Rhizophora Mucronata Lam. (Mangrove) Bark Extract Prevents Ethanol-induced Liver Injury, Oxidative Stress and Apoptosis in Swiss Albino Mice

The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication. An oral administration of different concentrations (100, 200, and 400 mg/kg) of BERM prior to high-dose ethanol via intraperitoneal injection was performed in mice. On the 7th day, liver and kidney sections were dissected out for histopathological examination. The ethanol intoxication caused large areas of liver necrosis while the kidneys were not affected. Pre-BERM administration decreased ethanol-induced liver injury, as compared to the mice treated with ethanol alone. In addition, the pre-BERM administration resulted in a decrement in the level of ethanol-induced oxidative stress, revealed by a concomitant increase of GSH and a decrease of MDA hepatic levels. The BERM extract also reversed the ethanol-induced liver injury and hepatotoxicity, characterized by the low detection of TNF-α gene expression level and fragmented DNA, respectively. Altogether, BERM extract exerts antioxidative activities and present promising hepatoprotective effects against ethanol intoxication. The identification of the related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.

Fast maturation of splenic dendritic cells upon TBI is associated with FLT3/FLT3L signaling

Systemic inflammatory consequences remain a significant burden after traumatic brain injury (TBI), with almost all organs affected. The spleen is connected with the brain by autonomic innervation and by soluble mediators, and the cross-talk between brain and spleen may be important to establish the systemic inflammatory response to TBI. Ethanol intoxication, the most common comorbidity of TBI, is posited to influence the peripheral inflammatory response either directly or through the brain-spleen cross-talk. Here we show that TBI causes a substantial change in transcription of genes associated with dendritic cells activation in the spleen, in particular a FLT3/FLT3L induction 3h after TBI, which was enhanced by EI. The FLT3L induction was associated with the phosphorylation of FLT3 receptor in CD11c+ dendritic cells, which enhanced the protein synthesis of a subset of mRNAs, as shown by the increase in pS6, peIF2A levels in dendritic cells. This corresponded to the upregulation of proteins associated with maturation process and immunostimulatory properties such MHC-II, LAMP1 and CD68, and of pro-inflammatory cytokines such as TNFα. Notably, EI enhanced the maturation of dendritic cells. However, whereas TBI decreases expression of the adrenergic 2b receptors on dendritic cells, EI increased it, thus augmenting the chances of cross-talk regulation of immune function by the autonomic system. In conclusion, this data indicates that TBI induces a fast maturation of the immunomodulatory functions of dendritic cells which is associated by FLT3/FLT3L signaling and which is enhanced by EI prior to TBI.

Methods of forensic medical analysis of acute intoxications with ethyl alcohol (review of literary sources)

The article presents an overview of current literature on the problem of forensic diagnosis of acute poisoning by ethanol and its surrogates. Morphological and forensic chemical criteria for the diagnosis of ethanol intoxication are presented, variants of patho- and thanatogenesis are described, as well as modern methods for diagnosing these poisonings. Aim of the work. Review of current literature data on the problem of forensic diagnosis of acute poisoning by ethanol and its surrogates. Conclusion. In our opinion, it is necessary to introduce into the practical work of the bureau of forensic examinations new promising technologies for the diagnosis of acute intoxication with ethyl alcohol and its surrogates.

Extremely dilution of Strychnos Nux vomica mitigates alcohol-induced reduction in enthalpies associated with free water molecules in fish brain

Background: Alcoholism is a global health problem. Extract of the seeds of Strychnos Nux vomica and its high dilution have long been used in homeopathy for alcohol induced diseases of patients. Alcoholism leads to reduced brain volume. Glial cells like astroglia contain large number of water channel proteins or aquaporin (AQP4) which mediate glial oedema resulting from ethanol intoxication. Nux vomica, a homeopathic drug of plant origin, is known to counteract alcohol effect. Aim: The objective of this present study is to find out the level of free water molecules in the brain of a teleost fish under ethanol intoxication. The other purpose is to determine whether Nux vomica could restore the level of free water in the alcohol treated fish. Methodology: One group of fish was exposed to 456 mM ethanol for 30 min, another exposed first to a solution of Nux vomica 200c for 20 min and then to 456 mM ethanol for 30 min. The third group served as an untreated control. The mid brain of each fish was kept in an aluminium sample pan and its free water level was assessed by differential scanning calorimetry (DSC). Data were analyzed by ANOVA. Results and discussion: The results show that there was no significant variation in melting and freezing temperature of brain samples but the enthalpies, both freezing and melting varied significantly (P

N-acetylcysteine relieves neurologic signs of acute ethanol hangover in rats

Introduction: Alcohol abuse is one of the grave social and medical problems in many countries, including Russia. Alcohol not only negatively affects health, social and family relationships, but also a person’s performance. Hangover, which is a one of the negative consequences of alcohol intake, is a complex of neurological and somatic symptoms that occur when ethanol is almost completely metabolized to acetaldehyde. This condition, despite the severity and potential economic damage, remains poorly understood, and there are no effective medicines to treat it. Aim: to provide an experimental basis for the possibility of using N-acetylcysteine (NAC), a precursor of glutathione, as a medicine for prevention of the neurological and cognitive impairments due to alcohol intoxication. Materials and Methods: The study used male Wistar rats, which were intraperitoneally injected with ethanol at a dose of 3 g/kg to simulate acute ethanol intoxication. Sixty minutes before the injection, the animals from the experimental groups were gavaged with NAC (1 g/kg) or with an equivalent volume of saline. Immediately after awakening and 3 h after it, the animals were assessed for neurological deficits, motor skills, spontaneous motor activity, and cognitive functions. After the completion of the behavioral tests, the animals were euthanized to assess the level of glutathione, triglycerides (TGs), and malonic dialdehyde (MDA) in liver homogenates, and to determine the activity of enzymatic antioxidant systems and serum aminotransferases. Results and Discussion: The ethanol intoxication in the animals from the control group was associated with pronounced signs of neurological and cognitive impairments, including low spontaneous motor and exploratory activity, impaired fine motor skills in the adhesive test, and cognitive function decline in the Morris water maze test. The rats which had received NAC before ethanol injection demonstrated better fine motor skills in the adhesive test, a higher level of spontaneous motor activity and better performance in the Morris water maze test (in comparison to the animals treated with saline before alcohol intoxication). In the animals which had received NAC, the levels of glutathione, MDA, and TGs, as well as the activity of liver antioxidant enzymes, were closer to the values of the intact rats to a greater extent than in the animals that had been injected with ethanol and received saline. Conclusion: Orally administered NAC before acute ethanol intoxication led to a decrease in the severity of neurological deficiency in rats and reduced the amnesic effect of ethanol. This could be due to an improvement of ethanol metabolism and a decrease in the severity of disorders associated with oxidative stress and liver dysfunction.

Morphometric features of rat pinealocytes in conditions of chronic ethanol intoxication

Ethanol has chronobiological effects, which are associated with inhibition of melatonin synthesis and secretion and disruption of the sleep-wake cycle. Ethanol is known to cause sleep fragmentation due to frequent awakenings, prolong wakefulness, and reduce the duration of the slow sleep phase. At the same time, changes in the morphology of the pineal gland under chronic exposure to ethanol remain poorly studied. Of particular interest are changes in the basic morphometric parameters of pinealocytes, because they are a marker of the functional state of the pineal gland. The aim of the study was to morphometrically study the features of morphological changes in rat pinealocytes in the physiological norm and in chronic ethanol intoxication. To achieve this goal, we used 20 laboratory male rats: a control group and an experimental group. The control group was under standard vivarium conditions. For the experimental group, alcohol intoxication was modeled by injecting a 40% ethanol solution at the rate of 12 mg/kg of body weight intragastric 4 times a day. The morphometric parameters of pinealocytes were studied on day 30 from the start of the study. According to the results of morphometric measurements, a significant increase in the parameters of light pinealocytes and a decrease in the parameters of dark cells were established. It was determined that the average values of the cytoplasm area of light pinealocytes increase by 54.55% (p<0.05), the area of the nucleus increases by 61.32% (p<0.05), and the area of the nucleolus by 32.84% (p<0.05) compared with the control group. The area of the cytoplasm of dark pinealocytes decreases by 27.2% (p<0.05), and the area of the nucleus by 37.33% (p<0.05). Changes in the ratio of light and dark pinealocytes were also noted. An increase in the number of active light cells by 8.17% was found. The detected morphometric changes indicate high functional activity of cells, which has a compensatory nature in response to apoptosis of pinealocytes.