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.

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.

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 Δ⁹-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.

Besides its neurotoxic action and selective toxicity on insecticidal nicotinic acetylcholine receptors, recent studies have shown that imidacloprid may cause other adverse effects in mammals. In the present study, cholinesterase activity, oxidative stress response, genotoxicity in the liver and kidney, and imidacloprid levels in the urine, liver, and kidney of male Wistar rats orally administered with 0.06, 0.8, and 2.25 mg imidacloprid/kg bw/day for 28 days were evaluated. Imidacloprid urine mass concentrations in treated rats increased dose-dependently. Exposure to 0.8 mg imidacloprid/kg bw/per day significantly decreased cholinesterase activities in the liver and kidney. Reactive oxygen species levels decreased significantly in the liver at the same dose. Lipid peroxidation was significantly reduced in the liver at two higher doses. No significant changes in glutathione levels or the activities of superoxide dismutase and catalase were observed. A significant decrease in the activity of glutathione peroxidase was detected in the liver at the highest dose. DNA damage was low in both liver and kidney. Exposure to imidacloprid at studied experimental conditions did not cause a significant oxidative stress response and resulted in low genotoxic effects in the liver and kidney of rats, indicating that these organs are less susceptible to adverse imidacloprid effects at such low doses.