Prevention of γ-Radiation-Induced DNA Damage in Human Lymphocytes Using a Serine-Magnesium Sulfate Mixture

 Objectives: Ionising radiation has deleterious effects on human cells. N-acetylcysteine (NAC) and cysteine, the active metabolite of NAC, are well-known radioprotective agents. Recently, a serine-magnesium sulfate combination was proposed as an antidote for organophosphate toxicity. This study aimed to investigate the use of a serine-magnesium sulfate mixture in the prevention of γ-radiation-induced DNA damage in human lymphocytes as compared to NAC and cysteine. Methods: This study was carried out at the Iran University of Medical Sciences, Tehran, Iran, between April and September 2016. Citrated blood samples of 7 mL each were taken from 22 healthy subjects. Each sample was divided into 1 mL aliquots, with the first aliquot acting as the control while the second was exposed to 2 Gy of γ-radiation at a dose rate of 102.7 cGy/minute. The remaining aliquots were separately incubated with 600 μM concentrations each of serine, magnesium sulfate, serine-magnesium sulfate, NAC and cysteine before being exposed to 2 Gy of γ-radiation. Lymphocytes were isolated using a separation medium and methyl-thiazole-tetrazolium and comet assays were used to evaluate cell viability and DNA damage, respectively. Results: The serine-magnesium sulfate mixture significantly increased lymphocyte viability and reduced DNA damage in comparison to serine, magnesium sulfate, NAC or cysteine alone (P <0.01 each). Conclusion: The findings of the present study support the use of a serine-magnesium sulfate mixture as a new, non-toxic, potent and efficient radioprotective agent

Benefits of Zataria multiflora Boiss in Experimental Model of Mouse Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic condition of the intestine with unknown etiology involving multiple immune, genetic and environmental factors. We were interested to examine the effect of total extract from Zataria multiflora Boiss, a folk medicinal plant on prevention and treatment of experimental IBD. Z. multiflora was administered (400, 600, 900 p.p.m.) through drinking water to IBD mice induced by intrarectal administration of acetic acid. Prednisolone was used as the standard drug for comparison. Biochemical, macroscopic and microscopic examinations of colon were performed. Biochemical evaluation of inflamed colon was done using assay of myeloperoxidase (MPO) activity and thiobarbituric acid reactive substances (TBARS) concentration as indicators of free radical activity and cell lipid peroxidation. The activity of MPO and lipid peroxidation products (TBARS) increased in acetic acid-treated groups while recovered by pretreatment of animals with Z. multiflora (400–900 p.p.m.) and prednisolone. Z. multiflora (600 and 900 p.p.m.) and prednisolone-treated groups showed significantly lower score values of macroscopic and microscopic characters when compared with the acetic acid-treated group. The beneficial effect of Z. multiflora (900 p.p.m.) was comparable with that of prednisolone. The antioxidant, antimicrobial and anti-inflammatory potentials of Z. multiflora might be the mechanisms by which this herbal extract protects animals against experimentally induced IBD. Proper clinical investigation should be carried out to confirm the activity in human

Possible role of Mg2+ ion in the reaction of organophosphate (dichlorvos) with serine

AbstractOrganophosphate pesticides (OPs) inhibit both true and pseudo-cholinesterases by reaction with the hydroxyl group of serine in their active sites. Poisoning with OPs is commonly seen in clinics. A common antidote for OP poisoning is atropine but, after ageing and OP dealkylation, even oximes could not be effective. It has been shown that oximes are not always useful in management of OP poisoning. On the other hand, magnesium has been found effective in both clinical and experimental studies. Studies to find more effective antidotes for OP poisoning are in progress. Presently, the possible role of magnesium ion in catalysis of reaction of dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP), a water-soluble OP, with serine is proposed. The hydroxyl group of serine could be a target to which DDVP can react. Nucleophilic attack of pralidoxime to DDVP was previously investigated. To confirm the idea, data were derived from recent and previous research on the role of magnesium in phosphoryl group transfer reactions. Possible reactions of serine and pralidoxime with DDVP in the absence and the presence of magnesium ion were separately investigated theoretically.We propose that the chemical reaction of serine with DDVP exclusively occurs in the presence of a magnesium divalent cation, whereas the reaction of pralidoxime with DDVP occurs independent of the presence of the magnesium ion. The role of the dissociation constant (pKa) of functional groups in these reactions seems important.It is suggested that application of serine in combination with the magnesium cation can become a more efficient antidote for treatment of OP poisoning

Comparative verification study of silica gel-coated TLC and HPTLC plates’ performances in separation of opium alkaloids on the basis of their physicochemical properties

Abstract Background Thin layer chromatography (TLC) has been a conventional analytical method which is currently used for separation and detection of drugs in biological and non-biological samples. High-performance thin layer chromatography (HPTLC) has been claimed to have several advantages over TLC due to its smaller adsorbent particle size. Opium is the dried latex obtained from the opium poppy containing several alkaloids. Its precise and accurate detection in biological and non-biological samples is a matter of great importance in forensic and clinical toxicology. Methods In the present work, quality of commercial silica gel-coated TLC and HPTLC plates from the two best-known international manufacturers (Merck and Macherey Nagel) in separation of opium alkaloids were investigated and compared in the fluorescence quenching mode to propose the best plate for separation and identification of opium alkaloids. Particle size, zeta potential, specific surface, density, and scanning electron photomicrographs of silica gels, development time for 10 cm migration distance, number of theoretical plates (N), and resolution (R) were compared between all plates. Results Merck TLC plate showed the best separation of opium alkaloids. Although spherical-particle silica-coated Merck HPTLC plate showed narrower particle size distribution, it did not show better separation than Merck TLC plates. Conclusions On the basis of performance and price of TLC and HPTLC plates and great importance of precise and accurate detection of opium in forensic and clinical toxicology, the present work proposes conventional verified analytical TLC plates (for example Merck-TLC plate) for detection of opium alkaloids in biological and non-biological samples

The C60-Fullerene Porphyrin Adducts for Prevention of the Doxorubicin-Induced Acute Cardiotoxicity in Rat Myocardial Cells

This is a fullerene-based low toxic nanocationite designed for targeted delivery of the paramagnetic stable isotope of magnesium to the doxorubicin (DXR)-induced damaged heart muscle providing a prominent effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 hrs after a single injection (0.03 - 0.1 LD50). Magnesium magnetic isotope effect selectively stimulates the ATP formation in the oxygen-depleted cells due to a creatine kinase (CK) and mitochondrial respiratory chain-focusing "attack" of 25Mg2+ released by nanoparticles. These "smart nanoparticles" with membranotropic properties release the overactivating cations only in response to the intracellular acidosis. The resulting positive changes in the energy metabolism of heart cell may help to prevent local myocardial hypoxic (ischemic) disorders and, hence, to protect the heart muscle from a serious damage in a vast variety of the hypoxia-induced clinical situations including DXR side effects