In vitro and in vivo removal efficacy of insoluble Prussian blue in combination with calcium polystyrene sulfonate for thallium.

The similarities between thallium and potassium have suggested the use of calcium polystyrene sulfonate (CPS), an oral ion exchange resin, as a potential agent against thallium intoxication. Therefore, the study was an attempt to evaluate the efficacy of CPS and Prussian blue when given alone or in combination against thallium toxicity. The effect on binding capacity was investigated in terms of contact time, amount of CPS, influence of pH, simulated physiological solutions and interference of potassium ions. Also, rats were given single dose of thallium chloride (20 mg kg-1) and the treatment with PB and CPS was given for 28 days as CPS 30 g kg-1, orally, twice a day, PB 3 g kg-1, orally, twice a day and their combination. The effect of antidotal treatment was evaluated by calculating the thallium levels in various organs, blood, urine and feces. The results of the in vitro study indicated exceedingly quick binding in the combination of CPS and PB as compared to PB alone. Also, it was found that the binding capacity at pH 2.0 was considerably increased for PB with CPS (184.656 mg g-1) as compared to PB (37.771 mg g-1). Furthermore, statistically significant results were obtained in the in vivo study as after 7th day, thallium levels in blood of rats treated with combination were reduced by 64% as compared to control group and 52% as compared to alone PB treated group. Also, Tl retention in liver, kidney, stomach, colon and small intestine of combination treated rats was significantly reduced to 46%, 28%, 41%, 32% and 33% respectively, as compared to alone PB treated group. These findings demonstrate this as a good antidotal option against thallium intoxication.

Association Between Treatments and Short-Term Biochemical Improvements and Clinical Outcomes in Post-Severe Acute Respiratory Syndrome Coronavirus-2 Inflammatory Syndrome.

OBJECTIVES: To 1) analyze the short-term biochemical improvements and clinical outcomes following treatment of children with post-severe acute respiratory syndrome coronavirus-2 inflammatory syndrome (multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2) admitted to U.K. PICUs and 2) collate current treatment guidance from U.K. PICUs. DESIGN: Multicenter observational study. SETTING: Twenty-one U.K. PICUs. PATIENTS: Children (< 18 yr) admitted to U.K. PICUs between April 1, 2020, and May 10, 2020, fulfilling the U.K. case definition of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Routinely collected, deidentified data were analyzed. Propensity score and linear mixed effects models were used to analyze the effect of steroids, IV immunoglobulin, and biologic agents on changes in C-reactive protein, platelet counts, and lymphocyte counts over the course of PICU stay. Treatment recommendations from U.K. clinical guidelines were analyzed. Over the 6-week study period, 59 of 78 children (76%) received IV immunoglobulin, 57 of 78 (73%) steroids, and 18 of 78 (24%) a biologic agent. We found no evidence of a difference in response in clinical markers of inflammation between patients with multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 who were treated with IV immunoglobulin, steroids, or biologics, compared with those who were not. By the end of the study period, most patients had received immunomodulation. The 12 patients who did not receive any immunomodulators had similar decrease in inflammatory markers as those treated. Of the 14 guidelines analyzed, the use of IV immunoglobulin, steroids, and biologics was universally recommended. CONCLUSIONS: We were unable to identify any short-term benefit from any of the treatments, or treatment combinations, administered. Despite a lack of evidence, treatment guidelines for multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 have become very similar in advising step-wise treatments. Retaining clinical equipoise regarding treatment will allow clinicians to enroll children in robust clinical trials to determine the optimal treatment for this novel important condition.

Chemopreventive role of arabinogalactan against experimentally induced pulmonary carcinogenesis: a study in relation to its initiation phase.

The aim of the present study is to divulge the chemopreventive potential of arabinogalactan (AG) on benzo(a)pyrene [B(a)P] induced initiation of lung carcinogenesis. AG is one of the naturally occurring bioactive polysaccharides which is widely found in medicinal plants. Male Balb/c mice were divided into four experimental groups. Group I served as control. Group II animals were injected with B(a)P (50 mg/kg b. wt. i.p.). Group III animals were administered with AG (7.5 mg/kg b.wt.) orally. Group IV animals received B(a)P and AG as in group II and group III, respectively. B(a)P treatment in mice resulted in imbalance of carcinogen metabolizing enzymes and respiratory marker enzymes at 2nd, 6th and 10th week of the experimental protocol. Also, it leads to the increased protein synthesis as depicted by increased argyrophilic nucleolar organizer regions (AgNOR) positive cells and altered histopathological features. Studies on bronchoalveolar lavage fluid (balf) of B(a)P exposed animals revealed increase in surface tension when compared with control counterparts. Apart from target tissue (lung), B(a)P also led to the clastogenic damage in other tissues (spleen and bone marrow) as depicted by increase in percentage of micronucleus cells at different time intervals. Treatment with AG efficiently counteracted all the above anomalies and restored cellular homeostasis. These observations suggest that AG has the potential to modulate B(a)P induced changes in the pulmonary tissue as well as other tissues which could have implications in delaying the initiation of carcinogenesis, however, further investigations are required to explore its complete mechanism of action.

Acute Kidney Injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic: Experience From PICUs Across United Kingdom.

OBJECTIVES: To study the prevalence, evolution, and clinical factors associated with acute kidney injury in children admitted to PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. DESIGN: Multicenter observational study. SETTING: Fifteen PICUs across the United Kingdom. PATIENTS: Patients admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 between March 14, 2020, and May 20, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deidentified data collected as part of routine clinical care were analyzed. All children were diagnosed and staged for acute kidney injury based on the level of serum creatinine above the upper limit of reference interval values according to published guidance. Severe acute kidney injury was defined as stage 2/3 acute kidney injury. Uni- and multivariable analyses were performed to study the association between demographic data, clinical features, markers of inflammation and cardiac injury, and severe acute kidney injury. Over the study period, 116 patients with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 were admitted to 15 United Kingdom PICUs. Any-stage acute kidney injury occurred in 48 of 116 patients (41.4%) and severe acute kidney injury in 32 of 116 (27.6%) patients, which was mostly evident at admission (24/32, 75%). In univariable analysis, body mass index, hyperferritinemia, high C-reactive protein, Pediatric Index of Mortality 3 score, vasoactive medication, and invasive mechanical ventilation were associated with severe acute kidney injury. In multivariable logistic regression, hyperferritinemia was associated with severe acute kidney injury (compared with nonsevere acute kidney injury; adjusted odds ratio 1.04; 95% CI, 1.01-1.08; p = 0.04). Severe acute kidney injury was associated with longer PICU stay (median 5 days [interquartile range, 4-7 d] vs 3 days [interquartile range, 1.5-5 d]; p < 0.001) and increased duration of invasive mechanical ventilation (median 4 days [interquartile range, 2-6 d] vs 2 days [interquartile range, 1-3 d]; p = 0.04). CONCLUSIONS: Severe acute kidney injury occurred in just over a quarter of children admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. Hyperferritinemia was significantly associated with severe acute kidney injury. Severe acute kidney injury was associated with increased duration of stay and ventilation. Although short-term outcomes for acute kidney injury in pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 appear good, long-term outcomes are unknown.

Lycopene enriched tomato extract suppresses chemically induced skin tumorigenesis in mice.

The present study revealed the effects of Lycopene enriched tomato extract (LycT) on chemically induced skin cancer in mice. Skin tumors were induced by topical application of 7,12-Dimethylbenz(a)anthracene (DMBA) [500 nmol/100 ul of acetone, twice a week for two weeks] and 12-O-tetradecanoyl phorbol-13-acetate (TPA) [1.7 nmol/100 ul of acetone, twice a week for eighteen weeks] and LycT (5 mg/kg b.w.) was administered orally. Male Balb/c mice were divided into four groups (n = 15 per group): control, DMBA/TPA, LycT and LycT + DMBA/TPA. The chemopreventive response of LycT to skin tumorigenesis was evident by inhibition in tumor incidence, number, size, burden and volume in LycT + DMBA/TPA group when compared to DMBA/TPA group. This was associated with inhibition of cell proliferation in LycT + DMBA/TPA group as observed by the decrease in epidermal morphometric parameters and mRNA and protein expression of proliferating cell nuclear antigen when compared to DMBA/TPA group (p ≤ 0.05). LycT decreased (p ≤ 0.05) the mRNA and protein expression of angiogenic genes (vascular endothelial growth factor, angiopoietin-2, basic fibroblast growth factor) in LycT + DMBA/TPA group, suggesting its anti-angiogenic effects. The increase (p ≤ 0.05) in protein expression of connexin-32 and 43 in LycT + DMBA/TPA group suggests improved inter cellular communication when compared to DMBA/TPA group. Histochemical studies demonstrated that the components of extracellular matrix (fibrous proteins and mucopolysaccharides) were also modulated during skin carcinogenesis and its chemoprevention by LycT. The decrease in cell proliferation parameters and expression of angiogenesis associated genes, modulation of ECM components and increase in expression of connexins suggest that LycT improved multiple dysregulated processes during chemoprevention of skin cancer.

Ellagic acid ameliorates cisplatin toxicity in chemically induced colon carcinogenesis.

Cis-diamminedichloroplatinum(II) (cisplatin) (CP) is an important chemotherapeutic agent used in the treatment of several cancers. However, it has several side effects including nephrotoxicity gonadotoxicity, hepatotoxicity, and ototoxicity. In in vitro experiments, antioxidants or reactive oxygen species scavengers have a cytoprotective effect on cells exposed to cisplatin (CP). Ellagic acid (EA) is one such bioactive polyphenol that is abundant in some fruits, nuts, and seeds. Various authors have reported that EA has strong antioxidant and antitumor potential. The present study was, therefore, carried out to explore the protective potential of EA on CP-induced gonadotoxicity and nephrotoxicity in colon tumor-bearing mice. Animals were divided into five groups: Group I: normal control, Group II: DMH treated. After 20 weeks of DMH treatment, the animals were divided into four subgroups, viz., Group III: no treatment, Group IV: EA, Group V: CP, and Group VI: CP + EA. Administration of EA significantly ameliorated the toxicity caused by CP as indicated by improved kidney function tests and reproductive function tests. EA treatment to CP-abused mice also led to a marked reduction in the extent of peroxidative damage to tissue as was evident from the improvement in the histopathological changes in kidney and testis. Blood counts were also improved on administration of EA to CP-treated mice. This article provides the evidence that antioxidant efficacy of EA has beneficial effects on CP-induced nephrotoxicity and gonadotoxicity and contributes to understanding the role of oxidative stress, and suggests several points as part of the mechanism of CP toxicity.

Ellagic acid ameliorates cisplatin induced hepatotoxicity in colon carcinogenesis.

The clinical application of cisplatin (CP), one of the most extensively used antineoplastic drug, is restricted by its numerous side effects. CP's antitumor potential resides in the free generation of reactive oxygen species leading to oxidative stress. This stress is a source of the side effects associated with its use. Ellagic acid (EA), a polyphenol is known to possess multiple health benefits owing to its antioxidant properties. EA is largely metabolized by the colon microbiota of different mammals and therefore was a polyphenol of choice in the present study. The present study was thus carried out to explore the protective potential of EA on CP induced hepatotoxicity in colon tumor bearing mice. The administration of EA (10 mg/kg bwt po daily for 6 weeks) significantly ameliorated the toxicity caused by CP (5 mg/kg bwt ip once a week for 4 weeks). Activities of liver marker enzymes and lactate dehydrogenase were brought back to normal. EA cotreatment also led to a marked reduction in the extent of peroxidative damage to liver tissue as was evident from the improvement in the histopathological changes observed and FT-IR analysis. The present study, therefore, suggests that the administration of EA reduces the CP-induced hepatotoxicity, thereby emerging out as a potential candidate for chemopreventive action.

Preventive Role of Vitamin D in Silica-Induced Skin Fibrosis: A Study in Relation to Oxidative Stress and Pro-Inflammatory Cytokines.

The protective effects of vitamin D analogue calcipotriol in silica-induced skin fibrosis were studied in the present study. Male BALB / c mice were divided into four groups; Control, Vitamin D, Silica and Silica+Vitamin D. Silica was administered as a single intradermal injection (40 µg / µL, dissolved in normal saline; particle size 1 - 5 µm) in the hind limbs of animals in Silica & Silica+Vitamin D group. Vitamin D group animals received topical application of 100µL of vitamin D solution (10-7M in Ethanol) daily for 12 weeks. Silica+Vitamin D group animals received co-treatment of silica and vitamin D as described for other groups. After 12 weeks of treatment, dermal thickness and hydroxyproline content of treated sections were measured. The TNF-α and IL-6 levels were measured in serum of all treated animals. The silica-induced oxidative stress was measured in terms of lipid peroxidation in skin tissue. Antioxidant defence system was assessed in terms of levels of reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. A significant increase in the dermal thickness and hydroxyproline content was observed after silica treatment (931 ± 57.98 to 1804.61 ± 146.20 µm)(p < 0.05). Vitamin D co-treatment reduced dermal thickness and hydroxyproline content compared to Silica group (p < 0.05). Similarly a decrease in TNF-α and IL-6 levels were also observed after vitamin D treatment. A significant reduction in oxidative stress in terms of lipid peroxidation (4.92 ± 0.70 to 2.40 ± 0.31 nmol / mg protein). Therefore, present study suggested that vitamin D could be an effective agent against silica-induced skin fibrosis and oxidative stress.

Lycopene Enriched Tomato Extract Inhibits Hypoxia, Angiogenesis, and Metastatic Markers in early Stage N-Nitrosodiethylamine Induced Hepatocellular Carcinoma.

Targeting altered pathways during initial stage of hepatocellular carcinoma (HCC) development is viewed as an effective and promising strategy to control this disease. Present study investigated the potential effect of lycopene-enriched tomato extract (LycT) on hypoxia-induced factor (HIF)-1α, HOX, VEGF, CD31, matrix metalloproteinase (MMP)-2, MMP-9, and alpha fetoprotein (AFP)expression during initial stages of N-nitrosodiethylamine (NDEA) induced HCC. Female Balb/c mice (8-10 wk) were assigned to 4 groups: control, NDEA (200 mg NDEA i.p./kg body weight, cumulative), LycT (5 mg lycopene orally/kg body weight; 3 times a week), and LycT + NDEA. LycT treatment began 2 wk before NDEA administration and continued until the end of the 10 wk study. The onset of HCC by NDEA was associated with significant alteration in serum biochemical markers [alanine transaminases (ALT), aspartate transaminases (AST), and alkaline phosphatases (ALP), lactate dehydrogenase (LDH), urea, A/G ratio, and bilirubin] and in liver histopathology. LycT treatment significantly reduced the levels of these markers. LycT treatment to NDEA mice also led to significant reduction in protein levels of AFP, HIF-1α, VEGF, CD31, MMP-2, and MMP-9 in comparison with NDEA group alone. These parameters are important biomarkers of hypoxia, angiogenesis, and metastasis, which reflect the advanced disease stage. The study provides evidence that prophylactic dietary supplementation with LycT may counteract HCC progression and/or protect against disease onset.

Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation.

This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action.

Protective effect of Azadirachta indica a. Juss against doxorubicin-induced cardiac toxicity in tumour bearing mice.

Doxorubicin (DOX) treatment (12 microg/g body weight, once a week for 2 weeks) resulted in a significant decrease in the heart rate along with an increase in QRS, ST, and QT intervals. Histopathological studies showed cardiomyocyte degeneration, cytoplasmic vacuolation and macrophage infiltration in cardiac tissue. A marked increase in the rate of apoptosis was also observed. An increased oxidative stress was evidenced by significantly higher levels of lipid peroxidation (LPO) and depletion of reduced glutathione. A decrease in the activity of cellular antioxidant defence enzymes was also observed. The decrease in the heart rate and ECG alterations were prevented significantly by AAILE (100 microg/g body weight, po) co-treatment, started two weeks prior to DOX treatment and continued till the termination of the experiment. The cardioprotection was also evident from histopathology and decrease in the rate of apoptosis in cardiomyocytes. AAILE co-treatment also prevented DOX-induced increase in LPO and decrease in antioxidant defence enzymes. The results suggest that AAILE administration prevents DOX-induced cardiotoxicity.

Azadirachta indica mitigates DMBA-induced hepatotoxicity: a biochemical and radiometric study.

The hepatoprotective potential of aqueous Azadirachta indica leaf extract (AAILE) was assessed against DMBA-induced hepatotoxicity. DMBA (7,12-dimethylbenz[a] anthracene) treatment (40 mg/kg body weight, ip) to male Balb/c mice resulted in the derailment of liver function as revealed by extremely slow clearance of 99mTc-mebrofenin from liver, elevated levels of alkaline phosphatase (ALP) and alanine transaminase (ALT), compared to control group. In addition, elevated micronuclei score and high apoptotic index indicated hepatogenotoxicity in DMBA-treated mice. DMBA treatment also upregulated cytochrome P450 (CYP), cytochrome b5 (Cyt b5) and decreased glutathione-S-transferase activity in hepatic tissue, compared to control group. Enhanced lipid peroxidation (LPO) levels along with decreased reduced glutathione (GSH) level were also observed in DMBA group, compared to control group. AAILE co-treatment (200 mg/kg body weight, po, thrice a week) for 8 weeks followed by DMBA injection showed significant improvement in hepatic status, as revealed by normalization of 99mTc-mebrofenin clearance rate, decreased ALP and ALT levels, reduced genotoxicity in terms of micronuclei score and apoptotic index. Levels of LPO were significantly decreased along with increased hepatic GST and GSH levels in AAILE + DMBA group, compared to DMBA group. However, no significant change was observed in hepatic CYP and Cyt b5 levels, compared to DMBA group. The results indicated that AAILE effectively ameliorated DMBA-induced hepatotoxicity.

Comparative hepato-ameliorative effects of Bambusa nutans fresh and fermented shoot extracts on STZ induced diabetic LACA mice.

Bamboo shoots are nutritionally rich source of antioxidants and bioactive compounds with immense therapeutic potentials. The fresh shoot is acrid and needs to be processed to make it palatable. Fermentation is one the best processing methods for long term storage and make the shoot palatable and enhance taste. This study aims to assess the prophylactic hepatoprotective effects of fresh and fermented B. nutans shoot aqueous extract (200 mg/kg b.w.) in STZ induced diabetic LACA mice. Both extracts effectively improved body weight loss, hyperglycemia, and hepatomegaly. Fresh shoot reduced LDH activity and LPO level by 26.1% and 46.6%, while fermented shoot reduced them by 51.5% and 55.8%, respectively. The fermented shoot extract group demonstrated a noteworthy decrease in liver enzymes (SGPT, SGOT, ALP, and bilirubin levels) and an increase in albumin and A/G ratio, with more substantial improvements compared to the group treated with fresh extract. Additionally, the extracts enhanced antioxidant activities and showed histological improvements in hepatocytes and central vein structure. The findings indicate that both fresh and fermented B. nutans extracts are non-toxic and possess hepatoprotective potential in hyperglycaemic liver dysfunction, with fermented shoot extract exhibiting superior efficacy suggesting its potential as a therapeutic agent for hyperglycemic liver conditions.

Evaluating the effect of lycopene from Lycopersicum esculentum on apoptosis during NDEA induced hepatocarcinogenesis.

The present study was aimed to examine the influence of lycopene from tomatoes (LycT) on apoptosis in N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis. Female Balb/c mice were randomly divided into four groups i.e. Control, NDEA, LycT and LycT+NDEA. Hepatic tissue from NDEA treated mice exhibited enhanced expression of anti-apoptotic gene bcl-2 and decreased expression of pro-apoptotic genes caspase 3, 9 and p53 when compared to control group. LycT intervention to NDEA challenged mice exhibited enhanced expression of caspase 3, 9 and p53 and decreased expression of bcl-2 when compared with NDEA treated animals. Enhanced DNA damage was revealed in NDEA and LycT+NDEA groups as revealed by comet assay. However, TUNEL assay indicated enhanced apoptosis in LycT+NDEA group when compared to NDEA group. Hepatic tissue of NDEA treated mice showed persistently high lipid peroxidation levels and glutathione redox ratio during the process of hepatocarcinogenesis. The observed enhanced apoptosis in LycT+NDEA group may be attributed to its differential effects on apoptosis associated genes and its ability to act as a pro-oxidant. These findings provide a rational mechanistic insight into the growth-inhibitory effects of lycopene against hepatic cancer.

Changes in the electrical properties at an early stage of mouse liver carcinogenesis.

The present investigation reports the changes in the electrical properties of hepatic tissue in the frequency range of 100 Hz to 5 MHz at an early stage of liver carcinogenesis using the four-pin electrode method. The hepatocarcinogenesis model was developed by intraperitoneal injection of N-nitrosodiethylamine (NDEA) to male Balb/c mice. Histopathological assessment revealed high-grade dysplasia in the liver of NDEA-treated animals. The ultrastructural investigations indicated the presence of large and clumped cells with inconspicuous cell boundaries. The treatment resulted in significant changes in the dielectric properties of the tissues. A decrease in tissue conductivity along with an increase in relative permittivity was observed. The biophysical changes correlated well with histoarchitectural and morphological changes. The alterations in architectural arrangement and membrane structure of cells may be responsible for the observed changes in the dielectric properties.

Spectroscopic characterization of lycopene extract from Lycopersicum esculentum (Tomato) and its evaluation as a chemopreventive agent against experimental hepatocarcinogenesis in mice.

The present study was designed to characterize the lycopene extract (LycT) prepared from tomatoes (Lycopersicum esculentum) and then to evaluate its chemopreventive efficacy in N-diethylnitrosamine (NDEA)-induced experimental hepatocarcinogenesis in female Balb/c mice. The extraction of lycopene was carried out using hexane/acetone/ethanol as an extracting medium and then characterized by ultraviolet-visible, nuclear magnetic resonance and Fourier transform infrared spectroscopy. Chemopreventive efficacy of characterized LycT in vivo was evaluated in terms of hepatic tumour incidence, multiplicity, burden, hepatosomatic index and animal survival rate. Results indicated that average lycopene content of the tomato was 11.6-14 mg/kg tomato weight. Spectroscopic data confirmed the structural characteristics of lycopene in the extract. In the animal study, reduction in tumour incidence (42.05%), tumour burden (1.39) and tumour multiplicity (3.42) was observed upon LycT pretreatment to NDEA-treated animals. Histopathological analysis unravelled that the increased survival rate in LycT + NDEA-treated animals was due to the delay in the formation of aggressive tumour nodules. These observations indicate that lycopene seems to be an able candidate for chemoprevention in hepatocarcinogenesis resulting from NDEA insults.

Phytomodulatory potential of lycopene from Lycopersicum esculentum against doxorubicin induced nephrotoxicity.

An elevated level of serum urea and creatinine was observed in doxorubicin (DOX) treated animals indicating DOX-induced nephrotoxicity. Enhanced lipid peroxidation (LPO) in the renal tissue was accompanied by a significant decrease in the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) activities. Administration of lycopene (LycT) extracted from tomato to DOX treated mice showed a significant reduction in serum creatinine and urea levels which were associated with significantly low levels of LPO and significantly enhanced level of GSH and related antioxidant enzymes activity (GPx, GR and CAT) when compared to DOX group. Histopathological analysis revealed severe damage in the renal tissue of DOX treated animals. However, animals pretreated with LycT were observed to have reduced damage. Thus, from present results it may be inferred that lycopene may be beneficial in mitigating DOX induced nephrotoxicity in mice.

Effect of (+)-catechin hydrate on oxidative stress induced by high sucrose and high fat diet in male Wistar rats.

Increased lipid peroxidation and reduced glutathione levels in liver of rats fed high sucrose high fat (HSHF) diet were normalized by concomitant administration of (+)-catechin hydrate. Plasma non-enzymatic antioxidants viz. alpha-tocopherol, ascorbic acid and total thiols decrease were also significantly less in rats administered with (+)-catechin hydrate concomitantly with HSHF diet. Thus the present results indicate that (+)-catechin hydrate has antioxidant activity and is effective in reducing oxidative stress. The study is of clinical importance as oxidative stress is known to be the cause of many clinical manifestations viz. cancer, Parkinson's disease, atherosclerosis, heart failure, myocardial infarction and many other diseases.

Modulation of cigarette smoke induced alterations by aqueous Ocimum sanctum leaf extract in pulmonary tissue of rodents.

Smoking has been associated with an increased risk of asthma, lung cancer, cardiovascular diseases, chronic bronchitis, and a massive amount of oxidative stress. The present study was undertaken to determine the modulatory effects of Holi Basil/Tulsi, (Ocimum sanctum) leaf extract on cigarette smoke-induced pulmonary damage in mice. Cigarette smoke (CS) inhalation increased the levels of pulmonary lipid peroxidation, and reactive oxygen species and decreased the levels of glutathione. Histoarchitectural alterations and enhanced tissue lactate dehydrogenase (LDH) activity in pulmonary tissue was distinctly indicative of damage. Enhanced mucin production was also observed through mucicarmine and Alcian Blue-Periodic Acid Schiff (PAS) staining. Increased expression of MUC5AC was also observed. Alterations in the lung were also evident through FTIR studies. Administration of Ocimum sanctum leaf extract (80 mg/kg b.w) to CS exposed mice ameliorated these alterations to a greater extent. These findings are suggestive of the fact that Ocimum sanctum leaf extract effectively modulated CS-induced deleterious effects on pulmonary tissue.

Exploration of anticancer potential of Lantadenes from weed Lantana camara: Synthesis, in silico, in vitro and in vivo studies.

Naturally occurring pentacyclic triterpenoids and their semisynthetic analogues have engrossed increasing attention for their anticancer potential and exhibiting promising role in discovery of new anticancer agents. Present study include the semi synthetic modifications of Lantadenes from the weed Lantana carama and their structures delineation by FT-IR, 1H-NMR, 13C-NMR & mass spectroscopy. All the compounds were scrutinized for in vitro cytotoxicity, ligand receptor interaction and in vivo anticancer studies. Most of the novel analogues displayed potent antiproliferative activity against A375 & A431 cancer cell lines and found superior to parent Lantadenes. In particular, 3ß-(4-Methoxybenzoyloxy)-22ß-senecioyloxy-olean-12-en-28-oic acid was found to be most suitable compound, with IC50 value of 3.027 µM aganist A375 cell line having least docking score (-69.40 kcal/mol). Promising anticancer potential of the lead was further indicated by significant reduction in tumor volume and burden in two stage carcinoma model. These findings suggests that the Lantadene derivatives may hold promising potential for the intervention of skin cancers.