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.

A concept of radiation hormesis: stimulation of antioxidant machinery in rats by low dose ionizing radiation.

OBJECTIVE: The concept of radiation hormesis has been the matter of discussion with regard to beneficial effects to biological systems from low doses of ionizing radiations. However, its molecular basis is not well understood till now and the present study is a step forward to elucidate how low levels of ionizing radiation prove beneficial for functioning of biological systems. MATERIAL AND METHODS: Female Wistar rats weighing 100-120g were divided into four different groups. Each group consisted of eight animals. The animals in Group I served as normal controls for Group II animals which were subjected to whole body X-rays exposure of 20rads and were sacrificed 6 hours following exposure. Group III animals served as normal controls for group IV animals which were given whole body X-rays radiation of 20rads and were sacrificed 24 hours following exposure. RESULTS: The levels of reduced glutathione (GSH), total glutathione (TG) were increased in liver, kidney, brain and blood after 6hrs as well as 24hrs following X-rays exposure. On the contrary, no significant change in the oxidized glutathione (GSSG) content was observed following X-rays irradiation in any of the organs. Further, the low dose of X-rays resulted in a significant decrease in the lipid peroxidation (LPO) in liver, kidney and brain, whereas it caused an increase in LPO levels in blood. The enzyme activities of catalase (CAT) as well as glutathione-S-transferase (GST) were also increased in different organs after X-rays exposure. Furthermore, low dose irradiation with X-rays caused a significant increase in the counts of total leukocytes, lymphocytes and eosinophils, whereas it decreased the counts of neutrophils as well as monocytes. Hence, our results clearly indicate that low dose X-rays radiation exposure stimulates endogenous antioxidant defense machinery and also causes an increase in whole blood lymphocytes and eosinophils responsible for providing key defenses. CONCLUSION: Low doses of X-rays exposure may afford radiation hormesis by providing protection to organs from oxidative injury and support immune reaction.

68Ga-Glutathione radio-complex as a new diagnostic probe for targeting colon cancer in rats.

OBJECTIVE: Glutathione (GSH) plays an important role in a horde of cellular events that include cell proliferation and apoptosis.The present study describes the radio-synthesis and characterization of gallium-68 (68Ga)-labelled glutathione for its application in radionuclide imaging of cancer. SUBJECT AND METHODS: The radio-synthesis of radio-complex 68Ga-GSH was performed by the direct labeling method. The developed radio-complex was subjected to quality control tests. Colon tumors were developed in healthy male Sprague Dawley (S.D) rats by giving subcutaneous injections of dimethylhydrazine (DMH) in order to monitor the uptake of 68Ga-GSH radio-complex. RESULTS: Gallium-68-labelled glutathione was synthesized with a labeling efficiency of 73.5%±1%. Percentage plasma protein binding and log Po/w values for the radio-complex were found to be 20%-30% and -0.223±0.12, respectively. A significantly higher percentage specific uptake value of newly developed 68Ga-GSH complex was observed in colon tumor in comparison to soft tissue at 90 minutes post administration thereby exhibiting specificity for cancerous cells, which was also witnessed significantly increased overtime from the ratio of colon tumor uptake to normal colon uptake (P≤0.05). CONCLUSION: Therefore, 68Ga-labelled glutathione can further be exploited for radionuclide imaging and assessment of tumor drug resistance in patients.

Chemoprevention by Probiotics During 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats.

BACKGROUND: Probiotics are believed to have properties that lower the risk of colon cancer. However, the mechanisms by which they exert their beneficial effects are relatively unknown. AIM: To assess the impact of probiotics in preventing induction of colon carcinogenesis in rats. METHODS: The rats were divided into six groups viz., normal control, Lactobacillus plantarum (AdF10)-treated, Lactobacillus rhamnosus GG (LGG)-treated, 1,2-dimethylhydrazine (DMH)-treated, L. plantarum (AdF10) + DMH-treated and L. rhamnosus GG (LGG) + DMH-treated. Both the probiotics were supplemented daily at a dose of 2 × 1010 cells per day. DMH at a dose of 30 mg/kg body weight was administered subcutaneously twice a week for the first 4 weeks and then once every week for a duration of 16 weeks. Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase as protein expression of genes involved in apoptosis were assessed during DMH-induced colon carcinogenesis in rats. RESULTS: DMH treatment decreased the activity of GSH, GPx, GST, SOD and catalase. However, AdF10 and LGG supplementation to DMH-treated rats significantly increased the activity of these enzymes. Further, DMH treatment revealed alterations in the protein expressions of various genes involved in the p53-mediated apoptotic pathway such as p53, p21, Bcl-2, Bax, caspase-9 and caspase-3, which, however, were shifted towards normal control levels upon simultaneous supplementation with probiotics. CONCLUSION: The present study suggests that probiotics can provide protection against oxidative stress and apoptotic-related protein disregulation during experimentally induced colon carcinogenesis.

Physiological uptake and retention of radiolabeled resveratrol loaded gold nanoparticles (99mTc-Res-AuNP) in colon cancer tissue.

When tagged with a suitable radionuclide, the cancer targeting properties of trans-resveratrol could be utilized to locate cancerous sites in the body using radionuclide imaging technique. However, the polyphenol due to its rapid and extensive metabolism exhibits low bioavailability in vivo. The study was designed to enhance the cancer targeting efficacy of radiolabeled resveratrol using nano-based technology. Technetium-99m labeled resveratrol loaded gold nanoparticles (Res-AuNP) were synthesized, characterized and evaluated for their cancer targeting efficacy in HT29 colon cancer cells and in animal cancer model. Results of various investigations were compared to corresponding results obtained for 99mTc-AuNP and 99mTc-resveratrol. Cancer cell internalization observed for 99mTc-Res-AuNP was significantly higher than that of 99mTc-AuNP and 99mTc-resveratrol. Also, a gradual rise in target to nontarget uptake with time was observed following i.v. administration of 99mTc-Res-AuNP to colon tumor bearing rats, demonstrating better in vivo targeting of colon adenocarcinoma with 99mTc-Res-AuNP when compared to 99mTc-resveratrol.

Evaluation of 99m Tc-resveratrol as a colon cancer targeting probe.

The study aimed to evaluate cancer-targeting potential of a newly synthesised radiopharmaceutical, 99m Tc-resveratrol in vivo, using colon cancer model. Colon cancer was induced in 20 male Sprague-Dawley rats by subcutaneous administration of 1,2-dimethylhydrazine (DMH), dissolved in 1 mM EDTA-normal saline, at a dose of 30 mg/kg body weight twice a week for first 4 weeks and once a week for next 12 weeks. A control group containing normal rats was used for result comparison. Colon cancer in DMH-treated group was confirmed by gross analysis of the colon, by histopathological analysis and molecular marker study in tumour tissue. At the end of the treatment period, the animals from the two groups were used for bio-distribution evaluation of 99m Tc-resveratrol at different time intervals. High uptake of 99m Tc-resveratrol was recorded in rat liver, spleen and kidneys, and the ratio of colon tumour uptake to normal colon uptake in DMH-treated rats increased significantly (P ≤ 0.01) with time, to reach a maximum value at 2 h but decreased thereafter. High uptake at the tumour site as compared to normal colon tissue was observed; however, the uptake by cancer cells at the target site was limited by high reticulo-endothelial uptake and rapid metabolism.

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.

Low dose X-irradiation mitigates diazepam induced depression in rat brain.

Depression is considered as one of the most prevalent health ailments. Various anti-depressant drugs have been used to provide succour to this ailment, but with little success and rather have resulted in many side effects. On the other hand, low dose of ionizing radiations are reported to exhibit many beneficial effects on human body by stimulating various biological processes. The present study was conducted to investigate the beneficial effects of low doses of X-rays, if any, during diazepam induced depression in rats. Female Sprague Dawley rats were segregated into four different groups viz: Normal control, Diazepam treated, X-irradiated and Diazepam + X-irradiated. Depression model was created in rats by subjecting them to diazepam treatment at a dosage of 2 mg/kg b.wt./day for 3 weeks. The skulls of animals belonging to X-irradiated and Diazepam + X-irradiated rats were X-irradiated with a single fraction of 0.5 Gy, given twice a day for 3 days, thereby delivered dose of 3 Gy. Diazepam treated animals showed significant alterations in the neurobehavior and neuro-histoarchitecture, which were improved after X-irradiation. Further, diazepam exposure significantly decreased the levels of neurotransmitters and acetylcholinesterase activity, but increased the monoamine oxidase activity in brain. Interestingly, X-rays exposure to diazepam treated rats increased the levels of neurotransmitters, acetylcholinesterase activity and decreased the monoamine oxidase activity. Further, depressed rats also showed increased oxidative stress with altered antioxidant parameters, which were normalized on X-rays exposure. The present study, suggests that low dose of ionizing radiations, shall prove to be an effective intervention and a novel therapy in controlling depression and possibly other brain related disorders.

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.

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.

Current view of zinc as a hepatoprotective agent in conditions of chlorpyrifos induced toxicity.

Human population bears the brunt of deadly hepatotoxic, neurodegenerative, behavioural and various other developmental disorders due to pesticide toxicity through environmental or occupational exposures. The application of pesticides to control pests in land and water has posed potential health hazards to live stock and wildlife including fishes, mammals, birds and humans. Therefore, various scientific approaches are being considered to tackle the problem of pesticide poisoning especially in developing economies. The role of essential trace elements as the promising and efficient preventive prophylactic agents without any toxicity and side effects in attenuating the adverse effects caused by pesticides, have been reported by various scientists, the world over. In this perspective, zinc, a key constituent of more than 300 mammalian enzymes and many transcription factors has proved its protective potential in various models of animal toxicity. The hepato-protective potential of zinc has been proved during various toxic states including pesticide toxicity. However, zinc warrants further examination with regard to documentation of specific molecular pathways to establish the exact mechanisms for zinc-mediated protection during pesticide toxicity.

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.

Modulatory effects of curcumin in conjunction with piperine on benzo(a)pyrene-mediated DNA adducts and biotransformation enzymes.

The antigenotoxic effects of curcumin alone and with piperine on benzo(a)pyrene-diol (BaP) epoxide DNA adducts (BaPDE-DNA adducts), and carcinogen biotransformation enzymes was investigated in liver and lung of mice. Male Swiss albino mice received curcumin (100 mgkg(-1) body weight) and piperine (20 mgkg(-1) body weight) separately as well as in combination orally in corn oil for 7 days as pretreatments and thereafter 2 h, BaP (125 mgkg(-1) body weight) was administered orally in corn oil. A single dose of BaP to normal mice increased the activities of ethoxyresorufin o-deethylase (EROD), pentoxyresorufin o-depentylase (PROD) and levels of BaPDE-DNA adducts in both the tissues. Quinone reductase (QR) activity was also elevated in the BaP-treated group in both liver and lung when compared with normal control group. Pretreatment of curcumin and curcumin plus piperine before administration of BaP significantly decreased the activities of EROD, PROD, and the level of BaPDE-DNA adducts with consequent increase in QR activities. The study clearly indicates that curcumin, when given in combination with piperine, is more effective in modulating BaPDE-DNA adducts (liver and lung), and activity of EROD (liver).

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.

Regulatory role of zinc during aluminium-induced altered carbohydrate metabolism in rat brain.

Aluminium is considered an environmental neurotoxicant and causes many neurological disorders, whereas zinc is vital for many biological functions. The present study was carried out to investigate the role of Zn, if any, in mitigating the adverse effects inflicted by Al on carbohydrate metabolism in rat brain. Male Sprague-Dawley rats weighing 140-160 g were divided into four different groups: normal control, Al-treated (100 mg/kg b.w./day in drinking water via oral gavage), Zn-treated (227mg/liter in drinking water), and combined Al- and Zn-treated rats. All the treatments were continued for 2 months, and their effects on carbohydrate-metabolizing enzymes were studied. Additionally, expressions of the proteins glycogen synthase kinase-3 (GSK3) and protein phosphatase (PP1), which help in regulating carbohydrate energy metabolism, were also studied. Al treatment resulted in increased activities of the glucose-6-phosphatase (G6P), glucose-6-isomerase (G6I), and lactate dehydrogenase (LDH), whereas the activities of hexokinase and succinate dehydrogenase (SDH) and glycogen content were decreased. Moreover, no significant change was observed in the biochemical parameters upon Zn supplementation alone. However, Zn supplementation to Al-treated rats was able to reduce significantly the Al-induced increased activities of G6P, G6I, and LDH, but it elevated the levels of hexokinase, SDH, and glycogen. Furthermore, Al treatment increased the protein expression of GSK3 and decreased the PP1 expression, which were found to be reversed upon Zn administration. Hence, Zn is effective in regulating theAl-induced alterations in carbohydrate metabolism.

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.

Synergistic effects of piperine and curcumin in modulating benzo(a)pyrene induced redox imbalance in mice lungs.

The objective of the present study was to evaluate the effects of curcumin alone and with adjuvant piperine against benzo(a)pyrene (BaP) induced oxidative stress in lungs of male Swiss albino mice. Mice were pretreated either with curcumin (100 mg/kg body weight), or piperine (20 mg/kg body weight), and in combination of both for one week, followed by single dose of benzo(a)pyrene (125 mg/kg body weight) treatment. Treatment with benzo(a)pyrene resulted in increased levels of lipid peroxides (LPO), protein carbonyl content (PCC) and with consequent decrease in the levels of tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and reduced glutathione (GSH), which however, were increased significantly following curcumin treatment, but the increase was more pronounced when piperine was used as an adjuvant. BaP treatment alone did not alter significantly the GST activity. Pretreatment with curcumin increased the GST activity in BaP treated group, which was enhanced further upon synergistic treatment with piperine and curcumin. Therefore, combined administration of curcumin and piperine shall prove to be more effective in attenuating BaP induced toxicity.

Supplementation of zinc mitigates the altered uptake and turnover of 65Zn in liver and whole body of diabetic rats.

Diabetes is a life threatening disease and its onset is linked with both environmental and genetic factors. Zinc metabolism gets altered during diabetes and results in many complications. The present study was designed to elucidate the effects of zinc supplementation on the biokinetics of (65)Zn in whole body, liver and its biodistribution in diabetic rats. The animals were divided into four groups viz; normal control; diabetic (single intraperitoneal injection of alloxan 150 mg/kg body weight); zinc treated (227 mg/l in drinking water); and diabetic + zinc treated. To carry out biokinetics study, each rat was injected intraperitoneally with 0.74 MBq radioactivity of (65)Zn following 4 weeks of different treatments and the radioactivity was determined by using a suitably shielded scintillation counter. Alloxan induced diabetic rats showed a significant decrease in both the fast (Tb(1)) and slow (Tb(2)) components of biological half-life of (65)Zn which, however, were normalized in whole body (P > 0.05) following zinc supplementation. In case of liver, Tb(2) component was brought back to the normal but Tb(1) component was not increased significantly. The present study indicates that the paucity of zinc in the tissues of the diabetic animals was due to decreased retention of tissue zinc as evidenced by increased serum Zn, hyperzincuria and increased rate of uptake of (65)Zn by the liver. Zinc supplementation caused a significant improvement in the retention of zinc in the tissues and is therefore likely to be of benefit in the treatment of diabetes.