The role of pathology in the identification of drug-induced hepatic toxicity
Pathologists play a central role in the recognition and prevention of drug-induced toxicity. Pathologists engaged in clinical practice must identify a pattern of histological lesions that are interpreted in concert with a variety of clinical data to determine the probability of drug-induced toxicity versus background disease processes and the most likely drug, often of many, to have caused the specific injury. Toxicological pathologists, working in concert with other scientists, have the responsibility of preventing drug-induced toxicity in humans by identifying potentially toxic drugs and keeping them from the marketplace. In this process of drug development, a broad array of in vivo testing using a number of animal species and in vitro assays are used. Technological advances require pathologists to integrate molecular-based mechanistic data effectively with traditional morphological evaluation to develop a more detailed grasp of the pathogenesis of drug-induced injury. All pathologists have the responsibility to effectively and accurately communicate their findings and interpretations to the appropriate audiences.
- "Drug/chemical-mediated hepatic injury is the most common manifestation of drug toxicity and accounts for greater than 50% of acute liver failure cases. Hepatic damage is the largest obstacle to the development of drugs and is the major reason for withdrawal of drugs from the market (Cullen and Miller, 2006). "
[Show abstract] [Hide abstract] ABSTRACT: Cancer is one of the leading causes of death around the world. Tumor-targeted drug delivery is one of the major areas in cancer research. Aptamers exhibit many desirable properties for tumor-targeted drug delivery, such as ease of selection and synthesis, high binding affinity and specificity, low immunogenicity, and versatile synthetic accessibility. Over the last several years, aptamers have quickly become a new class of targeting ligands for drug delivery applications. In this review, we will discuss in detail about aptamer-based delivery of chemotherapy drugs (e.g. doxorubicin, docetaxel, daunorubicin, and cisplatin), toxins (e.g. gelonin and various photodynamic therapy agents), and a variety of small interfering RNAs. Although the results are promising which warrants enthusiasm for aptamer-based drug delivery, tumor homing of aptamer-based conjugates after systemic injection has only been achieved in one report. Much remains to be done before aptamer-based drug delivery can reach clinical trials and eventually the day-to-day management of cancer patients. Therefore, future directions and challenges in aptamer-based drug delivery are also discussed.0Comments 33Citations
- "This vicious cycle of large doses and the concurrent toxicity is a major limitation of current cancer therapy. Sometimes patients succumb to the adverse effects of the drug far earlier than the tumor burden [21,22]. Therefore, the development of an effective drug delivery strategy can significantly improve metastatic cancer patient management. "
[Show abstract] [Hide abstract] ABSTRACT: Assessing liver damage in basic toxicology research and in preclinical toxicity testing is usually evaluated by serum biochemical parameters prior to confirmation by histopathology. With the advent of newer methods such as genomics and proteomics, there is increased enthusiasm to generate "novel" predictive markers to detect liver pathology even before the alterations in clinical and histopathology parameters occur. However, serum biochemical parameters (clinical pathology) when employed accurately, can provide important and useful information in assessing not only the extent and severity of liver damage, but also the type of liver damage (membrane injury versus cholestasis and hepatic function). In order to accurately detect hepatobiliary pathologies, it is important to have a basic understanding of liver associated clinical pathology parameters with reference to their exact location, serum half-lives, tissue concentration gradient and species differences. Such understanding as discussed in this article will enable a toxicologist to identify commonly encountered toxic hepatic lesions such as necrosis, cholestasis and compromised liver function by hepatic-associated clinical pathology parameters. In addition, toxicologists will have a better grasp to effectively communicate their clinical pathology findings and interpretations to the target audiences.0Comments 125Citations
- "Thus, this article will review the role of serum biochemical parameters in the detection of drug-induced liver toxicity. Although drug/chemical-mediated liver toxicity is not restricted to a few histologic patterns (Cullen and Miller, 2006; Zimmerman, 1998), liver injury can be classified as @BULLET Acute or chronic hepatitis/cholestatis depending on the persistence of injury and nature of inflammatory cells. Accordingly, acute (neutrophilic) and chronic (macrophages/lymphocytic ) hepatitis/cholestasis is recognized. "