White tea - A cost effective alternative to EGCG in fight against benzo(a)pyrene (BaP) induced lung toxicity in SD rats.

Tea is a natural resource of catechins and exhibits antioxidative and anticancer activities. This study was designed to elucidate the comparative efficacy of white tea and pure EGCG in containing benzo (a) pyrene (BaP)-induced pulmonary stress. Rats were treated with white tea extract (WT) (1%) and pure EGCG at a dose of 80µg/ml in drinking water on alternate days for 12 weeks (4 weeks prior, during and after BaP treatment). BaP(50 mg/kg b. wt) was administered to rats orally in olive oil twice a week for four weeks. The indices such as stress biomarkers (LPO, PCC & ROS), antioxidant enzymes (SOD, CAT, GSH, GST, GR, GPx) activities and lung histoarchitecture were assessed. BaP administration enhanced the levels of inflammatory markers (NO and citrulline) and reduced activities of antioxidant enzymes. We observed similar antioxidant efficacy by both WT and EGCG as seen by their ameliorative action in restoring BaP induced oxidative and inflammatory stress as well as lung histoarchitecture. Our findings suggest that WT is equally beneficial as EGCG in maintaining the integrity of alveoli and is a potential candidate to be used as a cost effective and protective agent in conditions of BaP-induced lung damage.

Neuro-protective potential of quercetin during chlorpyrifos induced neurotoxicity in rats.

Chlorpyrifos (CPF) has been considered as one of the most potent organophosphates and is linked to several neurological disorders. On the other hand, Quercetin is a vital plant flavanoid and has been reported to regulate a number of physiological processes in the central nervous system. The present study was conducted to investigate the protective potential of quercetin during chlorpyrifos induced neurotoxicity. Female Wistar rats weighing 150-200 g were divided into four different groups viz: Normal control, CPF treated (13.5 mg/kg.b.wt. every alternate day), Quercetin treated (50 mg/kg.b.wt./day) and combined CPF and quercetin-treated. All the treatments were carried out for a total duration of eight weeks. Chlorpyrifos treatment showed significant alterations in the cognitive behavior and motor activities of rats, which were appreciably improved upon simultaneous supplementation with quercetin. Further, CPF treatment caused a significant inhibition in the enzyme activities of acetylcholinesterase and choline acetyltransferase, but caused an increase in the levels of acetylcholine in the brain. Further, chlorpyrifos exposure significantly elevated the levels of lipid peroxidation and protein carbonyl contents as well as the activities of catalase, superoxide dismutase, which were interestingly found to be decreased following co-treatment with quercetin. In contrast, CPF treatment decreased the activities of glutathione reductase, transferase, as well as levels of reduced and total glutathione in both the cerebrum and cerebellum but co-administration of quercetin, increased these levels. Chlorpyrifos treatment altered the neuro-histoarchitecture, which showed improvement upon quercetin supplementation. Hence, this study suggests that quercetin can be used as a prophylactic intervention to prevent CPF induced neurotoxicity.

Evidence of similar protective effects afforded by white tea and its active component 'EGCG' on oxidative-stress mediated hepatic dysfunction during benzo(a)pyrene induced toxicity.

The present study was conducted to unravel the comparative efficacy of White Tea (WT) and Epigallocatechin gallate (EGCG) in affording protection against benzo (a) pyrene (BaP) induced hepatotoxicity. The animals were randomly divided into six groups viz., normal control (NC), BaP, EGCG, WT, WT + BaP and EGCG + BaP treated. 50 mg/kg of BaP was given orally twice a week for 4 weeks. WT extract (1%) and EGCG (1% WT equivalent) were given on alternate days for 12 weeks (4 weeks prior, during and after BaP treatment). BaP treated animals showed a significant increase in the activities of biomarkers in conditions of inflammatory, oxidative and liver stress. However, the levels of these biomarkers were decreased appreciably upon treatment with WT and EGCG. Interestingly, no marked differences in these indices were experienced in animals treated with either EGCG or WT. Further, BaP treatment decreased significantly the amount of endogenous antioxidants which however were increased substantially when WT and EGCG were supplemented to BaP treated animals. BaP induced hepatic histoarchitectural alterations also showed an appreciable improvement when these animals were supplemented with WT or EGCG. The present study thus recommends the usefulness of WT extract vis-a -vis EGCG in mitigating BaP induced hepatic dysfunctions.

Understanding the role of 3-O-Acetyl-11-keto-ß-boswellic acid in conditions of oxidative-stress mediated hepatic dysfunction during benzo(a)pyrene induced toxicity.

The present study was planned to see whether 3-O-Acetyl-11- keto-ß-boswellic acid has any protective effects against benzo(a)pyrene (BaP) induced toxicity or not. In vitro studies show concentration dependent linear association of radical scavenging activity of AK which is comparable to ascorbic acid taken as reference compound. For in vivo studies, the animals were divided randomly into five groups which included a) normal control, b) vehicle treated (olive oil), c) BaP treated, d) AK treated and e) AK + BaP (combined treated). BaP was administered at a dose of 50mg/kg in olive oil twice a week orally for 4 weeks and AK (50mg/kg) was given in olive oil thrice a week for 4 weeks before and after BaP exposure. BaP treated animals showed a significant increase (p < 0.001) in lipid peroxidation (LPO) and protein carbonyl contents (PCC) in hepatic tissue. Further, a significant increase (p < 0.001) in the liver marker enzymes as well as citrulline and nitric oxide levels in the hepatic tissue was also observed. Interestingly, AK when supplemented to BaP treated animals ameliorated the above said biochemical indices appreciately. The histopathological observations also showed appreciable improvement when BaP treated animals were supplemented with AK, thus emphasing the protective potential of AK.

Evidence of Zinc in Affording Protection Against X-Ray-Induced Brain Injury in Rats.

In the present world, X-rays have been regarded as one of the most efficient tools in medicine, industry and research. On the contrary, extensive human exposure to these rays is responsible for causing detrimental effects on physiological system. The aim of the present study was to investigate the role of zinc (Zn), if any, in mitigating the adverse effects induced by fractionated X-irradiation on rat brain. Female Sprague-Dawley rats weighing 170-200 g were divided into four different groups viz.: (a) normal control, (b) X-irradiated (21Gy), (c) zinc treated (227 mg/L in drinking water) and (d) X-irradiated + zinc treated. The skulls of animals belonging to groups (b) and (d) were exposed to X-rays in 30 fractions. Each fraction delivered a radiation dose of 70 rads, and rats were exposed to two fractions every day for 15 days, consecutively. X-ray treatment resulted in significant alterations in the neurobehavior, neurotransmitter levels and neuro-histoarchitecture of rats, whereas zinc co-treatment with X-rays resulted in significant improvement in these parameters. X-ray exposure also caused a significant increase in the levels of lipid peroxidation as well as activities of catalase and superoxide dismutase, which however were decreased upon simultaneous Zn treatment. On the contrary, X-ray treatment down-regulated the glutathione system, which were found to be up-regulated by zinc co-treatment. Further, protein expressions of p53 and NF-ҚB were found to be significantly elevated after X-irradiation, which were reversed following Zn supplementation. Hence, Zn seems to be an effective agent in mitigating the detrimental effects caused by exposure to X-rays.

Zinc Improves Cognitive and Neuronal Dysfunction During Aluminium-Induced Neurodegeneration.

Metals are considered as important components of a physiologically active cell, and imbalance in their levels can lead to various diseased conditions. Aluminium (Al) is an environmental neurotoxicant, which is etiologically related to several neurodegenerative disorders like Alzheimer's, whereas zinc (Zn) is an essential trace element that regulates a large number of metabolic processes in the brain. The objective of the present study was to understand whether Zn provides any physiological protection during Al-induced neurodegeneration. Male Sprague Dawley rats weighing 140-160 g received either aluminium chloride (AlCl3) orally (100 mg/kg b.wt./day), zinc sulphate (ZnSO4) in drinking water (227 mg/L) or combined treatment of aluminium and zinc for 8 weeks. Al treatment resulted in a significant decline in the cognitive behaviour of rats, whereas zinc supplementation caused an improvement in various neurobehavior parameters. Further, Al exposure decreased (p ≤ 0.001) the levels of neurotransmitters, acetylcholinesterase activity, but increased (p ≤ 0.001) the levels of L-citrulline as well as activities of nitric oxide and monoamine oxidase in the brain. However, zinc administration to Al-treated animals increased the levels of neurotransmitters and regulated the altered activities of brain markers. Western blot of tau, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ubiquitin, α-synuclein and Hsp 70 were also found to be elevated after Al exposure, which however were reversed following Zn treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of loss of pyramidal and Purkinje cells, which were improved upon zinc co-administration. Therefore, the present study demonstrates that zinc improves cognitive functions by regulating α-synuclein and APP-mediated molecular pathways during aluminium-induced neurodegeneration.

Role of angiogenic factors of herbal origin in regulation of molecular pathways that control tumor angiogenesis.

The formation of blood capillaries to sustain development and growth of new tissues is referred to as angiogenesis. Angiogenesis is pivotal in both carcinogenesis and metastasis since capillaries are the sole source of supplying nutrients and oxygen to the proliferating tumor cells; therefore, this dependency of tumor growth on angiogenesis challenges researchers to halt tumor growth by targeting angiogenesis with the help of either synthetic or natural inhibitors. Many synthetic inhibitors of angiogenesis have not only come into force but also resulted in some severe adverse effects. Natural compounds may effectively fit into this condition and possibly decrease the time of treatment. In the recent past, literature is replete with evidences advocating the usefulness of natural compounds that target multiple biochemical pathways. The additional advantage of natural compounds is that their active principles interact with one another and work synergistically to give more meaningful and reliable effects than individual principle. Hence, if we are somehow able to combine more than two natural compounds, then it may be possible to enhance their potential by many folds, which shall prove to be very effective in combating tumor angiogenesis. This review shall discuss the concept of angiogenesis, molecular pathways, and angiogenic inhibitors and their specific targets and potential of natural compounds to greatly enhance the current knowledge of angiogenesis-inhibiting factors.

Modulation of (14) C-labeled glucose metabolism by zinc during aluminium induced neurodegeneration.

Aluminium (Al) is one of the most prominent metals in the environment and is responsible for causing several neurological disorders, including Alzheimer's disease. On the other hand, zinc (Zn) is an essential micronutrient that is involved in regulating brain development and function. The present study investigates the protective potential of Zn in the uptake of (14) C-labeled amino acids and glucose and their turnover in rat brain slices during Al intoxication. Male Sprague Dawley rats (140-160 g) were divided into four different groups: normal control, Al treated (100 mg/kg body weight/day via oral gavage), Zn treated (227 mg/liter in drinking water), and Al + Zn treated. Radiorespirometric assay revealed an increase in glucose turnover after Al exposure that was attenuated after Zn treatment. Furthermore, the uptake of (14) C-labeled glucose was increased after Al treatment but was appreciably decreased upon Zn supplementation. In addition, the uptakes of (14) C-lysine, (14) C-leucine, and (14) C-aspartic acid were also found to be elevated following Al exposure but were decreased after Zn treatment. Al treatment also caused alterations in the neurohistoarchitecture of the brain, which were improved after Zn coadministration. Therefore, the present study suggests that Zn provides protection against Al-induced neurotoxicity by regulating glucose and amino acid uptake in rats, indicating that Zn could be a potential candidate for the treatment of various neurodegenerative disorders.

Zinc down regulates Apaf-1-dependent Bax/Bcl-2 mediated caspases activation during aluminium induced neurotoxicity.

Aluminium (Al), a ubiquitous element in nature is associated with the onset of Alzheimer's disease. On the other hand, zinc (Zn) is an essential trace element that regulates large number of physiological processes in the human body. The present study was conducted to explore the role of zinc, if any, in regulating apoptotic machinery during Al induced neurodegeneration in rat. Male sprague dawley rats weighing 140-160 g were divided into four different groups viz: Normal control, Al treated (100 mg/kg b.wt./day), Zn treated (227 mg/l) and combined Al and Zn treated. All the treatments were carried out for a total duration of 8 weeks. Al treatment resulted in a significant increase in the protein expressions of cytochrome c, Bax, Apaf-1, caspase 9, caspase 3 (p17), caspase 8, caspase 6, caspase 7 but decreased the Bcl-2 in both the cerebrum and cerebellum. However, Zn supplementation to Al treated rats resulted in a reduction in the protein expressions of cytochrome c, Bax, Apaf-1, caspase 9, caspase 3 (p17), caspase 8, caspase 6 and caspase 7 whereas it elevated the Bcl-2 in both the regions. Further, gene expressions of caspase 3 and caspase 9 were also found to be elevated after Al treatment, which however were reduced following Zn co-treatment. The electron-microscopic analysis of brain revealed that Al intoxication resulted in a number of degenerative signs at ultrastructural level, which were appreciably improved upon Zn supplementation. The present study suggests that Zn provides protection against Al induced neurotoxicity by triggering anti-apoptotic machinery.

Zinc modulates aluminium-induced oxidative stress and cellular injury in rat brain.

Dysregulation of metal homeostasis has been perceived as one of the key factors in the progression of neurodegeneration. Aluminium (Al) has been considered as a major risk factor, which is linked to several neurodegenerative diseases, especially Alzheimer's disease, whereas zinc (Zn) has been reported as a vital dietary element, which regulates a number of physiological processes in central nervous system. The present study was conducted to explore the protective potential of zinc, if any, in ameliorating neurotoxicity induced by aluminium. Male Sprague Dawley rats received either aluminium chloride (AlCl3) orally (100 mg kg(-1) b.wt. per day), zinc sulphate (ZnSO4) at a dose level of 227 mg L(-1) in drinking water or combined treatment of aluminium and zinc for 8 weeks. Aluminium treatment significantly elevated the levels of lipid peroxidation and reactive oxygen species as well as the activities of catalase, superoxide dismutase and glutathione reductase, which however were decreased following Zn co-treatment of Al-treated rats. In contrast, Al treatment decreased the activities of glutathione-S-transferase as well as the levels of reduced glutathione, oxidised glutathione and total glutathione, but co-administration of Zn to Al-treated animals increased these levels. Furthermore, Al treatment caused a significant increase in the levels of Fe and Mn as well as of Al but decreased the Zn and metallothionein levels. In the Zn-supplemented animals, the levels of Al, Fe, Mn were found to be significantly decreased, whereas the levels of metallothionein as well as Zn were increased. Moreover, histopathological alterations such as vacuolization and loss of Purkinje cells were also evident following Al treatment, which showed improvement upon Zn supplementation. Therefore, zinc has the potential to alleviate aluminium-induced neurodegeneration.

Moderate zinc supplementation during prolonged steroid therapy exacerbates bone loss in rats.

The present study was conducted to understand the influence of zinc on bone mineral metabolism in prednisolone-treated rats. Disturbance in bone mineral metabolism was induced in rats by subjecting them to prednisolone treatment for a period of 8 weeks. Female rats aged 6-8 weeks weighing 150 to 200 g were divided into four treatment groups, viz., normal control, prednisolone-treated (40 mg/kg body weight orally, thrice a week), zinc-treated (227 mg/L in drinking water, daily), and combined prednisolone + zinc-treated groups. Parameters such as changes in mineral levels in the bone and serum, bone mineral density (BMD), bone mineral content (BMC), and bone 99m-technetium-labeled methylene diphosphonate ((99m)Tc-MDP) uptake were studied in various treatment groups. Prednisolone treatment caused an appreciable decrease in calcium levels both in the bone and serum and also in bone dry weight, BMC, and BMD in rats. Prednisolone-treated rats when supplemented with zinc showed further reduction in calcium levels, bone dry weight, BMD, and BMC. The study therefore revealed that moderate intake of zinc as a nutritional supplement during steroid therapy could enhance calcium deficiency in the body and accelerate bone loss.

Influence of zinc on calcium-dependent signal transduction pathways during aluminium-induced neurodegeneration.

Metals perform important functions in the normal physiological system, and alterations in their levels may lead to a number of diseases. Aluminium (Al) has been implicated as a major risk factor, which is linked to several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. On the other hand, zinc (Zn) is considered as a neuromodulator and an essential dietary element that regulates a number of biological activities in our body. The aim of the present study was to investigate the effects of Zn supplementation, if any, in ameliorating the changes induced by Al on calcium signalling pathway. Male Sprague Dawley rats weighing 140-160 g were divided into four different groups viz.: normal control, aluminium treated (100 mg/kg b.wt./day via oral gavage), zinc treated (227 mg/l in drinking water) and combined aluminium and zinc treated. All the treatments were carried out for a total duration of 8 weeks. Al treatment decreased the Ca(2+) ATPase activity whereas increased the levels of 3', 5'-cyclic adenosine monophosphate, intracellular calcium and total calcium content in both the cerebrum and cerebellum, which, however, were modulated upon Zn supplementation. Al treatment exhibited a significant elevation in the protein expressions of phospholipase C, inositol triphosphate and protein kinase A but decreased the expression of protein kinase C, which, however, was reversed upon Zn co-treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of calcium deposits, which were improved upon zinc co-administration. The present study, therefore, suggests that zinc regulates the intracellular calcium signalling pathway during aluminium-induced neurodegeneration.

Protective role of zinc during aluminum-induced hepatotoxicity.

The study was carried out to assess the role of zinc (Zn) in mitigating the biochemical alterations induced by aluminum (Al) in rat liver. Rats were divided into four groups: normal control, Al treated (AlCl3, 100 mg/kg b.wt./day), Zn treated (ZnSO4, 227 mg/L drinking water), and combined Al + Zn treated. Al and zinc treatments were given for a total duration of 2 months. Al treatment caused a significant increase in the activity of alkaline phosphatase (ALP), but decreased aspartate aminotransferase (AST) and alanine aminotranferase (ALT) activities, which showed the reverse trend following Zn supplementation. Levels of lipid peroxidation (LPx) and activities of catalase and glutathione-S-transferase (GST) were significantly decreased following Al treatment, which, however, were increased significantly in Zn co-treated rats. Further Al exposure showed a significant increase in reduced glutathione (GSH) content as well as activities, of superoxide dismutase (SOD) and glutathione reductase (GR). However, Zn supplementation to Al-treated rats brought down the raised levels of reduced (GSH) and SOD to within normal limits, but caused no effect on GR activity. Furthermore, Al treatment also resulted in alterations in liver histoarchitecture with disruption of hepatic cords and increased vacuolization, which were close to normal following Zn supplementation. The present study reveals that Zn is effective in attenuating the liver damage inflicted by Al toxicity.

Influence of zinc on the biokinetics of (65)Zn in brain and whole body and its bio-distribution in aluminium-intoxicated rats.

The present study was designed to understand the influence of zinc (Zn) if any, on the biokinetics of (65)Zn in brain as well as whole body and its bio-distribution following aluminium (Al) treatment to rats. Male Sprague-Dawley rats weighing 140-160 g were divided into four different groups viz: normal control, aluminium treated (100 mg/kg b.wt./day via oral gavage), zinc treated (227 mg/L in drinking water) and combined aluminium and zinc treated. All the treatments were carried out for a total duration of 8 weeks. Al treatment showed a significant increase in fast component (Tb1) but revealed a significant decrease in slow component (Tb2) of biological half-life in brain as well as in whole body. However, Zn supplementation to Al-treated rats reversed the trend in both brain and whole body, which indicates a significant decrease in Tb1 component while the Tb2 component was significantly increased. Further, Al treatment showed an increased percent uptake value of (65)Zn in cerebrum, cerebellum, heart, liver and lungs whereas a decrease in uptake was found only in blood. On the other hand, there was a significant decline in (65)Zn activity in nuclear and mitochondrial fractions of brain of Al-treated rats. However, Zn treatment reversed the altered (65)Zn uptake values in different organs as well as in various subcellular fractions. The study demonstrates that Zn shall prove to be effective in regulating the biokinetics of (65)Zn in brain and whole body and its distribution at the tissue and subcellular levels in Al-treated rats.

Zinc, a neuroprotective agent against aluminum-induced oxidative DNA injury.

Aluminum (Al) has been considered as one of the most abundant elements and comprises nearly 8 % of the Earth's crust. Despite of its immense presence, studies regarding the molecular basis of its interaction with the physiological system are rather sparse. On the other hand, zinc (Zn), an essential micronutrient, has been regarded as the second most important metal for brain functioning. The objective of the present study was to investigate the protective potential of Zn, if any, during Al-induced detrimental effects on DNA, tritiated thymidine uptake as well as expression of stress marker genes and proteins in rat brain. Male Sprague-Dawley rats weighing 140-160 g were divided into four different groups viz.: normal control, Al treated (100 mg/kg b wt/day via oral gavage), Zn treated (227 mg/l in drinking water), and combined Al and Zn treated. All the treatments were carried out for a total duration of 8 weeks. Agarose gel electrophoresis revealed DNA laddering pattern and comets in the rat brain following Al treatment, which however, were attenuated upon Zn treatment. Further, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, number of apoptotic brain cells, and uptake of tritiated thymidine were increased after Al treatment but were decreased upon Zn supplementation. Western blot and mRNA expressions of p53 and nuclear factor κB (NF-κB) were also found to be significantly elevated after Al treatment, which however, were reversed following Zn treatment. Hence, Zn shall prove to be an effective agent in mitigating the detrimental effects caused by Al in the rat brain.

Modulation of Fourier transform infrared spectra and total sialic acid levels by selenium during 1,2 dimethylhydrazine-induced colon carcinogenesis in rats.

The present study investigated the modulatory potential of selenium supplementation, if any, on Fourier transform infrared (FTIR) spectra in brush border membranes (BBM) of colons and on serum total sialic acid as well as lipid bound sialic acid during 1,2 dimethyl hydrazine (DMH)-induced colorectal carcinogenesis in rats. The FTIR spectra of BBM from the colons of DMH-treated rats revealed a significant increase in the lipid contents but showed a significant decline in the protein contents. Further, decrease in the collagen as well as creatine contents was also noticed in the colons of DMH-treated rats. Supplementation with selenium appreciably restored protein as well as collagen contents and resulted in decreased lipids levels in the colons of DMH-treated rats. Interestingly, a significant increase in the levels of total sialic acid in serum of DMH-treated rats was observed which, however, got moderated significantly upon selenium supplementation. Moreover, no significant changes were observed in the levels of lipid bound sialic acid in all the treated groups as compared to controls. In conclusion, the present study suggested that supplementation of selenium act as a chemopreventive agent and delays considerably the process of colon carcinogenesis.

Zinc protection against aluminium induced altered lipid profile and membrane integrity.

The aim of the present study was to investigate the effects of Zinc (Zn) supplementation on lipid profile and fluidity of cerebrum and cerebellum membranes of rats treated with aluminium (Al). Sprague dawley male rats were divided into four different treatment groups viz: Control, aluminium treated, zinc treated and aluminium+zinc treated. Aluminium (AlCl3) was administered orally at a dose of 100mg/kgb.wt./day (dissolved in drinking water). Zinc as zinc sulphate was supplemented to rats at a dose of 227mg/l in drinking water. A significant decrease in the levels of total lipids, glycolipids, phospholipids, cholesterol and gangliosides contents were observed in both the cerebrum and cerebellum following Al exposure, which were found to be significantly increased following Zn supplementation. On the contrary, Al treatment caused a significant increase in the formation of conjugated dienes, which were observed to be reduced on Zn co-treatment. Further, Al treatment significantly elevated the fluorescence polarization, anisotropy and order parameter, which however were normalized upon Zn co-administration. Hence, the present study depicts the potential of Zn in moderating the changes caused by Al on membrane composition and fluidity in rat brain.

Chemopreventive effects of selenium on cancer marker indices and ultrastructural changes during 1,2 dimethylhydrazine-induced colon carcinogenesis in rats.

PURPOSE: The present study was conducted to elucidate the potential of selenium supplementation, if any, in affording chemoprevention by modulating the altered cancer markers and ultrastructural changes in dimethyl hydrazine (DMH)-induced colorectal carcinogenesis in rats. METHODS: The rats were segregated into four groups, viz., normal control, DMH treated, selenium treated, and DMH + selenium treated. Initiation and induction of colon carcinogenesis was achieved through weekly subcutaneous injections of DMH (30 mg/kg body weight) for both 10 and 20 weeks. Selenium was supplemented to rats at a dose level of 1 ppm in drinking water ad libitum for two different time durations of 10 and 20 weeks. RESULTS: The study observed a significant increase in the number of aberrant crypt foci (ACF) in colons of DMH-treated rats at both time intervals which were decreased significantly upon selenium supplementation. Also, a significant increase was seen in the enzyme activity of alkaline phosphatase (ALP), which, however, was moderated upon selenium administration to DMH-treated rats. Changes in the ultrastructural architecture of colonic cells were apparent following both the treatment schedules of DMH; however, the changes were prominent following 20 weeks of DMH treatment. The most obvious changes were seen in the form of altered nuclear shape and disruption of cellular integrity, which, upon selenium supplementation, were appreciably improved. CONCLUSION: In conclusion, the study shows the chemopreventive abilities of selenium against DMH-induced colorectal carcinogenesis in rats.

Selenium as a modulator of membrane stability parameters and surface changes during the initiation phase of 1,2-dimethylhydrazine induced colorectal carcinogenesis.

The present study evaluated the modulatory potential of selenium on colonic surface abnormalities and membrane fluidity changes following 1,2-dimethylhydrazine (DMH) induced colon carcinogenesis. Rats were segregated into four groups viz., normal control, DMH treated, selenium treated, and DMH + selenium treated. Initiation of molecular events leading to colon carcinogenesis was started following weekly subcutaneous injections of DMH (30 mg/Kg body weight) for 10 weeks. Selenium in the form of sodium selenite was supplemented to rats at a dose level of 1 PPM in drinking water, ad libitum for the entire duration of the study. Brush border membranes were isolated from the colon of rats and the viscosity as well as fluidity parameters were assessed using the membrane extrinsic fluorophore pyrene. DMH treatment resulted in a significant increase in lipid peroxidation. Reduced glutathione levels (GSH) and the activities of glutathione reductase (GR), glutathione transferase (GST), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were found to be significantly decreased following DMH treatment. On the other hand, supplementation with selenium to DMH treated rats resulted in a significant decrease in the levels of lipid peroxidation but caused a significant increase in the levels of GSH as well in the activities of GR, GST, SOD, CAT, and GPx. The results further, demonstrated a marked decrease in membrane microviscosity following DMH treatment. On the other hand, a significant increase was observed in the excimer/monomer ratio and fluidity parameter of DMH treated rats when compared to normal control rats. However, the alterations in membrane microviscosity and the fluidity parameters were significantly restored following selenium treatment. Further, histological as well as colon surface alterations were also observed following DMH treatment, which however were greatly prevented upon selenium co-administration. The study, therefore, concludes that selenium proves as a useful in modulating the colonic surface abnormalities and membrane stability following DMH induced colon carcinogenesis.

Premature mitochondrial senescence and related ultrastructural changes during lung carcinogenesis modulation by curcumin and resveratrol.

The present study attempted to explore the efficacy of curcumin and resveratrol in modulating premature mitochondria senescence and ultrastructural changes during lung carcinogenesis. The mice were segregated into 5 groups, which included normal control, benzo[a]pyrene (BP) treated, BP + curcumin (C) treated, BP + resveratrol (R) treated, and BP + C + R treated groups. Animals were given a single ip injection of benzo[a]pyrene in corn oil at a dose level of 100 mg/kg body weight. Treatments of curcumin and resveratrol were given orally in drinking water at a dose level of 60 mg/kg body weight and 5.7 µg/mL drinking water, respectively, 3 times a week for a total duration of 22 weeks. Ultrastructure of BP-treated mice revealed disruptions in cellular integrity along with nuclear deformation and premature mitochondrial senescence. Interestingly, supplementation of curcumin and resveratrol individually resulted in improvement of ultrahistoarchitecture of BP-treated mice but the improvement was much greater with combined supplementation of phytochemicals. Further, benzo[a]pyrene treatment revealed alterations in lung histoarchitecture, which, however, was improved appreciably following combined supplementation with curcumin and resveratrol. The present study concludes that combined supplementation with curcumin and resveratrol effectively modulates histoarchitecture as well as ultrahistoarchitecture during benzo[a]pyrene-induced lung carcinogenesis in mice. Cancer is a public health problem worldwide. Lung cancer is a major cause of mortality throughout the world and is responsible for the deaths of more than one million people annually. Phytochemicals have shown great potential in preventing the occurrence of cancer and other chronic diseases that result from oxidative stress induced by free radicals. Phytochemicals are nonnutritive products of plants and, being nontoxic, are presently being studied the world over for their chemopreventive actions in controlling various diseases, including cancer. In the present study, curcumin and resveratrol are the phytochemicals of interest. Curcumin, a polyphenol, has been reported to have anti-invasive properties. Further, curcumin has been shown to activate apoptotic machinery in patients with lung cancer. On the other hand, resveratrol (trans-3,4,5- thihydroxystibene) is a phytoalexin that is present naturally in grapes as well as in a variety of medicinal plants and has been shown to exhibit antioxidant activity with a potential to induce apoptosis.