Study of CO⋯HN Hydrogen bond interactions in amyloid beta (Aβ): A DFT study of the electric field gradient and CS tensors and NBO analysis

A systematic computational density functional theory (DFT) study was carried out in amyloid-beta (Aβ) structure to investigate the hydrogen bonding interactions (HBs) effects on Chemical shielding (CS) and electric field gradient (EFG) tensors in site of hydrogen, oxygen, nitrogen and carbon nuclei. The results indicate that these tensors are more sensitive to the HB interactions in dimer model than those of trimer model. The calculated 15N and 13C in CS tensors in trimer model are in good agreement with experimental data. Natural bonding orbital analysis, NBO, indicate a reasonable correlation between 14N quadrupole coupling constant (C_Q) and strength of Fock matrix elements (F_ij). Moreover, the quantum chemical calculations indicated that the intermolecular the HB interactions play an essential role in variation of the relative orientation of CS and EFG tensors of nitrogen, hydrogen and oxygen nuclei in the molecular frame axes. Finally, 17O C_Q and η_Q show great dependency to backbone conformation, specifically dihedral angles ψ (psi).     

Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca²⁺ on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca²⁺ pools (EGTA or BAPTA-AM) and NO (l-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca²⁺ entrance was induced by A23187 in HepG2. Cell death, Ca²⁺ mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca²⁺ concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and l-NAME enhanced, GCDCA-induced cell death. The reduction of Ca²⁺ entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca²⁺ entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca²⁺ concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca²⁺-dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.     

The neuroprotective effects of intraperitoneal injection of hydrogen in rabbits with cardiac arrest

Objective

The purpose of this study was to investigate the neuroprotective effects of intraperitoneal injection of hydrogen (H₂) in rabbits with cardiac arrest (CA).

Methods

A rabbit model of CA was established by the delivery of alternating current between the esophagus and chest wall to induce ventricular fibrillation. Before CA, the animals were randomly divided into four groups: a sham group (no CA), a CA group, a CA + low dose (10 ml/kg) H₂ group (CA + H₂ group 1), and a CA + high dose (20 ml/kg) H₂ group (CA + H₂ group 2). In the first experiment, animals were observed for 72 h after the restoration of spontaneous circulation (ROSC). The neurological scores were assessed at 24, 48 and 72 h after ROSC. The rabbits that survived until 72 h were sacrificed using an overdose of anesthetic, and the brain tissues were collected and Nissl-stained to observe nerve cell damage in the hippocampal CA1 area. In addition, TUNEL assay was performed to detect apoptosis. In the second experiment, animals were observed for 6 h after ROSC. Blood samples and brain hippocampal tissues were collected, and differences in oxidative stress indicators were compared among the four groups.

Results

Intraperitoneal injection of H₂ improved the 72-h survival rate and neurological scores, reduced neuronal injury and inhibited neuronal apoptosis. Intraperitoneal injection of H₂ reduced oxidative stress indicators in the plasma and hippocampal tissues and enhanced antioxidant enzyme activity. No significant difference was observed between the two CA groups treated with different doses of H₂.

Conclusions

Intraperitoneal injection of H₂ is a novel hydrogen administration method and can reduce cerebral ischemia-reperfusion injury and improve the prognosis of cardiopulmonary cerebral resuscitation in a rabbit model of CA.     

Microtubule-associated protein tau in development, degeneration and protection of neurons

As a principal neuronal microtubule-associated protein, tau has been recognized to play major roles in promoting microtubule assembly and stabilizing the microtubules and to maintain the normal morphology of the neurons. Recent studies suggest that tau, upon alternative mRNA splicing and multiple posttranslational modifications, may participate in the regulations of intracellular signal transduction, development and viability of the neurons. Furthermore, tau gene mutations, aberrant mRNA splicing and abnormal posttranslational modifications, such as hyperphosphorylation, have also been found in a number of neurodegenerative disorders, collectively known as tauopathies. Therefore, changes in expression of the tau gene, alternative splicing of its mRNA and its posttranslational modification can modulate the normal architecture and functions of neurons as well as in a situation of tauopathies, such as Alzheimer's disease. The primary aim of this review is to summarize the latest developments and perspectives in our understanding about the roles of tau, especially hyperphosphorylation, in the development, degeneration and protection of neurons.     

Medicinal properties of mangosteen (Garcinia mangostana)

Many tropical plants have interesting biological activities with potential therapeutic applications. Garcinia mangostana Linn. (GML) belongs to the family of Guttiferae and is named “the queen of fruits”. It is cultivated in the tropical rainforest of some Southeast Asian nations like Indonesia, Malaysia, Sri Lanka, Philippines, and Thailand. People in these countries have used the pericarp (peel, rind, hull or ripe) of GML as a traditional medicine for the treatment of abdominal pain, diarrhea, dysentery, infected wound, suppuration, and chronic ulcer.     

D-arginine action against neurotoxicity induced by glucocorticoids in the brain

Glucocorticoids (GC) are necessary for normal life but elevated levels of GC have been implicated in the development of several neurological diseases and psychiatric disorders. Nowadays, it is well known that high levels of GC in the central nervous system (CNS) generate an increase in the production of reactive oxygen species (ROS), derived mainly from the nitric oxide (NO) pathway. Accordingly, there is an increase of l-arginine (l-Arg.) availability. This report reviews the evidence that d-arginine (d-Arg.) induces normalization of l-Arg. resulting in protection against GC neurotoxic actions in the hippocampus. It is important to highlight that this D-amino acid does not interfere with the expected peripheral effects of GC such as suppression of the hypothalamic-pituitary-adrenal axis (HPA axis) and the immune response, commonly used in clinical practice.     

Inhalation of hydrogen gas attenuates cisplatin-induced ototoxicity via reducing oxidative stress

Objective

Cisplatin, an anticancer drug used extensively to treat a broad range of tumors, has strong ototoxic side effects induced by reactive oxygen species (ROS). Recently, it has been reported that hydrogen gas (H₂) is a new antioxidant by selectively reducing hydroxyl radical, the most cytotoxic ROS. The present study was designed to investigate whether H₂ treatment is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress.

Methods

The animals were intraperitoneally given a 30 min infusion of 16 mg/kg cisplatin or the same volume of saline. H₂ treatment was given twice with 2% H₂ inhalation for 60 min starting at 1 h and 6 h after cisplatin or saline injection, respectively. The hearing status of all animals was evaluated by auditory brainstem responses (ABR). The hair cell damage was observed by phalloidin staining. In addition, the levels of oxidative products in serum and cochlear tissue were measured.

Results

We found that H₂ treatment significantly attenuated cisplatin-induced hearing loss evaluated by click-evoked and tone burst ABR threshold. Furthermore, histological analysis revealed that 2% H₂ treatment significantly alleviated cisplatin-induced hair cell damage in the organ of corti. In addition, cisplatin significantly increased the levels of malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in serum and cochlear tissue, which was attenuated by H₂ treatment.

Conclusion

These results demonstrate that H₂ is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress. Therefore, H₂ has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the cisplatin ototoxicity.     

Oxidative stress and potential biomarkers in tomato seedlings subjected to soil lead contamination

Oxidative stress and defense response in leaves of tomato seedlings exposed to extraneous lead (Pb) at 0–500 mg kg⁻¹ soil for nearly 2 months were investigated. Superoxide radical (O₂^{http://www.sciencedirect.com/scidirimg/entities/rad" alt="radical dot" title="radical dot" border="0">−}) was quantified by electron paramagnetic resonance (EPR). Results showed that levels of O₂^{http://www.sciencedirect.com/scidirimg/entities/rad" alt="radical dot" title="radical dot" border="0">−}, malondialdehyde (MDA), carbonyl group and superoxide dismutase (SOD) increased with the increase of bioavailable Pb. The O₂^{http://www.sciencedirect.com/scidirimg/entities/rad" alt="radical dot" title="radical dot" border="0">−} level was well correlated with MDA, carbonyl groups and SOD activities, suggesting that O₂^{http://www.sciencedirect.com/scidirimg/entities/rad" alt="radical dot" title="radical dot" border="0">−} might be responsible for them. Intensities in two bands of SOD isoenzymes increased along with added Pb in treatments against control, implying that multigenic expression in SOD enzymes were activated to counteract O₂^{http://www.sciencedirect.com/scidirimg/entities/rad" alt="radical dot" title="radical dot" border="0">−} stress. Heat shock protein 70 (HSP70) was induced sensitively by soil Pb, which was to alleviate oxidative damage (i.e. increased carbonyl groups). The overall results indicated that HSP70 and O₂^{http://www.sciencedirect.com/scidirimg/entities/rad" alt="radical dot" title="radical dot" border="0">−} were the most sensitive parameters and the combination of them might be potential biomarkers of soil Pb contamination in tomato seedlings.