Determination of Ochratoxin-A Detoxification and Antibiotic Resistance Potential of Acinetobacter calcoaceticus

The ochratoxin A (OTA) is a mycotoxin which is present in food products as a contaminant, and it is one of the hazardous toxins causing health risks in animals and humans. One of the main health issues is the damage to kidneys. The most adopted technique used in detoxification of this mycotoxin is biodegradation. In this study, Acinetobacter calcoaceticus isolated from soil samples was used for the detoxification of ochratoxin, and also this study explains the antibiotic resistance potential of this organism. Acinetobacter calcoaceticus was tested to see if they could break down ochratoxin A(OTA). Acinetobacter calcoaceticus was shown to be able to break down OTA among the tested microorganisms. We tested the ability of A. calcoaceticus to degrade OTA in LB medium at 25 and 28°C, with OTA concentrations of 2ppm, 6ppm, and 10ppm. A. calcoaceticus was able to break down OTA from a starting concentration of 10 (g/ml) at these conditions. At 25 and 30°C, A. calcoaceticus removed an average of 0.1005 and 0.0636 (g/ml/h of OTA, respectively, from a medium containing an initial concentration of 10 (g/ml). A. calcoaceticus degraded ochratoxin A significantly during and after the log phase of cell development at both incubation temperatures. The hypothesis is that A. calcoaceticus degraded OTA into an ochratoxin with reduced toxicity. At the same time the potential of this microorganism strain was also measured using susceptibility testing and it showed the potential of development of its resistance. Strains of Acinetobacter calcoaceticus isolated from soil samples were tested for their susceptibility against different unrelated classes of antibiotics. A. calcoaceticus was resistant to multiple antibiotics. In vitro degradation assays were used exposing the toxin to the degrading enzyme or microorganism in a controlled laboratory environment. The degradation of the toxin was monitored using various techniques such as high-performance liquid chromatography (HPLC). The significance of this study is to highlight the capability of the Acinetobacter calcoaceticus in degrading ochratoxin A, so that health risks associated with it can be reduced; also, the antibiotic resistance potential measurement helps in development of optimum antimicrobial strategy

Gastroprotective effect of zafirlukast against indomethacin induced gastric ulcer in rats via PGE2 and anti-inflammatory pathways

Objective(s): To evaluate the gastroprotective potential of zafirlukast against indomethacin-induced gastric ulcers in rats.Materials and Methods: Thirty-two male Wistar rats were included in this study and randomly divided into 4 equal groups (n=8); control (normal) group, indomethacin group, Ranitidine group, and Zafirlukast group. Indomethacin was given as a single oral dose of (20 mg/kg) for the induction of ulcers. Both ranitidine (50 mg/kg) and zafirlukast (20 mg/ kg) were given orally for seven days after inducing the ulcer. All animals were sacrificed by an overdose of anesthesia at the end of the experimental period and their gastric tissues have been collected for histopathological and biological assay. Levels of prostaglandin E2 (PGE2), thiobarbituric acid reactive substances (TBARS), and interleukin 1β (IL-1β ) were measured as well as a histopathological study to evaluate the effect of zafirlukast on gastric tissues.Results: Significant abnormalities were found in both the histological and biochemical parameters of the indomethacin group reflecting the changes seen with gastric ulcers. Significant improvement was found in the Zafirlukast group as reflected by the morphological improvement seen in the gastric tissues. An effect that was associated with an increase in the PGE2 levels along with reductions in IL-1β expression and TBARS concentrations.Conclusion: As per the results of this study, zafirlukast shows promising gastroprotective properties possibly through enhancement of PGE2 levels as well as having anti-inflammatory and anti-oxidant properties

Effects of MS-153 on chronic ethanol consumption and GLT1 modulation of glutamate levels in male alcohol-preferring rats

We have recently shown that upregulation of glutamate transporter 1 (GLT1) in the brain is associated in part with reduction in ethanol intake in alcohol-preferring (P) male rats. In this study, we investigated the effects of a synthetic compound, (R)-(−)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), known to activate GLT1 on ethanol consumption as well as GLT1 expression and certain signaling pathways in P rats. P rats were given 24-hour concurrent access to 15% and 30% ethanol, water and food for five weeks. On week 6, P rats received MS-153 at a dose of 50 mg/kg (i.p.) or a vehicle (i.p.) for five consecutive days. We also tested the effect of MS-153 on daily sucrose (10%) intake. Our studies revealed a significant decrease in ethanol intake at the dose of 50 mg/kg MS-153 from Day 1 through Day 14. In addition, MS-153 at dose of 50 mg/kg did not induce any significant effect on sucrose intake. Importantly, we found that MS-153 upregulated the GLT1 level in the nucleus accumbens (NAc) but not in the prefrontal cortex (PFC). In accordance, we found upregulation of nuclear NFkB-65 level in NAc in MS-153-treated group, however, IkB was downregulated in MS-153-treated group in NAc. We did not find any changes in NFkB-65 and IkB levels in PFC. Interestingly, we revealed that p-Akt was downregulated in ethanol vehicle treated groups in the NAc; this downregulation was reversed by MS-153 treatment. We did not observe any significant differences in glutamate aspartate transporter (GLAST) expression among all groups. These findings reveal MS-153 as a GLT1 modulator that may have potential as a therapeutic drug for the treatment of alcohol dependence

Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings

Herein, we have reviewed the role of glutamate, the major excitatory neurotransmitter in the brain, in a number of neurochemical, -physiological, and -behavioral processes mediating the development of alcohol dependence. The findings discussed include results from both preclinical as well as neuroimaging and postmortem clinical studies. Expression levels for a number of glutamate-associated genes and/or proteins are modulated by alcohol abuse and dependence. These changes in expression include metabotropic receptors and ionotropic receptor subunits as well as different glutamate transporters. Moreover, these changes in gene expression parallel the pharmacologic manipulation of these same receptors and transporters. Some of these gene expression changes may have predated alcohol abuse and dependence because a number of glutamate-associated polymorphisms are related to a genetic predisposition to develop alcohol dependence. Other glutamate-associated polymorphisms are linked to age at the onset of alcohol-dependence and initial level of response/sensitivity to alcohol. Finally, findings of innate and/or ethanol-induced glutamate-associated gene expression differences/changes observed in a genetic animal model of alcoholism, the P rat, are summarized. Overall, the existing literature indicates that changes in glutamate receptors, transporters, enzymes, and scaffolding proteins are crucial for the development of alcohol dependence and there is a substantial genetic component to these effects. This indicates that continued research into the genetic underpinnings of these glutamate-associated effects will provide important novel molecular targets for treating alcohol abuse and dependence

A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

The purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine, and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein, we sought to place the P rat's behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this chapter discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general