol, possesses antioxidative and cytoprotective properties. The present study evaluates the effect of NAC supplementation on arsenic‐induced depletion in vivo of carbohydrates. Arsenic (as sodium arsenite) treatment (i.p.) of male Wistar rats (120–140 g b.w.) at a dose of 5.55 mg/kg body weight (35% of LD50) per day for a period of 30 days produced a significant decrease in blood glucose level (hypoglycemia) and a fall in liver glycogen and pyruvic acid contents. The free amino acid nitrogen content of liver increased while that of kidney decreased after arsenic treatment. Arsenic also enhanced the liver lactate dehydrogenase activity whereas glucose 6‐phosphatase activity in both liver and kidney decreased significantly following arsenic treatment. Transaminase activities in liver and kidney were not significantly altered except the glutamate–pyruvate transaminase activity that was reduced in kidney after arsenic treatment. Oral administration of NAC (163.2 mg/kg/day) for last 7 days of treatment prevented the arsenic‐induced hypoglycemia and glycogenolytic effects to an appreciable extent. There was also recovery of liver pyruvic acid as well as liver and kidney free amino acid nitrogen content after NAC supplementation. Arsenic‐induced alteration of glucose 6‐phosphatase activity in both liver and kidney was also counteracted by NAC. It is suggested that carbohydrate depletion in vivo due to exposure to arsenic can be counteracted by NAC supplementation.

Protective effect of resveratrol on fluoride induced alteration in protein and nucleic acid metabolism, DNA damage and biogenic amines in rat brain

Fluoride, a well-established environmental carcinogen, has been found to cause various neurodegenerative diseases in human. Sub-acute exposure to fluoride at a dose of 20mg/kgb.w./day for 30 days caused significant alteration in pro-oxidant/anti-oxidant status of brain tissue as reflected by perturbation of reduced glutathione content, increased lipid peroxidation, protein carbonylation, nitric oxide and free hydroxyl radical production and decreased activities of antioxidant enzymes. Decreased proteolytic and transaminase enzymes activities, protein and nucleic acid contents and associated DNA damage were observed in the brain of fluoride intoxicated rats. The neurotransmitters dopamine (DA), norepinephrine (NE) and serotonin level was also significantly altered after fluoride exposure. Protective effect of resveratrol on fluoride-induced metabolic and oxidative dysfunctions was evaluated. Resveratrol was found to inhibit changes in metabolic activities restoring antioxidant status, biogenic amine level and structural organization of the brain. Our findings indicated that resveratrol imparted antioxidative role in ameliorating fluoride-induced metabolic and oxidative stress in different regions of the brain.

Dietary protein-carbohydrate ratio: exogenous modulator of immune response with age.

Manipulation of dietary variables is one the most described events to retard the aging process and maintain immune function. The present study deals with the effect of variable dietary protein-carbohydrate ratios (without caloric restriction) on the alteration of immune response of male albino rats at the level of lymphocyte viability, proliferation, cytotoxicity, DNA fragmentation of blood, spleen and thymus and corticosterone levels in plasma and adrenal gland in relation to aging and duration of dietary exposure. Young (3 months) and aged rats (18 months) maintained with control diet [protein (20%)-carbohydrate (68%)] showed age-induced decrease in immune response with an increase in plasma corticosterone level. Consumption of low protein (8%)-high carbohydrate (80%) (LP-HC) diet for short-term period (15 consecutive days) decreased immune response of young rats with little immunopotentiation of aged rats but prolongation of consumption (for 60 consecutive days) of the LP-HC diet potentiated these immunopotentiation effects. High protein (50%)-low carbohydrate (38%) (HP-LC) diet under short-term exposure contrarily showed little immunopotentiation in young with an immunosuppression in aged rats. Prolongation of exposure (for 60 consecutive days) to the HP-LC diet produced similar but more amplified effects in young rats; whereas, in aged rats a pronounced decrease in peripheral immune response with an activation in thymus-dependent immune response was observed under similar conditions. These results thus suggest that diets with variable dietary protein-carbohydrate ratios act as an exogenous modulator of immune response with age and LP-HC diet may be beneficial to slow down/reduce the impairment of immune response in aged individuals.

Ameliorative Effect of Resveratrol Against Fluoride-Induced Alteration of Thyroid Function in Male Wistar Rats

Resveratrol (3,4,5-trihydroxystilbene), a polyphenol and well-known natural antioxidant has been evaluated for its protective effect against fluoride-induced metabolic dysfunctions in rat thyroid gland. Fluoride, the most abundant anions present in groundwater throughout the world, creates a major problem in safe drinking water and causes metabolic, structural, and functional injuries in different organ systems. Sub-acute exposure to sodium fluoride at a dose of 20xa0mg/kg b.w./day orally to rat for 30xa0days induces thyroidal dysfunction including suppressed synthetic machinery of the thyroid gland to produce nucleic acids and thyroid hormones, mainly T3 and T4. Other functional changes are alteration of certain metabolic enzyme activities like Na+-K+-ATPase, thyroid peroxidase, and 5,5′-deiodinase. Structural abnormality of thyroid follicles by fluoride intoxication clearly indicates its thyrotoxic manifestation. Resveratrol supplementation in fluoride-exposed animals appreciably prevented metabolic toxicity caused by fluoride and restored both functional status and ultra-structural organization of the thyroid gland towards normalcy. This study first establishes the therapeutic efficacy of resveratrol as a natural antioxidant in thyroprotection against toxic insult caused by fluoride.

Long-term Exposure of Variable Dietary Protein-to-Carbohydrate Ratio: Effect on Brain Regional Glutamatergic Activity with Age

Glutamatergic activity of hypothalamus and hippocampus of young (3xa0months) male albino rats having normal diet [protein (20%)–carbohydrate (68%)] was increased with the increase of age. Long-term (60 consecutive days) feeding of low protein (8%)–high carbohydrate (80%) diet (LP–HC) increased glutamatergic activity in these brain regions of young rats and decreased that in aged (18xa0months). On the contrary, supplementation of high protein (50%)–low carbohydrate (38%) diet (HP–LC) under similar condition decreased glutamatergic activity in those brain regions of young and increased that in aged brain regions. Thus, prolonged exposure of LP–HC diet may damage young brain; whereas, HP–LC diet under similar condition causes excitotoxicity to aged brain. Therefore, considering the present scenario in relation to metabolism and receptor activity of glutamatergic system, it may be suggested that long-term consumption of LP–HC and HP–LC diets modulate the brain regional glutamatergic activity reversibly with age.

Metabolic adaptability in hexavalent chromium-treated renal tissue: an in vivo study

Abstract Background Hexavalent chromium [Cr(VI)], an environmental pollutant that originates mostly from anthropogenic sources, is a serious threat to human health. After entering into cells, Cr(VI) is capable of producing excessive free radicals and causing tissue damage. The present study aims to reveal the toxic manifestation of Cr(VI) on the metabolic activity of renal tissue. Methods Male Swiss albino mice were treated orally with potassium dichromate (K2Cr2O7) at a dose of 10u2009mg/kg body weight for a period of 30 days. Important tricarboxylic acid (TCA) cycle enzyme activities like isocitrate dehydrogenase, succinate dehydrogenase and malate dehydrogenase, as well as the activities of enzymes involved in oxidative phosphorylation such as Nicotinamide adenine dinucleotide (NADH) dehydrogenase, were measured. Additionally, transaminase and protease (pronase, cathepsin and trypsin) activities, tissue protein and free amino nitrogen were estimated in renal tissue. Glucose-6-phosphatase, glucose-6-phosphate dehydrogenase and alkaline phosphatase activities, as well as lactic acid, pyruvic acid and chromium contents, of kidneys were determined following standard protocols. Kidney histology was performed by hematoxylin and eosin staining. Results Cr(VI) suppresses the rate-limiting enzymes of the TCA cycle and oxidative phosphorylation indicating an inhibition of renal ATP production. It decreases protease activity by eliminating the protein substrates and alters the gluconeogenic pathway. Cr(VI) worsens the normophysiological attributes of renal tissue by enhancing the activity of alkaline phosphatase, pointing towards kidney disease. Histopathological observations confirmed these biochemical results through the presence of chronic tubular nephritis and altered glomerular structure. Cr(VI) retention occurs to a greater extent in renal tissue, which intensifies the toxic manifestation of this pollutant in the kidney. Conclusions Cr(VI) disrupts the metabolic interaction between carbohydrates and proteins in mammalian renal tissue.

Lead (Pb), a threat to protein metabolic efficacy of liver, kidney and muscle in mice

Lead, being the most dangerous natural heavy metal imposes metabolic dysfunction in organ system. However, the effect of lead on protein metabolic efficacy in the liver, kidney and skeletal muscle in mice has not been well studied. The aim of the present study is to establish the metabolic orientation between the liver, kidney and muscle upon sub-acute lead exposure to assess how protein and amino acid metabolisms are affected. Lead acetate was administered by gavage at a dose of 5xa0mg/kgxa0b.w./once daily for 30xa0days. After the treatment, the liver, kidney and muscle were evaluated for biochemical parameters such as proteolytic enzyme activities (trypsin, cathepsin and pronase), tissue protein content (acidic, basic, neutral and total protein), protein carbonyl content, free amino nitrogen as well as tissue and serum transaminase activities. Degradation of total protein was noted in the liver and kidney possibly due to enhanced carbonylation of proteins whereas it was elevated in skeletal muscle. The proteolytic enzyme activity was inhibited in the liver and elevated in the kidney by lead treatment. Muscular cathepsin and trypsin activities decreased but the pronase activity enhanced following lead exposure. Moreover, a marked reduction of transaminase enzyme activities in all the tissues might be due to enzyme leakage from tissue to blood. Significant alteration in amino acid nitrogen in the affected tissue indicates adaptive mechanisms at play in the organ system. Lead is found to be responsible for alteration of tissue protein and amino acids in a toxic fashion and promotes a cooperative mechanism to minimize the metabolic distress imposed by lead.

Dietary variation of protein–carbohydrate: Effect on hypothalamic and hippocampal GABA–glutamate in relation to aging

Abstract Dietary protein variation has been found to alter brain regional neurochemistry with aging. In the present investigation, we studied the effect of short-term treatment of protein–carbohydrate variable diet to rat on hypothalamic and hippocampal γ-amino butyric acid (GABA)–glutamate metabolism with increase of age. Exposure of male albino rats with diet containing normal protein (20%)–normal carbohydrate (68%) increased GABA metabolism and decreased glutamate metabolism in both hypothalamus and hippocampus with the increase of age. GABA–glutamate metabolism of rats having low protein (8%)–high carbohydrate (80%) diet for short-term period (STP), was activated in young age (3 months) and decreased in old age (18 months) in both the brain regions. On the contrary, intake of high protein (50%)–low carbohydrate (38%) diet under similar condition decreased GABA–glutamate metabolism in both hypothalamus and hippocampus of young brain and increased only in hypothalamus of aged brain. In hippocampus of aged brain the same diet decreased glutamate metabolism without changing its GABA metabolism. These results suggest that an age-associated change in GABA–glutamate metabolism depends on the amount of dietary protein and carbohydrate and also on the brain region.