Anti-CYP2E1 polyclonal antibody

Background: Drug pre-exposure attenuates sensitivity to the interoceptive stimulus properties of additional subsequently administered drugs in drug-induced conditioned taste avoidance (CTA) and conditioned place preference (CPP) paradigms. Specifically, nicotine, commonly used in conjunction with other addictive substances, attenuates acquisition of ethanol and caffeine CTAs and morphine-induced CPP. Methods: Because nicotine use is comorbid with a number of substance use disorders, we systematically examined the effects of nicotine pre-exposure on two different conditioning paradigms involving integration of the interoceptive stimulus properties of multiple commonly abused drugs, in male and female rats, designed to examine both the aversive and reinforcing properties of these drugs. Results: Nicotine dose-dependently interfered with acquisition of CTA to passively administered morphine, ethanol, and cocaine, but not lithium chloride, demonstrating that the effects of nicotine are not simply a matter of reduced orosensory processing or an inability to learn such associations. Moreover, nicotine-treated rats required higher doses of drug in order to develop CTA and did not show increased acceptance of the taste of self-administered ethanol compared with saline-treated rats. Conclusions: These data demonstrate that nicotine pre-exposure attenuates sensitivity to the stimulus effects of multiple drugs in two conditioning paradigms, in a manner which is consistent with a reduced ability to integrate the interoceptive properties of abused drugs. Through reducing these stimulus properties of drugs of abuse, concomitant nicotine use may result in a need to increase either the frequency or strength of doses during drug-taking, thus likely contributing to enhanced addiction liability in smokers.

Acute liver failure (ALF) occurs by insufficient detoxification of toxic materials in the liver, generating excess reactive oxygen species (ROS). Mesenchymal stem cell (MSC) therapy can be a promising approach for the treatment of liver diseases including ALF by anti-inflammatory activity and secretion of cytokines associated with tissue regeneration. However, the efficacy of MSC therapy is generally poor, mainly due to a low survival and engraftment of administered cells. In this study, we demonstrated that the enhanced delivery of human adipose-derived stem cells (hADSCs) to the damaged liver by the coating of lipid-conjugated heparin could result in significantly improved recovery from ALF in a mouse model. First, the therapeutic effect of secretomes of hADSCs on acetaminophen (APAP)-induced hepatic cell damage was confirmed regardless of the coating of lipid. conjugated heparin on hADSCs in vitro. Then, the therapeutic effects of lipid-conjugated heparin coated hADSCs (Lip-Hep/hADSC group) were analyzed compared to hADSCs themselves (hADSC group) using an APAP-induced ALF model in vivo. Intravenous administration of hADSCs could lower the elevated serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), but Lip-Hep/hADSC group showed faster decrease in serum levels of AST and ALT to the normal values compared to hADSC group. Enhanced delivery and longer retention of hADSCs in the damage liver by the coating of lipid-conjugated heparin were confirmed by optical imaging of isolated organs using labeled cells and immunofluorescence staining of liver tissue sections against human nuclei. A significantly increased level of human hepatic growth factor (hHGF), a representative secretome from hADSC, significantly reduced levels of macrophage and CYP2E1, implying alleviated inflammatory response, were detected by immunofluorescence staining from Lip-Hep/hADSC group compared to hADSC group. These results well coincided with the improved recovery of the damaged liver from Lip-Hep/hADSC group than hADSC group in histological analysis. Thus, the coating of lipid-conjugated heparin on hADSCs has a great potential to improve the therapeutic effect of cells on the liver injury.