Effects of silver nanoparticles on rat hepatic cytochrome P450 enzyme activity
ABSTRACT Silver nanoparticles (AgNPs) are increasingly used in various products and consequentially the potential adverse effects associated with exposure to them are of concern. This study investigated the effects of AgNPs on the hepatic drug-metabolizing enzymes of the cytochrome P450 (CYP) families 1, 2 and 3, using both in vitro and in vivo biological assays. AgNPs were orally administered to Sprague-Dawley rats at various concentrations (0-1000 mg/kg body weight/day) for 2 weeks. No effect was found on the plasma levels of ALT, AST and ALP in all treated rat groups, and no significant change in the activities of CYP1A, CYP2C, CYP2D, CYP2E1 and CYP3A was observed for all tested AgNP doses. The results correlated with the observation that no AgNPs were detected in the liver sections of the tested rats. However, the in vitro system using rat liver microsomes demonstrated a strong inhibition of CYP2C (IC(50) = 28 µg/mL) and CYP2D (IC(50) = 23 µg/mL) activities, but not of CYP1A, CYP2E1 and CYP3A activities (IC(50) > 100 µg/mL) at concentrations up to 100 µg/mL of AgNPs. The inhibitory effect of AgNPs on these CYPs indicates the possibility of the AgNP-drug interaction when co-administered with some medicines and this may cause adverse effects to patients.
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ABSTRACT: Orally administered silver has been described to be absorbed in a range of 0.4 to 18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least a factor of five before a level of concern to the general population is reached.Regulatory Toxicology and Pharmacology 11/2013; 68(1). DOI:10.1016/j.yrtph.2013.11.002 · 2.14 Impact Factor
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ABSTRACT: Diabetes mellitus and hepatocellular carcinoma both have detrimental impact on health worldwide. Type II diabetes and liver cancer share many causative factors, but biological correlation between the two diseases still remains elusive. The study was aimed to evaluate the effect of induction of diabetes during the development of hepatocarcinogenesis in rats. Rats were divided into four groups namely, normal control, diabetic control, carcinogen control and carcinogen treated rats treated with streptozotocin (to make them diabetic). Hepatocarcinogenesis was initiated in rats by diethylnitrosamine (200 mg kg −1 body weight, single i.p. injection on day 0 only). Then 2-acetylaminoflourene (0.5% w/w) was given daily in diet for 18 weeks to promote the carcinogenesis. On the 16th week, streptozotocin (65 mg kg −1 body weight, single i.p. injection) was administered to initiate diabetes in rats. On the 20th week, animals were sacrificed and various biochemical changes and histopathological alterations in liver were investigated. Carcinogen treated rats made diabetic had significantly lower cytochrome P-450 content as compared to diabetic control rats and had slightly elevated cytochrome P-450 level as compared to that of carcinogen control rats. Marked enhancements of UDP-glucuronosyl transferase, glutathione S-transferase activities and lipid peroxidation levels were observed in carcinogen treated rats made diabetic as compared to those activities and levels in diabetic control and carcinogen control rats. Histopathological investigation of hepatic tissue has favoured the rapid progress of development of hepatocellular carcinoma in carcinogen treated rats made diabetic. In conclusion, induction of diabetes during the development of hepatocellular carcinogenesis inevitably promotes the progression of the later disease.
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ABSTRACT: Nanomaterials (NMs) are engineered for commercial purposes such as semiconductors, building materials, cosmetics, and drug carriers, while natural nanoparticles (NPs) already exist in the environment. Due to their unique physicochemical properties, they may interact actively with biological systems. Some of these interactions might be detrimental to human health, and therefore studies on the potential 'nanotoxicity' of these materials in different organ systems are warranted. The purpose of developing the concept of nanotoxicity is to recognize and evaluate the hazards and risks of NMs and evaluate safety. This review will summarize and discuss recent reports derived from cell lines or animal models concerning the effects of NMs on, and their application in, the endocrine system of mammalian and other species. It will present an update on current studies of the effects of some typical NMs-such as metal-based NMs, carbon-based NMs, and dendrimers-on endocrine functions, in which some effects are adverse or unwanted and others are favorable or intended. Disruption of endocrine function is associated with adverse health outcomes including reproductive failure, metabolic syndrome, and some types of cancer. Further investigations are therefore required to obtain a thorough understanding of any potential risk of pathological endocrine disruption from products containing NMs. This review aims to provide impetus for further studies on the interactions of NMs with endocrine functions.Small 05/2013; 9(9-10). DOI:10.1002/smll.201201517 · 7.51 Impact Factor