Current Drug Metabolism - Volume 19, Issue 7, 2018

Background: Risk factors of drug-induced nephrotoxicity include drug overdose, drug-drug interactions and drug-related adverse effects. Since the usage of some nephrotoxic drugs is still unavoidable in the clinical setting, understanding the pathogenic mechanisms of their nephrotoxicities is critical to decrease the incidence of kidney injury. Early detection of drug-induced nephrotoxicity and reduction of the therapeutic side effects are realistic approaches to avoid the end stage of renal failure. Method: In this review, we summarized the mechanisms and prevention strategies for some drugs that were commonly used clinically and had the possibility of inducing acute and chronic kidney injuries. We discussed the advantages and drawbacks of currently available biomarkers for indicating kidney impairment. In vitro and pre-clinical in vivo models for assessing the nephrotoxicity during the drug developmental stages were also evaluated. Results: Nowadays, an increasing number of biomarkers were discovered for the early diagnosis of kidney injury. In addition, various kinds of in vitro and pre-clinical in vivo models were developed and utilized to minimize the potential nephrotoxicity during the drug development. Conclusion: The discovery of the early biomarkers and development of accurate diagnostic methods are effective prevention strategies for drug-induced kidney impairment.

Background: Chronic Kidney Disease (CKD), a global public health problem, affects numerous people worldwide, and the prevalence is rising. Results from animal experiments and clinical investigations have demonstrated that drug metabolic enzymes and transporters-mediated non-renal clearance are dramatically impaired in CKD, co-respondent with alterations in the elimination of metabolized drugs. Accumulated uremic toxins may downregulate or directly inhibit the activity and/or the expression of drug metabolic enzymes and transporters, which may result in unintended alterations of drug exposure and response in cases when drugs dose are not adjusted for the renal dysfunction. Method: The aim of this review is to highlight the impact of CKD on non-renal drug clearance involving metabolism enzyme system and transport pathways, and to provide insight into the impact of non-renal drug clearance on drug metabolism and distribution in CKD patients. Results: Metabolic enzyme system and transport pathways are dysregulated in both rats and humans with renal failure. Conclusion: The alterations of drug metabolic enzymes and transporters in the kidney, liver, and intestine play an important role in their pharmacokinetic changes, and thus, the metabolism and transportation of many medications used to treat CKD patients may be affected.

Background: Kidney dysfunction resulting from various drugs is an important issue during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and animals, and static cell culture experiments cannot fully reflect the actual microphysiological environment in humans. Method: In this review article, authors collected manually relevant bibliographic databases including journal articles and textbooks related to microfluidics, kidney-on-a-chip, and drug screening and interaction. In this review, we discuss recent developments in microfluidic culturing technique and describe current and future kidney-on-a-chip applications. Results: The pharmacodynamic and pathophysiological responses of cells are more realistic in microfluidic or 3D culture systems than in conventional 2D culture systems. Recently, several types of kidney-on-a-chip have been developed that reflect the microenvironment of the kidney tubule and have been shown to better reflect actual in-vivo results of drug nephrotoxicity. Using kidney-on-a-chip, investigators can measure various drug-induced biological responses. In the future, it is expected that a multi-organ chip will be utilized to examine the interaction between kidney and other organs, and kidney-on-a-chip can be used in disease modeling and the development of new renal replacement therapy. Conclusions: Using kidney-on-a-chip, researchers can create experimental environments resembling the physiological environments in human organs and obtain experimental results that better reflect human physiology. Kidney-ona- chip can be used to overcome the drawbacks of traditional animal models and to more effectively identify drug effects, interactions, and drug-induced nephrotoxicity.

Background: There is a long history of traditional medicine for serving the world population. For the prevention and treatment of cancer, herbal remedies have played a significant role. In this review, we have summarized medicinal herbs from the entire world, including India, that are used traditionally for various cancer treatment. Whenever we talk about cancer treatment, medicinal plants always have been on the priority. Objective: In this article, we have summarized the flora used in earlier times and recently identified for pre-clinical anticancer treatment. The present paper is a comprehensive review of different literature sources with discussion being made on the therapeutic value of diverse medicinal herbs in the treatment of various kinds of cancer by using different in vitro cancer cell lines. Countless anticancer plants have been recognized with the help of innovative techniques including isolation and structure elucidation that implement their beneficial effect by increasing the immunity of the body, inducing antioxidant action, endorsing making of shielding enzymes, hindering cancer triggering enzymes and hormones, and exciting DNA restoration mechanism. Conclusion: Finally, we have concluded that Argemone mexicana shows maximum anti-cancer activity on various cancer cell lines in comparison to other medicinal plants.

Background: Nanotechnology exploits materials and devices with a functional organization that has been engineered at the nanometre scale. The application of nanotechnology in neuroscience involves specific interactions with neurons and glial cells. This property is used for delivering drugs and other small molecules (such as genes, oligonucleotides and contrasting agents) across the blood brain barrier (BBB), an important requirement for delivering the drug successfully to the brain. Objective: Nanotechnology based approaches (NBA) favours transcytosis-mediated delivery of nanoparticles to the brain by crossing the BBB. The last five years have witnessed the successful applications of NBA to treat neurological disorders. It is expected that the development of novel NBA will result in important insights on the brain mechanisms, and eventually provide better medical care to patients suffering from neurological disorders. Conclusion: This review introduces the emerging work in this area and summarizes the successful NBA used in recent past for treating various neurological disorders ike Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, meningitis and glioblastoma.

Background: Tripterigium wilfordii glycosides (TWG) demonstrate paramount bioactive effectiveness in the management of many autoimmune diseases. However, its side effects on the hepatic, nephrotic, reproductive, and cardiovascular systems have limited its immense therapeutic potentials. Triptolide (TP) and Celastrol (CL), the leading bioactive as well as toxic constituents of TWG, have been widely studied. This review aims to summarize the key mechanisms that TWG trigger the toxic reactions and the precautionary measures that could prevent and reduce such reactions. Method: We undertook a systemic search of bibliographic databases for peer-reviewed research literature about the toxic mechanisms and pharmacokinetic profiles of TWG. The key points of screened papers were described and combined together to make up whole. Results: Totally 125 papers were referred in this paper, the majority were from Chinese academic associations. It has been reported that reactive oxygen species generation, mitochondrial respiratory chain inhibition, and metabolizing enzyme inhibition are the leading factors of the toxic reactions. The bioactive effects and toxicities of TWG are closely related to its metabolic profiles. It has been confirmed that TP and CL inhibit CYP450 and the transporters. This paper reviews and summarizes the pharmacokinetic parameters of TWG. Antioxidants, polymeric micelle and topical nanoparticle formulations have exhibited potentials in toxicity circumvention. Conclusion: A thorough understanding of the pharmacokinetic and toxicological characteristics of TWG combined with further in-depth study will enhance the efficacy and safety in using TWG, which would augment and improve its clinical application in the future.

Background: The increased use of herbal remedies particularly in patients with kidney diseases indicated the importance of studies, which focused on nephrotoxic plants. Objective: The present study aimed to review and assess the kidney-damaging herbs mentioned in the Persian medicine [PM] books. Method: The main PM books were searched for nephrotoxic herbs and their relevant reformers traditionally proposed for preventing renal damage. PubMed, Scopus and Google Scholar were investigated for evaluation of the scientific evidence relating to the nephrotoxicity of herbs. Results: A total of 64 plants with kidney damage potential and their reformer medicaments were recorded in 7 sources included in this review. Allium schoenoprasum and Marrubium vulgare were the most repeated and emphasized nephrotoxic plants in PM books, but there was no relevant scientific evidence. Despite the lack of clinical studies, some evidence was found for 38% of plants that were related to renal damage. The most repeated reformers for reducing the renal side effects mainly consisted of gum tragacanth, gum Arabic, mastic gum, anise, jujube and honey and some evidence was found for their nephroprotective activities. Conclusion: The present study reviewed and assessed the herbs with adverse renal effects in the main PM books. Some evidence was in line with the potential nephrotoxicity of plants and their reformers. Despite the lack of clinical research for evaluation of their renal damage, the herbs may be focused in term of their nephrotoxicity; and there is a need for further studies on the scientific basis of their nephrotoxicity.