Journal of Toxicology

The present work was carried out to investigate the toxic effects of Activated Curcumin C3 Complex (AC³®) through the methods of acute, subacute, subchronic, reproductive/developmental toxicity, and genotoxicity when administered orally in experimental rodents. The studies were carried out in line with OECD principles of good laboratory practice. A single-dose acute oral toxicity study was conducted on female Wistar rats that produced no toxic effects after 14 days (the observation period) of treatment. Subacute, subchronic, and reproductive/developmental studies were conducted in Wistar rats, divided equally into vehicle control, 125, 250, and 500 mg/kg dose groups along with recovery groups for vehicle control and high dose. In all the studies, there were no abnormal clinical signs/behavioral changes, reproductive and developmental parameters, or gross and histopathological changes. Likewise, no alteration was found in the body weight, hematology, and other biochemical parameters. Also, it did not show mutagenicity in the in vitro AMES test or clastogenicity and aneugenicity in the in vivo micronucleus test, indicating that AC³® did not induce any genotoxic effects. This revealed that oral administration of AC³® is safe in rodents, nonmutagenic, and had no observed adverse effects under experimental conditions.

Harmful algal blooms (HABs) pose a significant threat to aquatic ecosystems and human health due to the production of toxins. The identification and quantification of these toxins are crucial for water quality management decisions. This study used DNA analysis (PCR techniques) to identify toxin-producing strains and liquid-chromatography-tandem mass spectrometry (LC-MS/MS) to quantify microcystins in samples from Mindu and Nyumba ya Mungu Dams in Tanzania. The results showed that HABs were detected in both dams. The BLAST results revealed that the 16S gene sequences of uncultured samples were very similar to an Antarctic cyanobacterium, Leptolyngbya sp, Anabaena sp, and Microcystis aeruginosa. Sequences of the cultured samples were most similar to Nodularia spumigena, Amazoninema brasiliense, Anabaena sp, and Microcystis aeruginosa. Further analyses showed that the nucleotide sequence similarity of uncultured isolates from this study and those from the GenBank ranged from 85 to 100%. For cultured isolates from this study and others from the GenBank, nucleotide identity ranged from 81 to 100%. The molecular identification of Microcystis aeruginosa confirmed the presence of HABs in both Mindu and Nyumba ya Mungu Dams in Tanzania. At Mindu Dam, the mean concentrations (± standard deviation) of microcystin-LR, -RR, and -YR were 1.08 ± 0.749 ppm, 0.120 ± 0.0211 ppm, and 1.37 ± 0.862 ppm, respectively. Similarly, at Nyumba ya Mungu Dam, the concentrations of microcystin-LR, -RR, and -YR were 1.07 ± 0.499 ppm, 0.124 ± 0.0224 ppm, and 0.961 ± 0.408 ppm, respectively. This paper represents the first application of PCR and LC-MS/MS to study microcystins in small freshwater reservoirs in Tanzania. This study confirms the presence of toxin-producing strains of Microcystis aeruginosa in both dams and also provides evidence of the occurrence of microcystins from these strains. These findings contribute in improving the monitoring of HABs contamination and their potential impact on water quality in Tanzanian reservoirs.

Sodium metabisulfite (SMB) is a biocide and antioxidant agent generally used as a preservative in food and beverage industries but can oxidize to harmful sulfite radicals. A standardized Ginkgo biloba (EGb-761) has demonstrated potent antioxidant and anti-inflammatory activities, which is beneficial for the treatment of diseases that exhibit oxidative stress and inflammation. The present study sought to investigate the putative ameliorative effects of EGb-761 against SMB-induced toxicity in mice. Thirty-two male Swiss white mice were randomized into control, SMB-treated, SMB + EGb-761-treated, and EGb-761-treated groups. EGb-761 (100 mg/kg/day) and SMB (98 mg/kg/day) were administered by gastric gavage for 40 days. Oral administration of EGb-761 restored SMB-induced decrease in body weight and prevented SMB-induced thrombocytopenia, leukocytosis, and anemia. Furthermore, EGb-761-treatment protected against SMB-induced liver and kidney injury depicted by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, creatinine, urea, uric acid, and albumin. Furthermore, EGb-761 treatment attenuated SMB-driven dyslipidemia and metabolic acidosis. Besides, EGb-761 supplementation abrogated SMB-driven oxidative stress as depicted by stabilized reduced glutathione (GSH) levels in the brain, liver, kidney, spleen, heart, and lungs. SMB induced a significant increase of tissue levels of malondialdehyde (MDA), serum nitric oxide (NO), interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) which were abrogated by EGb-761 treatment. In conclusion, these results deepen our understanding of EGb-761 in light of various detrimental effects of SMB-driven toxicities. These findings provide a novel approach that can be optimized for preventing or treating exposure due to SMB toxicity.

Soy leghemoglobin (LegH) protein derived from soy (Glycine max) produced in Pichia pastoris (reclassified as Komagataella phaffii) as LegH Prep is a novel food ingredient that provides meat-like flavor and aroma to plant-derived food products. The safety of LegH Prep has been previously assessed in a battery of in vivo and in vitro testing and found no adverse effects under the conditions tested. In this new work, we present the results of new in vivo and in vitro tests evaluating the safety of LegH Prep. LegH Prep was nonmutagenic in a bacterial reverse mutation assay and nonclastogenic in an in vitro micronucleus assay in human lymphocytes. Systemic toxicity was evaluated in the 90 day dietary study in male and female Sprague–Dawley® rats that included a 28 day recovery period. The study resulted in no animal deaths associated with the administration of LegH Prep at the highest dose (90,000 ppm). There were no significant adverse clinical or physical changes attributed to LegH Prep administration, and no observed adverse effects on either male or female rats over the course of the 28 day recovery phase study. The new 90 day dietary toxicity study established a no observed adverse effect level (NOAEL) of 4798.3 and 5761.5 mg/kg/day, the maximum level tested for male and female rats, respectively. Thus, the results of the studies demonstrate that under the conditions tested, LegH Prep is not toxic for consumption in meat analog products.

Objectives. The creation of new herbal medicines for their use in dentistry is relevant. The purpose of this work is to study the acute toxicity of the anticaries dental gel (ACDG3) developed by us based on Origanum vulgare. Results. In case of studying the safety of anticaries dental gel “ACDG3” in animals, that with a single dose of up to 2000 mg/kg, the absence of pathological changes in the behavior of animals was noted. Biochemical studies indicate that the studied doses of dental gel did not lead to significant deviations in the blood parameters of mice and deviations fluctuated within the reference values. According to the results of a morphometric study conducted 15 days after the administration of the drug, no deviations were found. The histological evaluation of organs showed little change in the cardiac architecture in animals treated with ACDG3 at doses of 1000 mg/kg and 2000 mg/kg. On the other hand, no significant changes in the cardiac function were observed in all treated mice. Conclusion. As follows from the results obtained, in case of determining acute toxicity, the studied anticaries gel, ACDG3, showed low toxicity. For mice, LD50 was 2000 mg/kg intragastrically. So, according to the generally accepted classification of the toxicity of substances, ACDG3 can be attributed to the class of low-toxic substances (IV class of toxicity, LD50 > 5000 mg/kg, intragastric administration), that is, to practically nontoxic compounds.

Imidacloprid (IMI) is a neonicotinoid insecticide used worldwide, either alone or in combination with other pesticides. The goal of this study was to assess the effects of IMI on the central nervous system of rats and its mechanism of oxidative stress-induced DNA damage by oxidant/antioxidant parameters. Fifteen male rats, divided into three groups, were used: the first group received 5 ml/kg body weight corn oil as a control, the second received a high oral dose of IMI (45 mg/kg body weight), while the third received a low dose (22 mg/kg body weight). After 28 days, acetylcholinesterase (AChE) activity, oxidative stress markers, histopathological alterations, and DNA damage were examined in the brains of these rats. The AChE activities decreased significantly after IMI exposure, reaching 2.45 and 2.75 nmol/min/mg protein in high dose and low dose, respectively, compared to the control group (3.75 nmol/g tissues), while the concentration of malondialdehyde MDA increased significantly (29.28 and 23.92 nmol/g tissues) vs. the control group (19.28 nmol/g tissues). The antioxidant status parameters such as reduced glutathione (GSH) content was 13.77 and 17.63 nmol/g, catalase (CAT) activity was 22.56 and 26.65 µmol/min/g, and superoxide dismutase (SOD) activity was 6.66 and 7.23 µmol/min/g in both doses against the control group (21.37 nmol/g, 30.67 µmol/min/g, 11.76 µmol/min/g), respectively, and histopathological changes in the brain tissues were observed. More in vivo research using epigenetic methods is needed to determine the ability of IMI and its metabolites to cause neurotoxicity and DNA lesions in mammalian brains.