Radiological Cases of the Month

Dl, Blowey; Alon, Uri; Hellerstein, Stanley; Ba, Warady; Bp, Wood

doi:10.1001/archpedi.1993.02160340103023

Cited by 2 publications

(2 citation statements)

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“…In contrast to chemically synthetic drugs, most herbal medicines have often been claimed to be non-toxic or generally regarded as safe at the current level of exposure, because of their natural origin and long-term or traditional use as folk medicines. Herbal consumption has sometimes been associated with toxicities of the heart, liver, blood, kidney, central nervous system, and skin and less frequently carcinogenesis [13,[15][16][17][18][19][20][21][22][23][24][25][26]. Both adverse drug reactions and poisoning events associated with the use of herbal medicines have increasingly been reported worldwide [9,[11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Activation of Herbal and Dietary Constituents and Its Clinical and Toxicological Implications: An Update

Zhou¹,

Xue²,

Yu³

et al. 2007

CDM

114

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In recent years, there has been a globally increasing application of herbal medicines and dietary supplements to treat various chronic diseases and to promote health. However, there are increasing clinical reports on the organ toxicities associated with consumption of herbal medicines. This review updates the knowledge on metabolic activation of herbal components and its clinical and toxicological implications. Like many synthetic drugs undergoing metabolic activation to form reactive metabolites which are often associated with drug toxicity, it is recognized that some herbal components may also be converted to toxic, or even mutagenetic and carcinogenic metabolites by cytochrome P450s (CYPs) and less frequently by Phase II conjugating enzymes. This is exemplified by aristolochic acids (AAs) in Aristolochia spp, which undergo reduction of the nitro group by hepatic CYP1A1/2 or peroxidases in extrahepatic tissues to generate highly reactive cyclic nitrenium ions. The latter can react with macromolecules (DNA and protein), resulting in activation of H-ras oncogene and gene mutation in renal cells and finally carcinogenesis of the kidneys. Some naturally occurring flavonoids (e.g. quercetin) and alkenylbenzenes (e.g. safrole, methyleugenol and estragole) can undergo metabolic activation by sequential 1-hydroxylation and sulfation, resulting in reactive intermediates capable of forming DNA adducts and finally genotoxicity. Additional examples are pulegone present in essential oils from many mint species; and teucrin A, a diterpenoid found in germander (Teuchrium chamaedrys) used as an adjuvant to slimming dietary supplements but caused severe hepatotoxicity. Extensive pulegone metabolism generated p-cresol that was a glutathione depletory, whereas the furan ring of the diterpenoids in germander was oxidized by CYP3A4 to reactive epoxide which can inactivate hepatic CYP3A and epoxide hydrolase through covalent binding. The hepatotoxic and carcinogenic species of plant pyrrolizidine alkaloids (e.g. echimidine and jacobine), namely pyrrole-type metabolites, are generated by hepatic CYP2B6 and CYP3A4. Potential mechanisms underlying the hepatotoxicity of kava have been related to intracellular glutathione depletion and/or quinone formation. Some herbal constituents (e.g. capsaicin from chili peppers, glabridin from licorice root, oleuropein in olive oil, dially sulfone in garlic, and resveratrol found in red wine) behave as mechanism-based inhibitors of various CYPs. This may provide an explanation for some reported herb-drug interactions. In addition, the inhibition of CYPs by herbal constituents may decrease the formation of toxic metabolites and thus inhibit carcinogenesis, as CYPs play an important role in procarcinogen activation. Due to the wide use and easy availability of herbal medicines, further research should be conducted to ensure the safety and quality of herbal medicine.

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Section: Introductionmentioning

confidence: 99%

Metabolic Activation of Herbal and Dietary Constituents and Its Clinical and Toxicological Implications: An Update

Zhou¹,

Xue²,

Yu³

et al. 2007

CDM

114

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“…Although this first published effort describes the rationale of the PSTC’s Nephrotoxicity Working Group for identifying new renal safety biomarkers, the consortium also has working groups focused on hepatotoxicity, vascular injury and myotoxicity as well as genetic signatures for carcinogenicity. Much of what we discuss in the context of traditional small molecules also applies to nephrotoxicity arising from the use of alternative and complementary therapies, including herbs, natural products and nutritional supplements, especially when they are combined with conventional drugs2.…”

mentioning

confidence: 99%

Next-generation biomarkers for detecting kidney toxicity

et al. 2010

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There is a paucity of biomarkers that reliably detect nephrotoxicity. The Predictive Safety Testing Consortium (PSTC) faced several challenges in identifying novel safety biomarkers in the renal setting.The kidney is a major site of organ damage caused by drug toxicity. This frequently manifests during drug development and/or in standard clinical care. Nephrotoxicity resulting from drug exposure has been estimated to contribute to 19-25% of all cases of acute kidney injury (AKI, the currently preferred term for the clinical disorder formerly called acute renal failure) in critically ill patients 1 . Given the societal cost of nephrotoxicity and the insensitivity of current methods to detect it, sensitive methods for prediction of toxicity in preclinical studies and identification of injury in humans are extremely important for patient safety in clinical practice and in all stages of the drug-development process. It is in the interest of patients, physicians, the drug industry and health regulatory bodies to prevent new nephrotoxic drugs from entering the market or, when the medical need dictates use of such an agent, to be able to identify early and best manage nephrotoxicity.This article discusses the purview of the first effort of the PSTC-a collaboration of the biotech and pharmaceutical industry, the US Food and Drug Administration (FDA; Rockville, MD), the European Medicines Agency (EMEA; London, UK) and academia-to facilitate the qualification of renal biomarkers for safety in drug development. It brings together expertise from a variety of disciplines to organize and/or create evidentiary datasets to present to the regulatory agencies for qualification decision-making. Although this first

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Radiological Cases of the Month

Cited by 2 publications

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Metabolic Activation of Herbal and Dietary Constituents and Its Clinical and Toxicological Implications: An Update

Metabolic Activation of Herbal and Dietary Constituents and Its Clinical and Toxicological Implications: An Update

Next-generation biomarkers for detecting kidney toxicity

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