Antinociceptive activities of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol, and its possible mechanisms of action in mice

A novel synthetic compound from the 2-benzoyl-6-benzylidenecyclohexanone analogue, namely 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC), showed pronounced nitric oxide inhibition in IFN-γ/LPS-induced RAW 264.7 cells. Based on this previous finding, our present study aimed to investigate the antinociceptive effects of BBHC via chemical and thermal stimuli in vivo. The investigation of the antinociceptive activity of BBHC (0.1, 0.3, 1.0 and 3.0 mg/kg, i.p.) was initiated with 3 preliminary screening tests, then BBHC was subjected to investigate its possible involvement with excitatory neurotransmitters and opioid receptors. The potential acute toxicity of BBHC administration was also studied. Administration of BBHC significantly inhibited acetic acid-induced abdominal constrictions, formalin-induced paw licking activity and developed notable increment in the latency time. BBHC’s ability to suppress capsaicin- and glutamate-induced paw licking activities, as well as to antagonise the effect of naloxone, had indicated the possible involvement of its antinociception with TRPV1, glutamate and opioid receptors, respectively. The antinociceptive activities of BBHC was not related to any sedative action and no evidence of acute toxic effect was detected. The present study showed that BBHC possessed significant peripheral and central antinociceptive activities via chemical- and thermal-induced nociceptive murine models without any locomotor alteration and acute toxicity.

Bioavailability and Safety of Lipid Fraction from Different Taxa of Microalgae in Female C57BL/6 Mice

Microalgae exhibit antioxidant, anti-inflammatory effects. In this study, we analyzed the toxicity of lipid fraction of different taxa of microalgae in female C57BL/6 mice. The number of red blood cells, white blood cells and subsets, hemoglobin, number, and functional activities of immature and mature immunocytes, biochemical parameters in blood serum, and kidney and liver extract were investigated. It is shown that the lipid fraction of microalgae had no acute toxic effect on body weight, glucose blood levels, and hemopoiesis in mice. Some changes in the number of immature and mature lymphocytes, proliferative potential, Ig levels, cytokine production were determined. In vivo lipid fraction of microalgae caused changes in cytokine, protein, lipid, purine, aminotransferases, and sex hormone level in mice. Obtained data indicate that lipid fraction dietary administration in female C57BL/6 mice does not have a toxic effect on the animal.

Study of early metabolic changes in experimental animals with acute toxic exposure to paracetamol and against the background of correction

Paracetamol is one of the most widely used and popular over-the-counter analgesics and antipyretic drugs in the world. The number of registered cases of paracetamol-induced liver intoxication is constantly increasing in the world every year. It seems relevant to study early metabolic disorders in the liver in acute paracetamol intoxication and assess the effectiveness of the timely use of hepatoprotective drugs. The aim of this research is to study metabolic changes in laboratory animals at the early stages of exposure to paracetamol and against the background of correction with oxymethyluracil, ademetionine and mexidol. An experimental study of metabolic changes in laboratory animals under acute exposure to toxic doses of paracetamol and against the background of correction was carried out. Biochemical parameters in the blood serum of laboratory animals were investigated. The obtained results showed that the intake of paracetamol in toxic doses was accompanied by impaired hepatic metabolism at the earliest stages of exposure. With the corrective action of the studied drugs, metabolic disturbances caused by paracetamol intoxication were restored. At the same time, OMU, as well as ademetionine and ethylmethylhydroxypyridine succinate, is able to normalize metabolic changes after the acute toxic effect of paracetamol, and has a pronounced advantage in terms of the protein-synthetic function of hepatocytes.

Determination of acute toxicity of the ‘Bondarmin’ disinfectant when administered intraperitoneally to laboratory animals

The article presents the results of the study of the acute toxic effect of the innovative disinfectant ‘Bondarmin’ (active substance — potassium peroxomonosulfate) on laboratory animals (mice, rats) are presented. Many scientific works of scientists in recent years have been devoted to the study of the toxicity of various disinfectants both in our country and abroad. However, today there are many topical issues regarding the toxicity and safety of some antimicrobials. Our work aimed to study the toxic effect on the laboratory animals and to establish the acute toxicity (LD50) of the developed disinfectant ‘Bondarmin’ when administered intraperitoneally. Experiments were carried out in the Laboratory of Pharmacology and Toxicology of the National University of Pharmacy (Kharkiv) and in the Educational and Scientific Laboratory of Genetic and Molecular Research Methods named after P. I. Verbitskiy in the Kharkiv State Zooveterinary Academy. Acute toxicity assessment (LD50) was carried out with intraperitoneal administration of the designed disinfectant to laboratory animals (mice, rats). The toxic effect of the newly developed disinfectant ‘Bondarmin’ for the intraperitoneal method of administration to laboratory animals (mice, rats) has been determined. For the intraperitoneal administration of the ‘Bondarmin’ disinfectant, the LD50 by Prozorovskiy method is 316.85 ± 19.26 mg/kg for mice, and 279.33 ± 19.80 mg/kg for rats. The disinfectant belongs to the IV toxicity class (low toxic substances). The results of toxicological studies allow us to recommend the use of ‘Bondarmin’ for disinfecting livestock facilities

Glucocorticoids in Freshwaters: Degradation by Solar Light and Environmental Toxicity of the Photoproducts

The photodegradation process of seven glucocorticoids (GCs), cortisone (CORT), hydrocortisone (HCORT), betamethasone (BETA), dexamethasone (DEXA), prednisone (PRED), prednisolone (PREDLO) and triamcinolone (TRIAM) was studied in tap and river water at a concentration close to the environmental ones. All drugs underwent sunlight degradation according to a pseudo-first-order decay. The kinetic constants ranged from 0.00082 min−1 for CORT to 0.024 min−1 for PRED and PREDLO. The photo-generated products were identified by high-pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The main steps of the degradation pathways were the oxidative cleavage of the chain 17 for CORT, HCORT and the rearrangement of the cyclohexadiene moiety for the other GCs. The acute and chronic toxicity of GCs and of their photoproducts was assessed by the V. fischeri and P.subcapitata inhibition assays. The bioassays revealed no significant differences in toxicity between the parent compounds and their photoproducts, but the two organisms showed different responses. All samples produced a moderate acute toxic effect on V. fisheri and no one in the chronic tests. On the contrary, evident hormesis or eutrophic effect was produced on the algae, especially for long-term contact.

Cadmium distribution and metallothionein expression in rat organs following acute intoxication

Introduction. This article presents the results of experimental simulation of the acute toxic effect of cadmium on the rat organism, its distribution in the liver, and kidneys. Activation of the protective mechanism against toxic metal through the metallothionein protein has to reduce the bioavailability of free cadmium. Material and methods. The study was conducted on rats weighing 140-190 g, which was once intragastrically injected with cadmium chloride in an amount of 1/20 LD50. We studied the time intervals: before intoxication, 1, 2, 4, 6, 24, 48, and 96 hours after inoculation. The accumulation of cadmium in the liver and kidneys was measured by atomic absorption spectrometry. The expression of the metallothionein gene (МТ1, МТ2А, МТ3) was determined using RT-PCR on RNA isolated from the same organs. Results. Quantitative differences in the metal content in the liver and kidneys are observed 1 hour after intoxication, with a cadmium content of 250 and 125 times higher than in the control groups, respectively. There is an accumulation of cadmium in the liver with a maximum after 6 hours, and then its redistribution to the kidneys. The pronounced expression of metallothionein with a single acute exposure to cadmium is tissue-specific, so the expression of the MT1 and MT2A genes was greatest in the liver and the MT3 gene in the kidneys. Discussion. After administration cadmium is mainly localized in hepatocytes and its concentration may exceed the ability of metallothionein to bind cadmium ions, which leads to histopathological changes in the liver. In response to the intake of metal in the cell, the expression pattern of many genes, including those associated with the activation of protective reactions, changes. Conclusion. Our data show a single exposure to cadmium to lead to an increase in the content of MT transcript in the liver and kidneys, simultaneously with the accumulation of metal in them. The nature of this accumulation depends on the organ, on the time of exposure, and gene expression also on the form of MT.

Ethnobotanical Survey and In vivo Assessment of the Antimalarial Activities of a Locally Used Medicinal Plant (Senna occidentalis) for “Malaria Suspected” Fever in Potiskum and Nangere Local Government Areas of Yobe State

Malaria is a life threatening infectious disease that has affected economic development in many parts of the world. Although preventable, malaria has claimed the lives of thousands of individuals in endemic African countries. Antimalarial drug resistance, lack of vaccines in clinical use as well as complexities of malaria parasite genomes remains a serious threat to malaria eradication efforts. The search for antimalarials from plant sources has yield significant success in drug discovery approaches. The specific objective of this study is to establish the acute toxic effect and antiplasmodial efficacy of crude methanolic leaf extract of Senna occidentalis in an in vivo assay. The four (4) days suppressive test was used in Swiss mice experimentally infected with chloroquine sensitive (CQS) Plasmodium berghei (ANKA). Results obtained revealed no lethality nor any sign of acute toxic reactions following the administration of 2000 mg/kg body weight of the extract. Percent reduction of parasite growth obtained was observed to be dose dependent in all groups treated with the herbal extract and ranges between 66% and 73%. Relative to the negative and positive control groups, a significant reduction in parasitaemia (P≤ 0.01) was observed in all groups treated with the plant extracts. A gradual increase in body weight was observed in extract treated groups throughout the period of the investigation. The antiplasmodial efficacy observed may well be attributed to the presence of alkaloids, flavonoids and other important phytochemicals present. S. occidentalis is therefore, considered a good candidate source for development of novel antimalarial drugs.

Aqueous extract of dry powder blend of seeds and leaves of Picralima nitida (Stapf) T. & H. Durand reduce pain and inflammation in animal models

ObjectivesBlend of seeds and leaves of Picralima nitida herein referred to as West African Durand powder (WDP) was investigated for antinociceptive and anti-inflammatory properties.MethodsAcute toxic effect of the aqueous extract was evaluated in mice of both sexes. Antinociceptive effect of WDP (100–400 mg/kg) was evaluated in models of acetic acid-induced writhing and thermal nociception on hot plate in mice. Carrageenan-induced paw oedema and air pouch rat models were used to evaluate the anti-inflammatory activity of the extract.ResultsWDP (2,000 mg/kg) showed no toxic effect in mice. WDP at 100, 200 and 400 mg/kg inhibited abdominal writhings by 59.9, 66.0 and 79.0%, respectively. There was a significant increase in reaction time on the hot plate tests in mice treated with WDP (400 mg/kg). The paw oedema was reduced by WDP (100, 200 and 400 mg/kg) 5 h post-carrageeenan. Exudate volume was significantly reduced to 39.8 and 44.8% by 200 and 400 mg/kg WDP, respectively. WDP reduced Leucocytes counts (23.3 and 57.1%, respectively) and neutrophil counts (28.1 and 60.0%, as well as reduced nitrites, malondialdehyde levels and increased glutathione concentrations in the air pouch.ConclusionsThese results suggest that aqueous extract of blend of seeds and leaves of P. nitida possesses antinociceptive and anti-inflammatory properties.