Low dose antibiotic ingestion potentiates systemic and microbiome changes induced by silver nanoparticles.

Changes in the mammalian gut microbiome are linked to the impairment of immunological function and numerous other pathologies. Antimicrobial silver nanoparticles (AgNPs) are incorporated into numerous consumer products (e.g., clothing, cosmetics, food packaging), which may directly impact the gut microbiome through ingestion. The human health impact of chronic AgNP ingestion is still uncertain, but evidence from exposure to other antimicrobials provides a strong rationale to assess AgNP effects on organ function, immunity, metabolism, and gut-associated microbiota. To investigate this, mice were gavaged daily for 5 weeks with saline, AgNPs, antibiotics (ciprofloxacin and metronidazole), or AgNPs combined with antibiotics. Animals were weighed daily, assessed for glucose tolerance, organ function, tissue and blood cytokine and leukocyte levels. At the end of the study, we used 16S rDNA amplicon and whole-metagenome shotgun sequencing to assess changes in the gut microbiome. In mice exposed to both AgNPs and antibiotics, silver was found in the stomach, and small and large intestines, but negligible amounts were present in other organs examined. Mice exposed to AgNPs alone showed minimal tissue silver levels. Antibiotics, but not AgNPs, altered glucose metabolism. Mice given AgNPs and antibiotics together demonstrated slower weight gain, reduced peripheral lymphocytes, and elevated splenic, but not circulatory markers of inflammation. 16S rDNA profiling of cecum and feces and metagenomic sequencing of fecal DNA demonstrated that combined AgNP-antibiotic treatment also significantly altered the structure and function of the gut microbiota, including depletion of the indicator species Akkermansia muciniphila. This study provides evidence for possible biological effects from repeated ingestion of AgNP-containing consumer products when antibiotics are also being used and raises concern that an impaired gut microbiome (e.g., through antibiotic use) can potentiate the harm from chemical exposures such as AgNPs.

Effects of 5-chloro-2-methyl-4-isothiazolin-3-one and other candidate biodiesel biocides on rat alveolar macrophages and NR8383 cells.

Biocides are added to biodiesels to inhibit and remove microbial growth. The effects of 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT), a candidate biodiesel biocide, were studied using freshly isolated rat alveolar macrophages (AM) and NR8383 cell line. CMIT markedly inhibited phagocytic oxidative burst as measured by zymosan-induced chemiluminescence, and cellular cytokine secretion as measured by zymosan-induced TNF-α secretion. The 50% inhibition concentration (LC(50)) for CMIT was 0.002-0.004 mM for both cellular functions. AM exposed to CMIT for as little as 2 min showed markedly inhibited functions that persisted for at least 5 h. Sodium metabisulfite was able to partially neutralize the inhibitory activity of CMIT. Cysteine and glutathione, when present at a molar ratio of 2-1 or higher against CMIT, were effective neutralizers, while serine, histidine, alanine, and albumin were without effect. When the AM testing system was used to compare the toxicity of CMIT against three other candidate biodiesel biocides, methylene dithiocyanate (MDC) was found to be of comparable toxicity to CMIT, 2-methyl-4-isothiazolin-3-one (MIT) was much less toxic, and dimethyl acetylenedicarboxylate (DMAD) was non-toxic. Because AM is among the first cell-type exposed to inhaled biodiesel aerosols, the result suggested that CMIT present in biodiesel may produce respiratory effects, and further investigations including animal studies are warranted.

Short-term oral toxicity of three biodiesels and an ultra-low sulfur diesel in male rats.

Male rats were administered one of three biodiesels - soy oil methyl ester (SoME-2), canola oil methyl ester (CaME-2), and methyl ester of animal frying oil (FrAME-1) at 5, 50 and 500 mg/kg, or ultra-low sulphur diesel (ULSD) at 500 mg/kg. Control was administered the vehicle (corn oil) only. After 4-week treatment, serum methanol and formic acid were unchanged or minimally elevated in all treatment groups. Mild histopathological changes in the liver were observed in animals receiving 500 mg/kg biodiesels and ULSD but hepatomegaly, increased phase I and II drug-metabolizing enzyme activities and urinary ascorbic acid were found only in the ULSD group. The ULSD group had increased kidney weight, changes in kidney histopathology, and increased urinary albumin and N-acetylgluocosaminidase activity. Biodiesels and ULSD caused increase in hepatic acyl-CoA oxidase activity. ULSD and FrAME-1 caused decrease in serum free fatty acid while CaME-2 caused decreases in both serum triglycerides and free fatty acids. FrAME-1 produced an increase in liver protein carbonyls and ULSD caused increased liver glutathione. The results indicated that ULSD caused more histopathological and biochemical effects than biodiesels. Biodiesels produced lipid effects and oxidative stress that were feedstock-dependent. The mechanisms and significance of increased hepatic acyl-CoA oxidase activity required further study.