Effect of maternal exposure of fluoride on oxidative stress markers and amelioration by selected antioxidants in developing central nervous system of rats

Fluoride has been implicated as a pathologic mediator of fluorosis. Interestingly neuronal destruction, synaptic injury occurs by a mechanism involving oxidative stress, however, its effects in developmental stages of life, during maternal fluoride exposure and amelioration are not elucidated. In the present study, pregnant Wistar albino rats were exposed to 50 and 150 ppm fluoride in drinking water during gestation and post gestation. After parturition the pups born to the experimental animals were administered daily with selected antioxidants for 21 consecutive days. Fluoride administration substantially enhanced fluoride accumulation, lipid peroxidation and decreased the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione levels in discrete regions of central nervous system. The results significantly (P < 0.05) demonstrated the effect of fluoride through exacerbated oxidative damage and disrupted antioxidant homeostasis, leading to altered neuronal integrity. The administration of antioxidants vitamin E, vitamin C, selenium and zinc produced a promising accost and timely intervention to the aggravated impairment during highly vulnerable early stage of life.     

Pre and Post Natal Exposure of Fluoride Induced Oxidative Macromolecular Alterations in Developing Central Nervous System of Rat and Amelioration by Antioxidants

The effect of fluoride exposure during gestation and post gestation periods were studied to check the status of oxidant, antioxidant and macromolecular changes in CNS and ameliorative role of antioxidants. The pregnant Wistar albino rats were exposed to 50 and 150 ppm fluoride in drinking water and the pups born to them were used for experimentation. After postpartum, the pups were administered daily selected antioxidants through oral gavage. On 21st postnatal day pups were sacrificed and biochemical parameters were assessed. Fluoride exposure substantially increased the activity/levels of fluoride, LPO, protein oxidation, MAO-B, GOT, GPT and decreased protein thiols, RNA and total proteins in discrete regions of CNS. The findings evidenced fluoride induced dyshomeostasis caused on antioxidants, enzymes, macromolecules and governed the pathophysiological events leading to functional loss in a dose dependent manner. The administration of antioxidants remedied the disquiet caused by high fluoride exposure at extreme vulnerable periods of life.     

Effect of Maternal Exposure of Fluoride on Biometals and Oxidative Stress Parameters in Developing CNS of Rat

Excessive intake of essential elements agitates elemental homeostasis resulting in their heterogeneous distribution. Distraction of these elements in central nervous system (CNS) have been demonstrated in many neurological disorders, which are vital in generating free radicals, causing oxidative stress, and contributing to neuronal maladies. The developing CNS is highly vulnerable to environmental agents, including fluoride. Fluorosis is one such disorder ensued from excessive consumption of fluoride containing water and/or foods that poses a greater threat to the life. Present study offers perturbations caused by fluoride toxicity on the level of biometal and antioxidant homeostasis and their interactions. Pregnant Wistar rats were exposed to 100- and 200-ppm fluoride (F⁻) in drinking water and controls with tap water. The pups born to them were used for the study. On 21st postnatal day, the concentration of fluoride, biometals, and oxidative stress markers were determined in discrete regions of CNS. The levels of fluoride, copper, and iron increased whereas manganese and zinc were decreased considerably. Among antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase were decreased and lipid peroxidation was increased with regional alterations. The correlation coefficient values among oxidative stress markers and biometals were either positive or negative and showed less significance during correlation. The results confirm that the fluoride provoked oxidative stress and biometal deformations are synergistic that successively governs the neuronal damage and developing CNS no longer prevents exacerbations of fluoride.     

Protective effect of Ocimum sanctum L after high-dose 131iodine exposure in mice: an in vivo study

Radioprotective effect of aqueous extract of Ocimum sanctum (40 mg/kg body weight, for 15 days) in mice exposed to high-doses (3.7 MBq) of oral 131iodine was investigated by studying the organ weights, lipid peroxidation and antioxidant defense enzymes in various target organs like liver, kidneys, salivary glands and stomach at 24 hr after exposure in adult Swiss mice. The mean weight of the salivary glands showed significant increase after 131iodine administration. 131iodine exposure significantly increased lipid peroxidation in kidneys and salivary glands in comparison to control animals. Pretreatment with O. sanctum in radioiodine exposed group showed significant reduction in lipid peroxidation in both kidneys and salivary glands. In liver, reduced glutathione (GSH) levels showed significant reduction after radioiodine exposure while pretreatment with O. sanctum exhibited less depletion in GSH level even after 131iodine exposure. However, no such changes were observed in stomach. The results indicate the possibility of using aqueous extract of O. sanctum for ameliorating 131Iodine induced damage to the salivary glands.     

Evaluation of Fluoride-Induced Oxidative Stress in Rat Brain: A Multigeneration Study

Multigenerational evaluation was made in rats on exposure to high fluoride (100 and 200 ppm) to assess neurotoxic potential of fluoride in discrete areas of the brain in terms of lipid peroxidation and the activity of antioxidant enzyme system. The rats were given fluoride through drinking water (100 and 200 ppm) and maintained subsequently for three generations. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes viz, catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione level in first-generation rats and these alterations were more pronounced in the subsequent second and third-generation rats in both the doses tested. Decreased feed and water consumption, litter size and organ (brain) somatic index, marginal drop in body growth rate and mortality were observed in all three generations. Decreased antioxidant enzyme activity and increased malondialdehyde levels found in the present study might be related to oxidative damage that occurs variably in discrete regions of the brain. Results of this study can be taken as an index of neurotoxicity in rats exposed to water fluoridation over several generations.     

Prenatal and Lactational Lead Exposure Enhanced Oxidative Stress and Altered Apoptosis Status in Offspring Rats’ Hippocampus

Oxidative stress and apoptosis facilitation in the developing central nervous system (CNS) have been inferred as two mechanisms related to lead’s neurotoxicity, and excessive reactive oxygen species (ROS) can promote oxidative stress and apoptosis facilitation. Few studies systematically investigated the potential relationship among oxidative stress, ROS generation, and apoptosis facilitation after lead exposure in earlier life as a whole. To better understand the adverse effect on the developing central nervous system (CNS) after lead exposure during pregnancy and lactation, the indexes of oxidative stress, apoptosis status, and Bax and Bcl-2 expression of offspring rats’ hippocampus were determined. Pregnant rats were randomly divided into four groups and given free access to drinking water which contained 0 %, 0.05 %, 0.1 %, and 0.2 % Pb(AC)₂ respectively from gestation day 0 to postnatal day 21 (PND21). Results showed that ROS and malondialdehyde level of either PND7 or PND21 pups’ hippocampus were significantly raised; reduced glutathione level and superoxide dismutase activity were obviously decreased following the increase of blood and brain lead level. Similar to apoptotic indexes, Bax/Bcl-2 ratio increased after 0.1 % and 0.2 % Pb(AC)₂ exposure, especially for the pups on PND7. Comparing with cortex, the hippocampus seemed much more sensitive to damage induced by lead. We concluded that the disruption of pro-oxidant and antioxidant balance and apoptosis facilitation could be associated with the mechanisms of neurotoxicity after lead exposure in earlier life.     

Lipid peroxidation and antioxidant systems in the blood of young rats subjected to chronic fluoride toxicity

Wistar albino rats were exposed to 30 or 100 ppm fluoride in drinking water during their fetal, weanling and post-weaning stages of life up to puberty. Extent of lipid peroxidation and response of the antioxidant systems in red blood cells and plasma to prolonged fluoride exposure were assessed in these rats in comparison to the control rats fed with permissible level (0.5 ppm) of fluoride. Rats treated with 100 ppm fluoride showed enhanced lipid peroxidation as evidenced by elevated malondialdehyde (MDA) levels in red blood cells but, 30 ppm fluoride did not cause any appreciable change in RBC MDA level. 30 ppm fluoride-intake resulted in increased levels of total and reduced glutathione in red blood cells and ascorbic acid in plasma while 100 ppm fluoride resulted in decreases in these levels. The activity of RBC glutathione peroxidase was elevated in both the fluoride-treated groups, more pronounced increase was seen with 100 ppm. Reduced to total glutathione ratio in RBC and uric acid levels in plasma decreased in both the groups. RBC superoxide dismutase activity decreased significantly on high-fluoride treatment. These results suggest that long-term high-fluoride intake at the early developing stages of life enhances oxidative stress in the blood, thereby disturbing the antioxidant defense of rats. Increased oxidative stress could be one of the mediating factors in the pathogenesis of toxic manifestations of fluoride.     

Anti-inflammatory,anti-oxidant effect and cytotoxicity of ocimum sanctum intra oral gel for combating periodontal diseases

It is of interest to evaluate the anti-inflammatory, anti-oxidant effect and cytotoxicity of Ocimum sanctum (an Indian herb, Thulsi) intra oral gel in combating periodontal diseases. Hence, 2% of O. sanctum gel was prepared with Carbopol940 soaked in purified water containing 0.2% w/v sodium benzoate overnight. Hydroxy proplyl methyl cellulose (HPMC) solution was mixed with propylene glycol using using tissue homogenizer. Anti-oxidant effect was analyzed using DPPH radical assay and anti-inflammatory effect was assessed using the inhibition of albumin denaturation assay. Ocimum sanctum gel with various dilutions from10 micro litres to 50 micro litres showed exponential increase in percentage of inhibition from 60.9 to 72.2 exhibiting antioxidant activity. The anti-inflammatory effect of Ocimum sanctum gel showed comparatively equivalent effect with standard diclofenac gel with values ranging from 76.6 for 50 micro liters of Ocimum sanctum gel and 89.6 for standard gel at 50 micro liters. Ocimum sanctum showed less toxicity towards brine shrimp nauplii. Thus we show that Ocimum sanctum gel showed potent anti-oxidant and anti-inflammatory effect and less toxic to brine shrimp nauplii as a promising agent for the treatment of periodontal diseases.     

Antioxidant and radioprotective properties of an Ocimum sanctum polysaccharide

The antioxidant activity of two polysaccharides isolated from the Indian medicinal plants, Ocimum sanctum and Tinospora malabarica, was studied. Only the O. sanctum polysaccharide (OSP) showed significant activity. OSP could prevent oxidative damage to liposomal lipids and plasmid DNA induced by various oxidants such as iron, AAPH and gamma-radiation, besides scavenging important ROS such as the superoxide radical and hydrogen peroxide and inhibiting xanthine oxidase. In addition, OSP could prevent gamma-radiation-mediated cell deaths in mouse splenocytes.     

Attenuation of TCDD-induced oxidative stress by 670 nm photobiomodulation in developmental chicken kidney

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent developmental teratogen inducing oxidative stress and sublethal changes in multiple organs, provokes developmental renal injuries. In this study, we investigated TCDD-induced biochemical changes and the therapeutic efficacy of photobiomodulation (670 nm; 4 J/cm(2)) on oxidative stress in chicken kidneys during development. Eggs were injected once prior to incubation with TCDD (2 pg/g or 200 pg/g) or sunflower oil vehicle control. Half of the eggs in each dose group were then treated with red light once per day through embryonic day 20 (E20). Upon hatching at E21, the kidneys were collected and assayed for glutathione peroxidase, glutathione reductase, catalase, superoxide dimutase, and glutathione-S-transferase activities, as well as reduced glutathione and ATP levels, and lipid peroxidation. TCDD exposure alone suppressed the activity of the antioxidant enzymes, increased lipid peroxidation, and depleted available ATP. The biochemical indicators of oxidative and energy stress in the kidney were reversed by daily phototherapy, restoring ATP and glutathione contents and increasing antioxidant enzyme activities to control levels. Photobiomodulation also normalized the level of lipid peroxidation increased by TCDD exposure. The results of this study suggest that 670 nm photobiomodulation may be useful as a noninvasive treatment for renal injury resulting from chemically induced cellular oxidative and energy stress.     

Suppression of Mitochondrial Oxidative Phosphorylation and TCA Enzymes in Discrete Brain Regions of Mice Exposed to High Fluoride: Amelioration by Panax ginseng (Ginseng) and Lagerstroemia speciosa (Banaba) Extracts

Chronic fluoride intoxication results in pathophysiological complications pertaining to soft tissues, called non-skeletal fluorosis. This study examined whether fluoride-induced alterations in selected parameters that are indicative of mitochondrial dysfunction accompany the toxic effects of fluoride in discrete brain regions in vivo and also explored the possibility of treatment with Ginseng (GE) and Banaba (BLE) either alone or with their co-exposure which is capable of reversing parameters indicative of fluoride-induced impairments in mitochondrial function. Swiss mice, Mus musculus, were given 270 ppm fluoride (600 ppm NaF) in their drinking water for 30 days, while continuing the fluoride exposure, toxicated animals were given differential doses (50–250 mg/kg body wt) of phytoextracts through oral gavage for 2 weeks. Discrete brain regions separated from dissected animals to perform biochemical assessments. Disturbances in mitochondrial enzyme complexes (I-IV) and decrements in TCA enzymes (ICDH, SDH, and aconitase) were noted in discrete brain regions upon F exposure, suggesting mitochondrial dysfunction. In addition, a significant reduction in oxidative stress indices with increased MDA content as well as decrease in reduced glutathione content and increases in catalase and SOD enzyme activity suggests the involvement of severe oxidative stress affecting the mitochondrial function(s). Treatment with either GE or BLE reversed F-induced alterations in augmenting the suppressed complex enzymes followed by TCA enzymes and oxidative stress indices in a dose independent manner. However, the co-exposure of GE and BLE at a dose of 150 mg/kgbw appeared to restore mitochondrial functioning. These results provide in vivo evidence supporting the hypothesis that fluoride induces impairments in mitochondrial function, which can be reversed by treatment with GE and BLE as well their co-exposure at 150 mg/kgbw.     

Establishment of drug delivery system nanocapsulated with an antioxidant (+)-catechin hydrate and sodium meta borate chelator against sodium fluoride induced oxidative stress in rats

Oxidative stress a major cause of fluoride induced toxicity and mitochondrial impairment in common in experimental rats during chronic exposure of fluoride. Attempts have been made in the present experiment to diminish oxidative damage, combined therapy with (+)-catechin hydrate (an antioxidant) and sodium meta borate (chelator) were used. Fluoride intoxication in rats was performed by using 13 mg/kg NaF and both antioxidant CH and chelator SMB were used at a concentration of 8.98 μM/kg body weight. Mixture of CH and SMB in free or in PLGA nanocapsule encapsulated form were prepared. The efficacies of those formulations were tested in combating free radical mediated oxidative insult produced by sodium fluoride (NaF). The amalgamated therapy used in this experiment was shown to reduce fluoride levels in liver, brain and kidney from 9.5, 5.5, 6.3 μg/g to 4.6, 2, 2.6 μg/g, respectively. Our result indicated that the combined chelator and antioxidant therapy in nanocapsulated drug delivery system could provide a projection in combating fluoride induced mitochondrial impairment in rat model.     

A possible mechanism for combined arsenic and fluoride induced cellular and DNA damage in mice

Arsenic and fluoride are major contaminants of drinking water. Mechanisms of toxicity following individual exposure to arsenic or fluoride are well known. However, it is not explicit how combined exposure to arsenic and fluoride leads to cellular and/or DNA damage. The present study was planned to assess (i) oxidative stress during combined chronic exposure to arsenic and fluoride in drinking water, (ii) correlation of oxidative stress with cellular and DNA damage and (iii) mechanism of cellular damage using IR spectroscopy. Mice were exposed to arsenic and fluoride (50 ppm) either individually or in combination for 28 weeks. Arsenic or fluoride exposure individually led to a significant increase in reactive oxygen species (ROS) generation and associated oxidative stress in blood, liver and brain. Individual exposure to the two toxicants showed significant depletion of blood glutathione (GSH) and glucose 6-phosphate dehydrogenase (G6PD) activity, and single-stranded DNA damage using a comet assay in lymphocytes. We also observed an increase in the activity of ATPase, thiobarbituric acid reactive substance (TBARS) and a decreased, reduced and oxidized glutathione (GSH?:?GSSG) ratio in the liver and brain. Antioxidant enzymes like superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were decreased and increased in liver and brain respectively. The changes were more pronounced in liver compared to brain suggesting liver to be more susceptible to the toxic effects of arsenic and fluoride. Interestingly, combined exposure to arsenic and fluoride resulted in less pronounced toxic effects compared to their individual effects based on biochemical variables, IR spectra, DNA damage (TUNEL and comet assays) and histopathological observations. IR spectra suggested that arsenic or fluoride perturbs the strength of protein and amide groups; however, the shifts in peaks were not pronounced during combined exposure. These results thus highlight the role of arsenic- or fluoride-induced oxidative stress, DNA damage and protein interaction as the major determinants of toxicity, along with the differential toxic effects during arsenic-fluoride interaction during co-exposure. The study further corroborates our earlier observations that at the higher concentration co-exposures to these toxicants do not elicit synergistic toxicity.     

Antidiabetic, antihypercholesterolaemic and antioxidant effect of Ocimum sanctum (Linn) seed oil

Antihyperlipidaemic and antioxidant effect of Ocimum sanctum Linn. seed oil (OSSO) was investigated in rabbits. Administration of OSSO (0.8 g/kg body weight/day) for four weeks, in cholesterol (100 mg/kg body weight/day) fed rabbits significantly decreased serum cholesterol, triacylglycerol and LDL-+VLDL-cholesterol as compared to untreated cholesterol fed group. There was significant fall in atherogenic index in OSSO treated group. In addition, treatment with OSSO decreased lipid peroxidation and increased reduced glutathione content in blood. Antidiabetic effect of O. sanctum seed oil was evaluated in alloxan diabetic rabbits. Two weeks treatment of diabetic rabbits with OSSO (0.8 gm/kg/day) showed no significant hypoglycaemic effect. Results of the present study show that OSSO has hypocholesterolaemic and antioxidant effects but it does not have antidiabetic effect.     

Role of Endoplasmic Reticulum Stress in Aberrant Activation of Fluoride-Treated Osteoblasts

The aberrant activation of osteoblasts in the early stage is one of the critical steps during the pathogenesis of skeletal fluorosis. The endoplasmic reticulum (ER) stresses and unfolded protein response (UPR) are initiated to alleviate the accumulation of unfolded proteins against cell injury. The previous researches had demonstrated that fluoride induced ER stress in other cells or tissues. In this study, we determined the ER stress and UPR to investigate their roles in aberrant activation of fluoride-treated osteoblasts. The gene expression of bone markers and UPR factors in MC3T3-E1 cells treated with varying doses of fluoride administration was analyzed. Meantime, levels of glutathione and glutathione disulfide were tested by the ultraperformance liquid chromatography–tandem mass spectrometry applications. Our results indicated that a certain dose and period of fluoride administration induced cell proliferation and differentiation, and Runx2 was involved in the regulation of osteoblastic differentiation of MC3T3-E1 cells. Increase trend of Runx2 expression was consistent with change of marker of ER stress. Fluoride caused ER stress and stimulated UPR during the process of osteoblast maturation, while oxidative stress was also active in the occurrence of ER stress. These data indicated that ER stress and UPR were possibly involved in the action of fluoride on osteoblasts.     

Azadirachta indica and Ocimum sanctum leaf extracts alleviate arsenic toxicity by reducing arsenic uptake and improving antioxidant system in rice seedlings

In the present study the potentials of aqueous extracts of the two plants, neem (Azadirachta indica) and Tulsi (Ocimum sanctum) were examined in alleviating arsenic toxicity in rice (Oryza sativa L.) plants grown in hydroponics. Seedlings of rice grown for 8 days in nutrient solution containing 50 μM sodium arsenite showed decline in growth, reduced biomass, altered membrane permeability and increased production of superoxide anion (O2·−), H2O2 and hydroxyl radicals (·OH). Increased lipid peroxidation marked by elevated TBARS (thiobarbituric acid reactive substances) level, increased protein carbonylation, alterated levels of ascorbate, glutathione and increased activities of enzymes SOD (superoxide dismutase), CAT (catalase), APX (ascorbate peroxidase) and GPX (glutathione peroxidase) were noted in the seedlings on As treatment. Exogenously added leaf aqueous extracts of Azadirachta indica (0.75 mg mL−1, w/v) and Ocimum sanctum (0.87 mg mL−1, w/v) in the growth medium considerably alleviated As toxicity effects in the seedlings, marked by reduced As uptake, restoration of membrane integrity, reduced production of ROS, lowering oxidative damage and restoring the levels of ascorbate, glutathione and activity levels of antioxidative enzymes. Arsenic uptake in the seedlings declined by 72.5% in roots and 72.8% in shoots, when A. indica extract was present in the As treatment medium whereas with O. sanctum extract, the uptake declined by 67.2% in roots and 70.01% in shoots. Results suggest that both A. indica and O. sanctum aqueous extracts have potentials to alleviate arsenic toxicity in rice plants and that A. indica can serve as better As toxicity alleviator compared to O. sanctum.     

Lipid peroxidation and antioxidant defence status during larval development and metamorphosis of giant prawn,Macrobrachium rosenbergii

In the present communication we studied the involvement of reactive oxygen species and alteration in antioxidant defence status during larval development and metamorphosis of giant prawn, Macrobrachium rosenbergii. Overall results indicate that there was a decline in endogenous lipid peroxidation level during larval development. Activity of superoxide dismutase was the lowest in early larval stages (Zoea-I and II) and thereafter increased in V and VI stages, followed by a decrease in the subsequent larval stages. Catalase and glutathione peroxidase did not exhibit specific pattern of changes during development. Reduced glutathione content exhibited an incremental increase during larval progression until metamorphosis. Ascorbic acid content of the larval tissue remained unaltered during development but a sharp fall was marked in its content in the post-larvae. Hence it is concluded that early larvae face high oxidative stress as evident from the high content of thiobarbituric acid reactive substances. This may be due to direct exposure of larvae to ambient oxygen of the water as well as their low antioxidant potential. However, during development with the augmentation in antioxidant reserve of the larval tissues a diminution in the oxidative stress was recorded. Thus it is presumed that antioxidant defences play an important role in providing protection to the developing larvae from oxidative assault during larval progression and metamorphosis.     

TCDD-mediated oxidative stress in male rat pups following perinatal exposure

2,3,7,8-tetrachlorododibenzo-p-dioxin (TCDD) is a highly persistent trace environmental contaminant and is one of the most potent toxicants known. Exposure to TCDD has been shown to cause oxidative stress in a variety of animal models. In this study, pregnant Long Evans rats were dosed with 1 microg TCDD/kg on gestational day (GD) 15 so as to investigate oxidative stress in the liver of male pups following gestational exposure to TCDD. Lipid peroxidation (TBARS), production of reactive oxygen species (ROS), and total glutathione (GSH) were assayed to identify changes in oxidative stress parameters in the pup liver at GD 21 and postnatal days (PND) 4, 25, 32, 49, and 63. Mean ROS levels in pups were elevated at all time points tested with a significant elevation at PND 4 and PND 25. However, pup hepatic lipid peroxidation was unchanged throughout the time course. In addition, hepatic total GSH levels were not significantly changed although the means for the TCDD-treated groups were less than those of the controls at all time points except PND 49. The results indicate that although the levels of ROS are increased following gestational/lactational exposure, this increase does not translate to direct oxidative damage or significant changes to endogenous antioxidant defense mechanisms. Further investigation into the effect of gestational/lactational exposure in pups should include additional endpoints for further characterization of the time course of the response, the effect upon extrahepatic tissues, and investigation of differences between male and female offspring.     

Intrauterine exposure to flavonoids modifies antioxidant status at adulthood and decreases oxidative stress-induced DNA damage

Maternal intake of flavonoids, known for their antioxidant properties, may affect the offspring's susceptibility to developing chronic diseases at adult age, especially those related to oxidative stress, via developmental programming. Therefore, we supplemented female mice with the flavonoids genistein and quercetin during gestation, to study their effect on the antioxidant capacity of lung and liver of adult offspring. Maternal intake of quercetin increased the expression of Nrf2 and Sod2 in fetal liver at gestational day 14.5. At adult age, in utero exposure to both flavonoids resulted in the increased expression of several enzymatic antioxidant genes, which was more pronounced in the liver than in the adult lung. Moreover, prenatal genistein exposure induced the nonenzymatic antioxidant capacity in the adult lung, partly by increasing glutathione levels. Prenatal exposure to both flavonoids resulted in significantly lower levels of oxidative stress-induced DNA damage in liver only. Our observations lead to the hypothesis that a preemptive trigger of the antioxidant defense system in utero had a persistent effect on antioxidant capacity and as a result decreased oxidative stress-induced DNA damage in the liver.     

Novel Ocimumoside A and B as anti-stress agents: modulation of brain monoamines and antioxidant systems in chronic unpredictable stress model in rats

Therapies targeting central stress mechanisms are fundamental for the development of successful treatment strategies. Ocimum sanctum (OS) is an Indian medicinal plant traditionally used for the treatment of various stress-related conditions. Previously, we have isolated and characterized three OS compounds; Ocimarin, Ocimumoside A and Ocimumoside B. However, their role in modulating chronic stress-induced central changes is unexplored. Thus, in the present study the efficacy of these OS compounds have been evaluated on the chronic unpredictable stress (CUS)-induced alterations in the monoaminergic and antioxidant systems in the frontal cortex, striatum and hippocampus, along with the changes in the plasma corticosterone levels. CUS (two different types of stressors daily for seven days) resulted in a significant elevation of plasma corticosterone level, which was reversed to control levels by pretreatment with Ocimumoside A and B (40 mg/kg p.o.), while Ocimarin showed no effect. The levels of NA, DA and 5-HT were significantly decreased in all the three brain regions by CUS, with a selective increase of DA metabolites. A significant decrease in the glutathione (GSH) content, the activities of superoxide dismutase and catalase with a significant increase in the glutathione peroxidase activity and lipid peroxidation was observed in all the three regions of the brain by CUS. The OS compounds alone did not cause any significant change in the baseline values of these parameters. However, Ocimumoside A and B (40 mg/kg body p.o.) attenuated these CUS-induced alterations with an efficacy similar to that of standard anti-stress (Panax quinquefolium; 100 mg/kg p.o.) and antioxidant (Melatonin; 20 mg/kg i.p.) drugs. While, Ocimarin failed to modulate these CUS-induced alterations. Therefore, this is the first report which identified the anti-stress activity of novel Ocimumoside A and B at the level of central monoamines and antioxidant properties, implicating their therapeutic importance in the prevention of stress-related disorders.