Protective Effects of Arbutus unedo L. Honey in the Alleviation of Irinotecan-Induced Cytogenetic Damage in Human Lymphocytes-An In Vitro Study.

Strawberry tree (Arbutus unedo L.) honey (STH) has been used since ancient times as a folk medicine remedy, especially in certain Mediterranean countries. This honey, rich in phenolic content, is well recognized for its antioxidant, anti-inflammatory, and antimicrobial activities, and is used for the treatment of skin lesions as well as gastrointestinal and respiratory disorders. This study investigated whether STH alleviates genome damage in human peripheral blood lymphocytes produced by the cytotoxic drug irinotecan. The phenolic profile of STH was previously estimated by ultra-high-performance liquid chromatography coupled to a linear ion trap-Orbitrap hybrid mass spectrometer. The effects of STH were evaluated at three concentrations (1×, 5×, and 10×), based on the daily consumption of the honey by an adult person. After 2 h of in vitro exposure, standard lymphocyte cultures for the analysis of chromosome aberrations and the cytokinesis-block micronucleus cytome assay were established. Our results demonstrate that STH offered remarkable geno- and cytoprotection when administered with irinotecan. These findings are relevant for drawing preliminary conclusions regarding the in vitro safety of the tested honey. However, further studies are needed with the application of more complex experimental models.

Genetic Manipulation and Bioreactor Culture of Plants as a Tool for Industry and Its Applications.

In recent years, there has been a considerable increase in interest in the use of transgenic plants as sources of valuable secondary metabolites or recombinant proteins. This has been facilitated by the advent of genetic engineering technology with the possibility for direct modification of the expression of genes related to the biosynthesis of biologically active compounds. A wide range of research projects have yielded a number of efficient plant systems that produce specific secondary metabolites or recombinant proteins. Furthermore, the use of bioreactors allows production to be increased to industrial scales, which can quickly and cheaply deliver large amounts of material in a short time. The resulting plant production systems can function as small factories, and many of them that are targeted at a specific operation have been patented. This review paper summarizes the key research in the last ten years regarding the use of transgenic plants as small, green biofactories for the bioreactor-based production of secondary metabolites and recombinant proteins; it simultaneously examines the production of metabolites and recombinant proteins on an industrial scale and presents the current state of available patents in the field.

Liver function and DNA integrity in hepatocytes of rats evaluated after treatments with strawberry tree (Arbutus unedo L.) water leaf extract and arbutin.

Due to their beneficial health effects, strawberry tree (Arbutus unedo L.) leaves have for decades been used as herbal remedy in countries of the Mediterranean region. This pilot study is the first to investigate the liver function and DNA integrity in rat hepatocytes evaluated after 14 and 28 day treatments with strawberry tree water leaf extract and arbutin, administered per os to Lewis rats of both genders at a daily dose 200 mg/kg b.w. We focused on two types of biomarkers: enzyme serum markers of liver function (AST, ALT, and LDH), and primary DNA damage in the liver cells, which was estimated using the alkaline comet assay. At the tested dose, strawberry tree water leaf extract showed acceptable biocompatibility with liver tissue both in male and female rats, especially after shorter exposure. Our results also suggest that oral administration of single arbutin to rats was not associated with significant impairments either in the liver function or DNA integrity in hepatocytes. Considering that prolonged exposure to the tested compounds revealed minor changes in the studied biomarkers, future in vivo studies have to further clarify the biological and physiological relevance of these findings.

DNA Damaging Effects, Oxidative Stress Responses and Cholinesterase Activity in Blood and Brain of Wistar Rats Exposed to Δ9-Tetrahydrocannabinol.

Currently we are faced with an ever-growing use of Δ9-tetrahydrocannabinol (THC) preparations, often used as supportive therapies for various malignancies and neurological disorders. As some of illegally distributed forms of such preparations, like cannabis oils and butane hash oil, might contain over 80% of THC, their consumers can become intoxicated or experience various detrimental effects. This fact motivated us for the assessments of THC toxicity in vivo on a Wistar rat model, at a daily oral dose of 7 mg/kg which is comparable to those found in illicit preparations. The main objective of the present study was to establish the magnitude and dynamics of DNA breakage associated with THC exposure in white blood and brain cells of treated rats using the alkaline comet assay. The extent of oxidative stress after acute 24 h exposure to THC was also determined as well as changes in activities of plasma and brain cholinesterases (ChE) in THC-treated and control rats. The DNA of brain cells was more prone to breakage after THC treatment compared to DNA in white blood cells. Even though DNA damage quantified by the alkaline comet assay is subject to repair, its elevated level detected in the brain cells of THC-treated rats was reason for concern. Since neurons do not proliferate, increased levels of DNA damage present threats to these cells in terms of both viability and genome stability, while inefficient DNA repair might lead to their progressive loss. The present study contributes to existing knowledge with evidence that acute exposure to a high THC dose led to low-level DNA damage in white blood cells and brain cells of rats and induced oxidative stress in brain, but did not disturb ChE activities.

Irinotecan and Δ8-Tetrahydrocannabinol Interactions in Rat Liver: A Preliminary Evaluation Using Biochemical and Genotoxicity Markers.

There is growing interest regarding the use of herbal preparations based on Cannabis sativa for medicinal purposes, despite the poorly understood interactions of their main constituent Δ8-tetrahydrocannabinol (THC) with conventional drugs, especially cytostatics. The objective of this pilot study was to prove whether the concomitant intake of THC impaired liver function in male Wistar rats treated with the anticancer drug irinotecan (IRI), and evaluate the toxic effects associated with this exposure. IRI was administered once intraperitoneally (at 100 mg/kg of the body weight (b.w.)), while THC was administered per os repeatedly for 1, 3, and 7 days (at 7 mg/kg b.w.). Functional liver impairments were studied using biochemical markers of liver function (aspartate aminotransferase-AST, alanine aminotransferase-ALP, alkaline phosphatase-AP, and bilirubin) in rats given a combined treatment, single IRI, single THC, and control groups. Using common oxidative stress biomarkers, along with measurement of primary DNA damage in hepatocytes, the degree of impairments caused at the cellular level was also evaluated. THC caused a time-dependent enhancement of acute toxicity in IRI-treated rats, which was confirmed by body and liver weight reduction. Although single THC affected ALP and AP levels more than single IRI, the levels of liver function markers measured after the administration of a combined treatment mostly did not significantly differ from control. Combined exposure led to increased oxidative stress responses in 3- and 7-day treatments, compared to single IRI. Single IRI caused the highest DNA damage at all timepoints. Continuous 7-day oral exposure to single THC caused an increased mean value of comet tail length compared to its shorter treatments. Concomitant intake of THC slightly affected the levels of IRI genotoxicity at all timepoints, but not in a consistent manner. Further studies are needed to prove our preliminary observations, clarify the underlying mechanisms behind IRI and THC interactions, and unambiguously confirm or reject the assumptions made herein.

Assessment of multiple anthropogenic contaminants and their potential genotoxicity in the aquatic environment of Plitvice Lakes National Park, Croatia.

In this study, the influence of anthropogenic pollution on the aquatic environment of Plitvice Lakes National Park (PLNP) was investigated during 2011-2012 using a combination of chemical and cytogenetic analyses. Four groups of major contaminants [(volatile organic compounds: benzene, toluene, ethylbenzene, and xylenes (BTEX); persistent organochlorine pollutants: organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs); major and trace elements; anthropogenic radionuclides (90Sr, 134Cs, and 137Cs)] were determined in three aquatic compartments (water, sediment, fish). Mass fractions of inorganic constituents in different compartments reflected the geological background of the area, indicating their origin from predominantly natural sources. Levels of volatile and persistent organic compounds in water and fish, respectively, were very low, at levels typical for remote pristine areas. Analysis of anthropogenic radionuclides in water and sediment revealed elevated activity concentrations of 137Cs in water, and measurable 134Cs in the upper sediment layers from April 2011, possibly as a consequence of the Fukushima nuclear accident in March 2011. The potential genotoxicity of river and lake water and lake sediment was assessed under laboratory conditions using the alkaline comet assay on human peripheral blood lymphocytes, and measured levels of primary DNA damage were within acceptable boundaries. The results showed that despite the protected status of the park, anthropogenic impact exists in both its terrestrial and aquatic components. Although contaminant levels were low, further monitoring is recommended to make sure that they will not rise and cause potentially hazardous anthropogenic impacts.

Placental cadmium as an additional noninvasive bioindicator of active maternal tobacco smoking.

Tobacco smoke (TS) is a mixture of chemicals that is known to exert carcinogenic and endocrine-disrupting effects, as well as adverse effects on various systems. In TS nicotine is the major alkaloid and cadmium (Cd) the most abundant metal ion. The aim of this investigation was to assess exposure to Cd attributed to TS in healthy postpartum subjects (mean age 28 years) after term vaginal delivery in a clinical hospital by determining metal levels in maternal blood, placenta, and cord blood in relation to nicotine in maternal hair (12-cm-long samples). Two study groups were compared based upon self-reporting data: smokers (n = 32; continual cigarette smoking 3 months before and 9 months during pregnancy) and nonsmokers (n = 54; including passive smokers whose parameters did not differ from unexposed nonsmokers). In smokers compared to nonsmokers maternal hair nicotine concentrations increased approximately sevenfold, while Cd levels rose fourfold in maternal blood and up to twofold in placenta. Significant positive correlations were noted between maternal hair nicotine and placental Cd, maternal hair nicotine and maternal blood Cd, and placental Cd and maternal blood Cd. Levels of cord blood Cd were low in both study groups (<0.1 ng/ml). Data indicate that Cd in placenta may serve as a noninvasive bioindicator in addition to commonly used noninvasive hair nicotine in maternal TS assessment, especially in cases where unavailable or inappropriate (short or chemically treated) hair samples occur.

Elemental and Radiological Characterisation of Arbutus unedo L. Leaves and Tea: Impact of Preparation Method on Nutritional Risk/Benefit.

The aim of this study was to characterise the elemental and radiological composition of strawberry tree (Arbutus unedo L.) leaves and tea preparations and compare it with commercial Uvin H herbal mixture, widely used in treatment of urinary tract infections. The concentration of 17 elements and the activity concentration of selected radionuclides were measured in strawberry tree leaves/Uvin H herbal mixture, as well as in herbal tea prepared by infusion or decoction of leaves for 5 or 10 min. In both leaves and tea preparations, Ca, K, Mg, and Na were the most abundant elements, while the lowest levels were measured for As, Co, Mo, and Se. Only 137Cs and 40K were detected in analysed leaves/herbal mixture, while the activity of radionuclides in tea preparations was below the detection limit. The maximum possible health benefits can be obtained by a 10-min decoction of leaves, which resulted in the highest total phenolic content and antioxidant activity and levels of K, Ca, Mg, Na, Fe, Mn, and Se in comparison to the other preparation methods evaluated in this study. The calculated intake of potentially toxic elements and radionuclides does not represent a health risk to consumers.

Development of a solid phase microextraction method for the determination of nicotine in dried mushrooms.

Official control of EU market foodstuffs repeatedly reports high nicotine levels in dried wild mushrooms without any clear scientific consensus about their origin. The advised constant monitoring calls for improvements to existing methods. For this purpose, our aim was to develop a headspace solid phase microextraction (HS-SPME) method coupled to gas chromatography with mass spectrometric detection (GC-MS) that would eliminate the need for extensive sample pre-treatment. The type of fiber coating, amount of sample, extraction temperature and time, desorption time and salt addition were investigated and optimized as parameters affecting the SPME procedure. The optimized conditions were used to validate a quantitative method for nicotine analysis by matrix-matched calibration and isotopically labelled internal standard correction. The method provided good linearity (r2 = 0.9994) over the tested concentration range (0.025-1 mg kg-1), low detection limit (0.005 mg kg-1) and low quantification limit (0.017 mg kg-1) for nicotine, being below the EU foodstuff regulations. For both of the tested concentration levels (0.050 and 0.200 mg kg-1), precision expressed as relative standard deviation was below 10% (4.5% and 8.5%, respectively), while accuracy was 98.2% and 100.3%. The optimized method was then used to determine nicotine levels in 18 samples of dried Boletus mushrooms from southeastern European countries entering the EU market. We demonstrated our HS-SPME procedure to be fast, simple, sensitive, solvent-free, cost-effective and thus suitable for controlling consumer safety regarding nicotine level in dried mushrooms.

Development of a Pressurized Green Liquid Extraction Procedure to Recover Antioxidant Bioactive Compounds from Strawberry Tree Fruit (Arbutus unedo L.).

Strawberry tree fruits (Arbutus unedo L.) are a natural source of valuable biologically active compounds. Therefore, the aim of this work was to develop a green extraction approach using pressurized liquid extraction (PLE) to provide the highest yield of bioactive compounds. Different extraction solvents (distilled water, 50% and 96% ethanol) and different PLE parameters were investigated: temperature (40, 80, and 120 °C), static extraction time (5 and 10 min), and number of cycles (1 and 2). Total phenolic contents (TPC), hydroxycinnamic acids (HCA), flavonols (FL), total flavonoids (TF), condensed tannins (CT), and antioxidant capacity (DPPH and FRAP) were determined in PLE extracts. Solvent type, temperature, static extraction time, and number of cycles had a statistically significant effect on all bioactive compounds and antioxidant capacity (p ≤ 0.05). All bioactive compounds were positively correlated with temperature, except for TPC and DPPH. For all polyphenols studied, the optimal PLE parameters were a temperature of 120 °C, a static extraction time of 10 min and 2 cycles. The best solvent for most bioactive compounds was 96% ethanol, except for TPC, for which 50% ethanol was better. This study suggests that PLE is a promising tool to intensify the extraction of bioactive compounds from strawberry tree fruits.

Effects of Maternal Cigarette Smoking on Trace Element Levels and Steroidogenesis in the Maternal-Placental-Fetal Unit.

This study evaluates the interaction of toxic elements cadmium (Cd) and lead (Pb) due to exposure from cigarette smoking, essential elements, and steroidogenesis in the maternal-placental-fetal unit. In a cohort of 155 healthy, postpartum women with vaginal term deliveries in clinical hospitals in Zagreb, Croatia, samples of maternal blood/serum and urine, placental tissue, and umbilical cord blood/serum were collected at childbirth. The biomarkers determined were concentrations of Cd, Pb, iron (Fe), zinc (Zn), copper (Cu), and selenium (Se), and steroid hormones progesterone and estradiol in maternal and umbilical cord blood and the placenta. Three study groups were designated based on self-reported data on cigarette smoking habits and confirmed by urine cotinine levels: never smokers (n = 71), former smokers (n = 48), and active smokers (n = 36). Metal(loid)s, steroid hormones, urine cotinine, and creatinine levels were analyzed by ICP-MS, ELISA, GC-MS, and spectrophotometry. Cigarette smoking during pregnancy was associated with increased Cd levels in maternal, placental, and fetal compartments, Pb in the placenta, and with decreased Fe in the placenta. In active smokers, decreased progesterone and estradiol concentrations in cord blood serum were found, while sex steroid hormones did not change in either maternal serum or placenta. This study provides further evidence regarding toxic and essential metal(loid) interactions during prenatal life, and new data on sex steroid disruption in cord serum related to cigarette smoking. The results indicate that umbilical cord sex steroid levels may be a putative early marker of developmental origins of the future burden of disease related to harmful prenatal exposure to cigarette smoke.

Cytotoxic activity of strawberry tree (Arbutus unedo L.) honey, its extract, and homogentisic acid on CAL 27, HepG2, and Caco-2 cell lines.

Strawberry tree (Arbutus unedo L.) honey (STH), also known as "bitter honey", is a traditional medicine widely used in the Mediterranean area. Regardless of geographical origin, it usually has a very high content of phenolic compounds and strong antioxidant capacity. Yet, little is still known about the effects of STH, its phenolic extract (STHE), and its main bioactive compound - homogentisic acid (HGA) - at the cell level. The aim of this study was to estimate total phenolic content, DPPH radical scavenging activity, and ferric reducing antioxidant power of STH made in Croatia and investigate cytotoxic and pro-oxidative effects of STH, STHE and HGA on three human cell lines: tongue squamous cell carcinoma (CAL 27), hepatocellular carcinoma (HepG2), and epithelial colorectal adenocarcinoma cells (Caco-2) cells. These substances were tested at four concentrations (0.5-5× average human daily intake of STH) and over 30 min and 1 and 2 h. Croatian STH had a total phenolic content of 1.67 g gallic acid equivalents (GAE) per kg of honey, DPPH radical scavenging activity of 2.96 mmol Trolox equivalents (TE) per kg of honey, and ferric reducing antioxidant power (FRAP) of 13.5 mmol Fe2+ per kg of honey. Our results show no clear and consistent time- or concentration-dependent cytotoxicity in any of the cell lines. ROS levels in all the three cell types at almost all exposure times were not significantly higher than control. The most important observation is that the tested substances have low cytotoxicity and high biocompatibility, regardless of concentration, which is a good starting point for further research of their biological effects in other models.

Combined Inhibitory Effect of Fir (Abies alba Mill.) Honeydew Honey and Probiotic Bacteria Lactiplantibacillus plantarum on the Growth of Salmonella enterica Serotype Typhimurium.

Honey is a natural food consisting mainly of sugars, enzymes, amino acids, organic acids, vitamins, minerals and aromatic substances. In addition to specific organoleptic properties, honey also has other components that contribute to its nutritional and health value. Proteins, vitamins, minerals, organic acids and phenolic compounds, the most variable components of honey, are predominantly responsible for its strong bioactive effect. Honeydew honey is a less known type of honey with outstanding antimicrobial and antioxidant properties that also demonstrates prebiotic effects and can promote the growth of probiotic bacteria. Foodborne illnesses can be prevented by using probiotic strains in combination with prebiotics. The aim of this study was for the first time to determine potential synergistic antimicrobial effect of fir (Abies alba Mill.) honeydew honey (HS) and probiotic bacteria Lactiplantibacillus plantarum on Salmonella enterica serotype Typhimurium, a primary cause of foodborne illnesses. The effect of three different samples of fir honeydew honey on the growth of L. plantarum in de Man, Rogosa and Sharpe (MRS) medium and the potential synergistic effect of HSs and L. plantarum on the growth of S. Typhimurium in the Brain Heart Infusion (BHI) medium were examined. The results indicate that concentrations of 1 and 5% of all three HS samples stimulate the growth and metabolic activity of L. plantarum, while a concentration of 10% inhibits the growth of L. plantarum. The concentration of 5% of all three HS and L. plantarum combined inhibits the growth of S. Typhimurium in BHI broth. Fir honeydew honey showed potential prebiotic properties and antimicrobial activity, both of which can synergistically enhance the probiotic efficacy of L. plantarum against S. Typhimurium To conclude, the combination of fir honeydew honey and L. plantarum represents a successful combination against S. Typhimurium and additional experiments are necessary regarding the mechanisms of their combined effect.

Optimisation of a solid-phase microextraction method for the analysis of nicotine in hair.

A headspace solid-phase microextraction method (HS-SPME) followed by gas chromatography with mass spectrometric detection (GC/MS) has been developed for the determination of low concentrations of nicotine in hair. Parameters affecting the SPME procedure including type of fiber coating, extraction mode, extraction temperature and time, desorption time, stirring, and salt addition have been evaluated and optimised. The method provided good linearity (r(2)≥0.9980) over the concentration range tested (0.2-20 ng/mg) and low detection limit (0.02 ng/mg). Precision expressed as relative standard deviation was <10%. The average accuracy was 95%. The proposed method was used to determine hair nicotine levels in 100 children in order to assess exposure to environmental tobacco smoke (ETS). The described HS-SPME procedure is fast, simple, sensitive, and solvent-free and is therefore suitable for studies involving ETS exposure assessment.

Homogentisic acid, a main phenolic constituent of strawberry tree honey, protects human peripheral blood lymphocytes against irinotecan-induced cytogenetic damage in vitro.

Homogentisic acid (HGA) is the most abundant phenolic compound in strawberry tree (Arbutus unedo L.) honey and an intermediate in the metabolism of phenylalanine and tyrosine. Since HGA exerts its dual nature (pro-oxidant and antioxidant), which depends on the concentration and cell type, the aim of study was to determine whether HGA possess cytoprotective effects and could counteract the cyto- and genotoxic effects of the antineoplastic drug irinotecan (IRI). Tested concentrations corresponded to HGA content in average daily dose of strawberry tree honey as well as five- and ten-fold higher concentrations. Cyto- and genoprotective effects were tested on human peripheral blood lymphocytes using chromosomal aberrations assay and cytokinesis-block micronucleus cytome assay. HGA, even at concentrations 10-fold higher than the one present in the daily amount of consumed strawberry tree honey, posed a non-significant cytotoxic threat to lymphocytes, had a negligible potential for causing cytogenetic damage in treated cells, and did not significantly impair their proliferation. Results of the chromosomal aberration assay and CBMN Cyt assay also showed that HGA efficiently counteracted the detrimental cytogenetic effects of IRI in vitro. The finding on cyto- and genoprotective effects of HGA merits further research in order to better explain the safety profile of this compound and to assess its potency for the development of novel nutraceutical products.

Unauthorized Food Manipulation as a Criminal Offense: Food Authenticity, Legal Frameworks, Analytical Tools and Cases.

Food fraud is a criminal intent motivated by economic gain to adulterate or misrepresent food ingredients and packaging. The development of a reliable food supply system is at great risk under globalization, but Food Business Operators (FBOs) have a legal obligation to implement and maintain food traceability and quality at all stages of food production, processing, and distribution. Incidents of food fraud have a strong negative impact on consumer confidence in the food industry. Therefore, local and international regulatory mechanisms are established to prevent or mitigate food fraud. This review brings new perspectives linking EU and US legislation, as well as new definitions and descriptions of the criminal aspect of food fraud incidents. It also describes certain new insights into the application of state-of-the-art methods and techniques that provide valuable tools for geographic, botanical, or other chemical markers of food authenticity. The review also provides an overview of the most common cases of food fraud worldwide from 2010 to 2020. Further research is needed to support the development of predictive models for innovative approaches to adulteration, especially when some valuable nutrients are replaced by toxic ingredients. A possible solution to minimize food fraud incidents is to increase the level of risk-based inspections, establish more productive monitoring and implementation of food protection systems in the supply chain, and implement better ingredient control and certification. National and international (e.g., regional) police offices for food fraud should be introduced, possessing knowledge and skills in food, food safety, food processing, and food products, as initial positive results have emerged in some countries.

Comparative Study on the Phenolic Fingerprint and Antioxidant Activity of Strawberry Tree (Arbutus unedo L.) Leaves and Fruits.

The strawberry tree (Arbutus unedo L., Ericaceae family) is an evergreen Mediterranean shrub whose leaves and fruits are used in traditional medicine due to their antioxidant, antimicrobial, antidiabetic, diuretic, and antiproliferative properties. The health benefits are mainly attributed to the presence of phenolic compounds. The aim of this study was to compare the phenolic profiles, total phenolic content (TPC), and radical scavenging activity (RSA) of A. unedo leaves and fruits collected at two locations in Croatia. Phenolic profiles were identified using an ultra-high-performance liquid chromatograph (UHPLC) coupled with a hybrid mass spectrometer (LTQ Orbitrap MS). TPC was determined by Folin-Ciocalteu's assay, while RSA was investigated using DPPH reagent. A total of 64 phenolics (60 and 42 compounds in leaves and fruits, respectively) were identified. Hyperoside and flavan-3-ols were predominant compounds in leaves, while gallocatechin and catechin were the major compounds found in fruits. To the authors' knowledge, 16 and 5 phenolics in leaves and fruits, respectively, were reported for the first time. Principal component analysis (PCA) showed that UHPLC-LTQ Orbitrap MS could be used to identify which phenolics were able to discriminate samples regarding plant tissue and geographical origin. TPC in leaves and fruits were in the ranges of 67.07-104.74 and 16.78-25.86 mg gallic acid equivalents (GAE)/g dried weight (dw), respectively. RSA for leaves and fruits were in the ranges of 408.92-430.98 and 74.30-104.04 µmol Trolox equivalents (TE)/g dw, respectively. The number of identified phenolics was lower in fruits compared to leaves. Such a large number of bioactive phenolics identified and the strong antioxidant activity pointed to A. unedo as a promising health-promoting plant and natural food preservative.

The effects of strawberry tree (Arbutus unedo L.) water leaf extract and arbutin upon kidney function and primary DNA damage in renal cells of rats.

Although strawberry tree (Arbutus unedo L.) leaves have long been used as a herbal remedy, insufficient information is available on their nephrotoxicity. We assessed the safety of strawberry tree water leaf extract and its key component arbutin, administered per os to Lewis rats of both genders at 200 mg/kg b.w./day for 14 and 28 days. The effects of the tested compounds on DNA integrity in renal cells was evaluated using alkaline comet assay, while kidney function was studied using serum creatinine and urea levels. Strawberry tree water leaf extract showed high biocompatibility with kidney tissue. It did not impair DNA integrity of renal cells and kidney function, either in male or female rats. However, exposure to single arbutin affected the levels of primary DNA damage in renal cells which could be related to metabolic conversion of arbutin into hydroquinone, whose nephrotoxicity has previously been proven.

High Doses of Δ9-Tetrahydrocannabinol Might Impair Irinotecan Chemotherapy: A Review of Potentially Harmful Interactions.

This review proposes the hypothesis that the effectiveness of irinotecan chemotherapy might be impaired by high doses of concomitantly administered Δ9-tetrahydrocannabinol (THC). The most important features shared by irinotecan and THC, which might represent sources of potentially harmful interactions are: first-pass hepatic metabolism mediated by cytochrome P450 (CYP) enzyme CYP3A4; glucuronidation mediated by uridine diphosphate glycosyltransferase (UGT) enzymes, isoforms 1A1 and 1A9; transport of parent compounds and their metabolites via canalicular ATP-binding cassette (ABC) transporters ABCB1 and ABCG2; enterohepatic recirculation of both parent compounds, which leads to an extended duration of their pharmacological effects; possible competition for binding to albumin; butyrylcholinesterase (BChE) inhibition by THC, which might impair the conversion of parent irinotecan into the SN-38 metabolite; mutual effects on mitochondrial dysfunction and induction of oxidative stress; potentiation of hepatotoxicity; potentiation of genotoxicity and cytogenetic effects leading to genome instability; possible neurotoxicity; and effects on bilirubin. The controversies associated with the use of highly concentrated THC preparations with irinotecan chemotherapy are also discussed. Despite all of the limitations, the body of evidence provided here could be considered relevant for human-risk assessments and calls for concern in cases when irinotecan chemotherapy is accompanied by preparations rich in THC.

Cigarette Smoking during Pregnancy: Effects on Antioxidant Enzymes, Metallothionein and Trace Elements in Mother-Newborn Pairs.

The effect of maternal smoking as a source of exposure to toxic metals Cd and Pb on superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, metallothionein (MT), Cd, Pb, Cu, Fe, Mn, Se and Zn concentrations were assessed in maternal and umbilical cord blood and placenta in 74 healthy mother-newborn pairs after term delivery. Sparse discriminant analysis (SDA) was used to identify elements with the strongest impact on the SOD, GPx and MT in the measured compartments, which was then quantified by multiple regression analysis. SOD activity was lower in maternal and cord plasma, and higher in the placenta of smokers compared to non-smokers, whereas GPx activity and MT concentration did not differ between the groups. Although active smoking during pregnancy contributed to higher maternal Cd and Pb concentrations, its contribution to the variability of SOD, GPx or MT after control for other elements identified by SDA was not significant. However, an impaired balance in the antioxidant defence observed in the conditions of relatively low-to-moderate exposure levels to Cd and Pb could contribute to an increased susceptibility of offspring to oxidative stress and risk of disease development later in life. Further study on a larger number of subjects will help to better understand complex interactions between exposure to toxic elements and oxidative stress related to maternal cigarette smoking.