Rat Liver Mitochondrial Dysfunction Induced by an Organic Arsenical Compound 4-(2-Nitrobenzaliminyl) Phenyl Arsenoxide.

Arsenic is successfully used in cancer chemotherapy and several cancer treatments on account of its apoptogenic effects. However, it is environmentally hazardous with potential for toxicity when distributed in the soil, water, and food, and long exposure to water contaminated with Arsenic may induce cancers. Some research studies have reported that liver is the storage site and an important target organ for Arsenic toxicity. In the present work, a new kind of organic arsenic compound, 4-(2-nitrobenzaliminyl) phenyl arsenoxide (NPA), was synthesized, and its potential involvement of mitochondria was explored. The results presented that the toxicology of NPA, at least in part, mediated mitochondrial function and may thoroughly destroy mitochondrial membrane physiological functions. NPA induced mitochondrial permeability transition pore (mtPTP) opening that induces mitochondrial biochemical abnormalities as evidenced by mitochondrial swelling, mitochondrial membrane potential breakdown, membrane fluidity alterations, and the strikingly remarkable protection of CsA. Meanwhile, both the decreased respiration rate of state 4 and the increased inner membrane H(+) permeabilization revealed that the inner membrane function regarding important energy production chain was destroyed. The toxicity of NPA is due to its interaction with mitochondrial membrane thiol protein. This conclusion is based on the protective effects of RR, DTT, and MBM(+).

Nd(III)-induced rice mitochondrial dysfunction investigated by spectroscopic and microscopic methods.

The production capacity and yield of neodymium (Nd) in China have ranked the first in the world. Because of its unique biophysical and biochemical properties, Nd compounds have entered into the agricultural environment greatly to promote plant growth. Mitochondria play a crucial role in respiration and metabolism during the growth of plants. However, little is known about the mechanism by which Nd act at the mitochondrial level in plant cells. In this study, rice mitochondrial swelling, collapsed transmembrane potential and decreased membrane fluidity were examined to be important factors for mitochondria permeability transition pore (mPTP) opening induced by Nd(III). The protection of cyclosporin A (CsA) and dithiothreitol (DTT) could confirm that Nd(III) could trigger mPTP opening. Additionally, mitochondrial membrane breakdown observed by TEM and the release of cytochrome c (Cyt c) could also elucidate the mPTP opening from another point of view. At last, the study showed that Nd(III) could restrain the mitochondrial membrane lipid peroxide, so it might interact with anionic lipid too. This detection will be conductive to the safe application of Nd compounds in agriculture and food industry.

Resonance energy transfer, pH-induced folded states and the molecular interaction of human serum albumin and icariin.

Icariin is a flavonol glycoside with a wide range of pharmacological and biological activities. The pharmacological and biological functions of flavonoid compounds mainly originate from their binding to proteins. The mode of interaction of icariin with human serum albumin (HSA) has been characterized by fluorescence spectroscopy and far- and near-UV circular dichroism (CD) spectroscopy under different pH conditions. Fluorescence quenching studies showed that the binding affinity of icariin with HSA in the buffer solution at different pH values is: Ka (pH 4.5) > Ka (pH 3.5) > Ka (pH 9.0) > Ka (pH 7.0). Red-edge excitation shift (REES) studies revealed that pH had an obvious effect on the mobility of the tryptophan microenvironment and the addition of icariin made the REES effect more distinct. The static quenching mechanism and number of binding sites (n ≈ 1) were obtained from fluorescence data at three temperatures (298, 304 and 310 K). Both ∆H(0) < 0 and ∆Ѕ(0) < 0 suggested that hydrogen bonding and van der Waal's interaction were major driving forces in the binding mechanism, and this was also confirmed by the molecular simulation results. The distance r between the donor (HSA) and the acceptor (icariin) was calculated based on Förster non-radiation energy transfer theory. We found that pH had little impact on the energy transfer between HSA and icariin. Far- and near-UV CD spectroscopy studies further indicated the influence of pH on the complexation process and the alteration in the protein conformation upon binding.

Bioenergetic investigation of the effects of La(III) and Ca(II) on the metabolic activity of Tetrahymena thermophila BF5.

The heat flux of Tetrahymena thermophila BF5 during growth and the effects of La(3+) and Ca(2+) on them were investigated with microcalorimetry; simultaneously, morphological changes of T. thermophila were obtained by light microscope. La(3+) in low concentration (0-5.0 x 10(-4) mol/l) remarkably stimulated T. thermophila metabolism, but high dose of La(3+) (5.8-8.6 x 10(-4) mol/l) restrained it in a linear manner with IC(50) being 7.2 x 10(-4) mol/l. In contrast, low concentration of Ca(2+) did not manifest obvious stimulation on T. thermophila metabolism; moreover, the IC(50) of Ca(2+) was much higher than that of La(3+). Low concentration of La(3+) did not lead to changes in appearance of T. thermophila, but low dose of Ca(2+) clearly promoted the cell proliferation. In addition, the morphological changes of T. thermophila evoked by high concentrations of La(3+) and Ca(2+) were consistent with relevant microcalorimetric results. It is concluded that La and Ca influence T. thermophila via different pathways, and La represents toxic action rather than Ca analogy.