Reproductive and metabolic toxic effects of polystyrene microplastics in adult female Wistar rats: a mechanistic study.

Microplastics, such as polystyrene microplastics (PS-MPs), have become an emerging environmental hazard for animals and humans. Long-term exposure to PS-MPs has led to neurotoxicity, reproductive dysfunction, and carcinogenesis. The goal of this study was to evaluate the effect of sub-chronic exposure of PS-MPs on metabolic and reproductive functions in female rats. The PS-MPs were prepared by cryogenic technique. The PS-MPs were given orally to female Wistar rats for 45 days at 2.5, 5, and 10 mg/kg/day. The average PS-MPs' size diameter was 876 nm. The PS-MPs administration resulted in a significant decrease in the activity of superoxide dismutase and catalase in the liver and ovary. The effect of PS-MPs on reduced glutathione and lipid peroxidation in the liver and ovarian tissues of rats was statistically insignificant. The PS-MP exposure exhibited an increase in the levels of triglycerides, total cholesterol, and low-density lipoprotein and decrease in high-density lipoprotein. The PS-MPs caused glucose intolerance and increase in insulin. Moreover, the PS-MP exposure increased follicle stimulating hormone, estradiol, and testosterone. Serum level of interleukin-6 and nuclear factor kappa B (NF-κB) was elevated in animals treated with PS-MPs. The PS-MP exposed rats showed normal ovarian histology, but activated hepatic stellate cells and liver fibrosis. It is concluded that the sub-chronic exposure to PS-MPs resulted in metabolic and endocrine disruption in female rats through oxidative damage, hormonal imbalance, and chronic inflammation.

Antihypertensive Activity in High Salt-Induced Hypertensive Rats and LC-MS/MS-Based Phytochemical Profiling of Melia azedarach L. (Meliaceae) Leaves.

Melia azedarach L. leaves have been traditionally used but not scientifically evaluated for antihypertensive activity. The focus of the present work was to carry out the detailed phytochemical profiling and antihypertensive potential of methanolic extract and subsequent fractions of this plant. The tandem mass spectrometry-based phytochemical profiling of M. azedarach extract (Ma.Cr) and fractions was determined in negative ionization mode while molecular networking was executed using the Global Natural Product Social (GNPS) molecular networking platform. This study resulted in the identification of 29 compounds including flavonoid O-glycosides, simple flavonoids, triterpenoidal saponins, and cardenolides as the major constituents. Ma.Cr at the concentration of 300 mg/kg resulted in a fall in blood pressure (BP), i.e., 81.44 ± 2.1 mmHg in high salt-induced hypertensive rats in vivo, in comparison to normotensive group, i.e., 65.36 ± 1.8 mmHg at the same dose. A decrease in blood pressure was observed in anaesthetized normotensive and hypertensive rats treated with extract and various fractions of M. azedarach. A reasonable activity was observed for all fractions except the aqueous fraction. The highest efficacy was shown by the ethyl acetate fraction, i.e., 77.06 ± 3.77 mmHg in normotensive and 88.96 ± 1.3 mmHg in hypertensive anaesthetized rats. Ma.Cr and fractions showed comparatively better efficacy towards hypertensive rats as compared to rats with normal blood pressure. Blood pressure-lowering effects did not change upon prior incubation with atropine. In vitro testing of Ma.Cr and polarity-based fractions resulted in L-NAME sensitive, endothelium-dependent vasodilator effects on aortic tissues. Pretreatment of aorta preparations with Ma.Cr and its fractions also blocked K+-induced precontractions indicating Ca2+ channel blocking activity comparable to verapamil. The extract and polarity-based fractions did not reveal a vasoconstrictor response in spontaneously beating isolated rat aorta. Ma.Cr and fractions when used in atrial preparations resulted in negative inotropic and chronotropic effects. These effects in atrial preparations did not change in the presence of atropine. These effects of extract and fractions explained the antihypertensive potential of M. azedarach and thus provided a scientific basis for its ethnopharmacological use in the treatment of hypertension. Among the constituents observed, flavonoids and flavonoid O-glycosides were previously reported for antihypertensive potential.

Formation of polybrominated dibenzofurans (PBDFs) and polybrominated diphenyl ethers (PBDEs) from oxidation of brominated flame retardants (BFRs).

Brominated aromatic rings constitute main structural entities in virtually all commercially deployed brominated flame retardants (BFRs). Oxidative decomposition of BFRs liberates appreciable quantities of bromobenzenes (BBzs). This contribution reports experimental measurements for the generation of notorious polybrominated dibenzofurans (PBDFs) and polybrominated diphenyl ethers (PBDEs) from oxidation of monobromobenzene (MBBz). In the light of developed product profiles, we map out reaction pathways and report kinetic parameters for PBDFs and PBDEs formation from coupling reactions of MBBz molecule and its derived ortho-bromophenoxy (o-BPhxy) radical using quantum chemical calculations. The identification and quantitation of product species involve the use of gas chromatograph - triple quadrupole mass spectrometer (GC-QQQMS) operating in the multiple reaction monitoring (MRM) mode. Bimolecular reactions of MBBz and o-BPhxy result in the generation of twelve pre-PBDF intermediates, of which four can also serve as building blocks for the synthesis of PBDEs. These four intermediates are denoted as pre-PBDE/pre-PBDF, with the remaining eight symbolised as pre-PBDF. The resonance-stabilised structure of the o-BPhxy radical accumulates more spin density character on its phenoxy O atom (30.9 %) in reference to ortho-C and para-C sites. Thus, the formation of the pre-PBDE/pre-PBDF structures via O/o-C couplings advances faster as it requires lower activation enthalpies (79.2 - 84.9 kJ mol-1) than the pre-PBDF moieties, which arise via pairing reactions involving o-C(H or Br)/o-C(H or Br) sites (97.2 - 180.2 kJ mol-1). Kinetic analysis indicates that, the O/o-C pre-PBDE/pre-PBDF adducts self-eject the out-of-plane H atoms to produce PBDEs, rather than undergo a three-step mechanism forming PBDFs. However, experimental measurements demonstrate PBDEs appearing in lower yields as compared to those of PBDFs; presumably due to H- and Br-induced conversion of the PBDEs into PBDFs following a simple ring-closure reaction. High reaction temperatures facilitate loss of ortho Br atom from PBDEs, followed by cyclisation step to generate PBDFs. PBDFs are observed in a narrow temperature range of 700-850 °C, whereas PBDEs form between 550-850 °C. Since formation mechanisms of PBDFs and polybrominated dibenzo-p-dioxins (PBDDs) are typically only sensitive to the bromination at ortho positions, the results reported herein apply also to higher brominated isomers of BBzs.

Photodecomposition properties of brominated flame retardants (BFRs).

This study investigates the geometric and electronic properties of selected BFRs in their ground (S0) and first singlet excited (S1) states deploying methods of the density functional theory (DFT) and the time-dependent density functional theory (TDDFT). We estimate the effect of the S0→ S1 transition on the elongations of the C-Br bond, identify the frontier molecular orbitals involved in the excitation process and compute partial atomic charges for the most photoreactive bromine atoms. The bromine atom attached to an ortho position in HBB (with regard to C-C bond; 2,2',4,4',6,6'-hexabromobiphenyl), TBBA (with respect to the hydroxyl group; 2,2',6,6'-tetrabromobisphenol A), HBDE and BTBPE (in reference to C-O linkage; 2,2',4,4',6,6'-hexabromodiphenylether and 1,2-bis(2,4,6-tribromophenoxy)ethane, respectively) bears the highest positive atomic charge. This suggests that, these positions undergo reductive debromination reactions to produce lower brominated molecules. Debromination reactions ensue primarily in the aromatic compounds substituted with the highest number of bromine atoms owing to the largest stretching of the C-Br bond in the first excited state. The analysis of the frontier molecular orbitals indicates that, excitations of BFRs proceed via π→π*, or π→σ* or n→σ* electronic transitions. The orbital analysis reveals that, the HOMO-LUMO energy gap (EH-L) for all investigated bromine-substituted aromatic molecules falls lower (1.85-4.91 eV) than for their non-brominated analogues (3.39-8.07 eV), in both aqueous and gaseous media. The excitation energies correlate with the EH-L values. The excitation energies and EH-L values display a linear negative correlation with the number of bromine atoms attached to the molecule. Spectral analysis of the gaseous-phase systems reveals that, the highly brominated aromatics endure lower excitation energies and exhibit red shifts of their absorption bands in comparison to their lower brominated congeners. We attained a satisfactory agreement between the experimentally measured absorption peak (λmax) and the theoretically predicted oscillator strength (λmax) for the UV-Vis spectra. This study further confirms that, halogenated aromatics only absorb light in the UV spectral region and that effective photodegradation of these pollutants requires the presence of photocatalysts.

Photodecomposition of bromophenols.

Photodecomposition of bromophenols (BPs) represents a potent channel of debromination and elimination of these species in the environment. From this perspective, the present contribution reports geometrical parameters, electronic absorption spectra and excited states of the complete series of BPs in their ground state (S0), as well as their first singlet exited state (S1). We calculate excitation energies for S0 → S1 transition within the framework of the time-dependent density functional theory (TDDFT). We estimate and discuss charges on bromine atoms and HOMO-LUMO energy gaps (E(H-L)) as molecular descriptors for the photoreactivity of BPs and photo-induced debromination mechanism of BPs. Spectral patterns reveal that, as the degree of bromination increases, peaks of absorption spectra red-shift toward wavelengths near 300 nm, for the pentabrominated phenol. Based on the analysis of optimised geometries and Hirshfeld's atomic charges, photodebromination of BPs commences via the loss of an ortho Br atom. The excitation energies decrease linearly with increasing number of bromine atoms. This indicates that, higher brominated congeners of BPs photodecompose more readily than lower brominated congeners.

Formation of mixed halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs).

This contribution investigates mechanistic and kinetic parameters pertinent to formation of mixed dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) from the condensation reactions involving 2-chlorophenoxy (2-CPxy) and 2-bromophenoxy (2-BPxy) radicals. Keto-ether structures act as direct intermediates for the formation of DD, 1-MCDD, 1-MBDD, 1-B,6-CDD and 1-B,9-CDD molecules. Likewise, diketo adducts initiate the formation of 4-MCDF, 4-MBDF and 4-B,6-CDF compounds through interconversion and rearrangement reactions. As formation mechanisms of halogenated dibenzo-p-dioxins and dibenzofurans from precursors of brominated and chlorinated phenols are insensitive to substitution at meta and para sites, our mechanistic and kinetic analysis of reactions involving 2-BPxy and 2-CPxy should also apply to higher halogenated phenoxy radicals.