Serum and urine metabolomics analysis reveals the role of altered metabolites in patulin-induced nephrotoxicity.

Various studies have identified the kidney as a target organ for patulin (PAT)-induced toxicity. However, detailed mechanistic insights into PAT-induced nephrotoxicity had not yet been done. Therefore, along with classical toxicological parameters, liquid chromatography-high resolution massed spectrometry (LC-HRMS) based metabolomics has been carried out to delineate the mechanism(s) of PAT-induced nephrotoxicity.An in vivo study was conducted using male Wistar rats, divided into three groups. PAT (25 µg/kg b.wt and 100 µg/kg b.wt) and, control were given through oral gavage, 5 days/week for 28 days. At the end of the experiment, changes in the mean body/ organ weight, food and water intake, expression of marker proteins of kidney injury, and histopathological changes were investigated. Furthermore, using LC-HRMS based metabolomics was performed on the serum and urine of PAT-exposed rats. The histopathological and toxicological analysis revealed a significant increase in glomerular mesangial cells, vacuolar degeneration, and cast deposition in the proximal convoluted tubules. The metabolomics showed metabolic perturbations in amino and fatty acid-related metabolic pathways in serum and urine of PAT-treated rats. In conclusion this study expands our understanding of PAT-induced metabolic alterations and its effects on renal function.

Comparison of polycyclic aromatic hydrocarbon levels in placental tissues of Indian women with full- and preterm deliveries.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants formed from combustion products of fossil fuels, cigarette smoking and in grilled/smoked foods. They are reported to alter trophoblast proliferation in placenta, in addition to disturbing its endocrine functions, which may be able to increase the risk of preterm delivery in pregnant women. The present study was planned to assess possible involvement of PAHs exposure of pregnant women (measured as placental PAHs concentrations) with preterm delivery cases among women of Lucknow city (India). We performed a case-control study and a total of 60 mothers (n=31 full term and n=29 preterm deliveries) were recruited at a local nursing home of Lucknow, for the period of August 2005-February 2006. Subsequent to parturition, placental tissues from each participant were immediately collected and kept at -20 degrees C until PAHs analyses. Placental tissue PAHs concentrations were determined by HPLC, using a fluorescence detector. Mean+/-SD placental level (61.91+/-12.43ppb) of benzo(b)fluoranthene, a carcinogenic PAH, was found significantly elevated (p<0.05) among women with preterm delivery when compared with the level (23.84+/-7.01) in women having full-term deliveries. In the same way, non-carcinogenic fluoranthene level (325.91+/-45.14ppb) was also detected to be higher in the preterm delivery group compared to 208.6+/-21.93ppb level from the full-term delivery group of women. Additionally naphthalene, acenaphthylene, phenanthrene, anthracene, benzo(a)pyrene and dibenzo(a,h)anthracene levels in placental tissue were also found to be higher in the preterm delivery group of women but the difference did not reach statistically significant levels. This foremost study from India with modest samples size and limited statistical power does not show a substantial involvement of PAHs with preterm delivery, but higher concentrations of placental PAHs detected among preterm delivery group of women could show some possible association with these environmental toxicants. Further study with large sample size, controlled for confounders and great statistical power, is reasonable to elucidate the association of PAHs exposure with preterm delivery of women in India.