Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2',3'-dideoxyinosine (ddI) is one of several purine analogues used for the treatment of HIV and the acquired immunodeficiency syndrome (AIDS). These nucleoside analogues are promising in their inhibition of viral reverse transcriptase and termination of DNA synthesis. However, each of these drugs has toxicity associated with its use. A previous immunotoxicological evaluation of 2',3'-dideoxyadenosine (ddA), the parent compound of ddI, showed that ddA suppresses humoral immunity. These studies were undertaken to determine the potential for immunotoxicity due to treatment with ddI. This evaluation included an assessment of innate and acquired immunity after exposure to ddI (100, 250, 500, and 1000 mg/kg/day) for 14, 28 or 180 days. There were no overt signs of toxicity related to treatment with ddI except for a decrease in body weight in the group treated with the highest dose of ddI for 180 days. Overall, 6 months of treatment with ddI showed minimal effects on specific organs with the exception of the spleen and thymus. ddI selectively targets the immune system, with assays that challenge humoral immunity being more affected than those testing cell-mediated immunity. Innate immunity was unaffected by ddI treatment. Cell-mediated immunity, as measured by proliferative response to allogeneic cells (MLR) and the T cell mitogen (Concanavalin A), was moderately suppressed. There were no ddI associated effects on NK function or macrophage function as measured by the vascular clearance rate and phagocytic uptake of the tissue macrophages. The most sensitive indicator of ddI-induced immunotoxicity is suppression of the response to the T-dependent antigen, sheep red blood cells (sRBC). The No Observable Adverse Effect Level (NOAEL) for toxicity to the immune system following 14 days of exposure to ddI is 250 mg/kg. A suppression of the humoral immune response was seen at the lowest dose tested after treatment for 28 and 180 days. Thus, the NOAEL for both of these treatment periods is below 100 mg/kg/day.
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PMID:Immunotoxicity of 2',3'-dideoxyinosine in female B6C3F1 mice. 929 77

Cytokines and IgM levels are important parameters in the acquired immunity of fish. In the present study, the effect of pentachlorophenol (PCP) on the expression of proinflammatory cytokines, TNF-alpha (tumor necrosis factor-alpha) and IL-1beta (interleukin 1) mRNA levels of crucian carp, were determined by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. To put the deduction of PCP's immunotoxicity on B cell function, B cells secretion of IgM under exposure of PCP-administrated fish macrophage was determined by enzyme-linked immunosorbent assay (ELISA), and the ability of B cells to secrete IgM was determined by enzyme-linked immunospot (ELISPOT). The results showed that the mRNA expressions of these two cytokines were suppressed by the administration of PCP. The supernatants from PCP-administrated fish macrophage showed less stimulation on B cell, lower maturation of B cells and secretion of IgM. These results suggested that PCP might have impact on micromilieu immune factors as proinflammatory cytokines.
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PMID:Pentachlorophenol reduces B lymphocyte function through proinflammatory cytokines in Carassius auratus. 1562 36

Nevirapine (NVP) is a first-generation non-nucleoside reverse transcriptase inhibitor widely used for the treatment and prophylaxis of human immunodeficiency virus infection. The drug is taken throughout the patient's life and, due to the availability of an extended-release formulation, it is administered once daily. This antiretroviral is one of the scarce examples of drugs with prescription criteria based on sex, in order to prevent adverse reactions. The therapy with NVP has been associated with potentially life-threatening liver and idiosyncratic skin toxicity. Multiple evidence has emerged regarding the formation of electrophilic NVP metabolites as crucial for adverse idiosyncratic reactions. The formation of reactive metabolites that yield covalent adducts with proteins has been demonstrated in patients under NVP-based treatment. Interestingly, several pharmacogenetic- and sex-related factors associated with NVP toxicity can be mechanistically explained by an imbalance toward increased formation of NVP-derived reactive metabolites and/or impaired detoxification capability. Moreover, the haptenation of self-proteins by these reactive species provides a plausible link between NVP bioactivation and immunotoxicity, further supporting the relevance of this toxicokinetics hypothesis. In the current paper, we review the existing knowledge and recent developments on NVP metabolism and their relation to NVP toxicity.
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PMID:Singularities of nevirapine metabolism: from sex-dependent differences to idiosyncratic toxicity. 3071 1