Electrophysiological and molecular mechanisms of protection by iron sucrose against phosphine-induced cardiotoxicity: A time course study

The present study was designed for determining the exact mechanism of cytotoxic action of aluminum phosphide (AlP) in the presence of iron sucrose as the proposed antidote. Rats received AlP (12 mg/kg) and iron sucrose (5-30 mg/kg) in various sets and were connected to cardiovascular monitoring device. After identification of optimum doses of AlP and iron sucrose, rats taken in 18 groups received AlP (6 mg/kg) and iron sucrose (10 mg/kg), treated at six different time points, and then their hearts were surgically removed and used for evaluating a series of mitochondrial parameters, including cell lipid peroxidation, antioxidant power, mitochondrial complex activity, ADP/ATP ratio and process of apoptosis. ECG changes of AlP poisoning, including QRS, QT, P-R, ST, BP and HR were ameliorated by iron sucrose (10 mg/kg) treatment. AlP initiated its toxicity in the heart mitochondria through reducing mitochondrial complexes (II, IV and V), which was followed by increasing lipid peroxidation and the ADP/ATP ratio and declining mitochondrial membrane integrity that ultimately resulted in cell death. AlP in acute exposure (6 mg/kg) resulted in an increase in hydroxyl radicals and lipid peroxidation in a time-dependent fashion, suggesting an interaction of delivering electrons of phosphine with mitochondrial respiratory chain and oxidative stress. Iron sucrose, as an electron receiver, can compete with mitochondrial respiratory chain complexes and divert electrons to another pathway. The present findings supported the idea that iron sucrose could normalize the activity of mitochondrial electron transfer chain and cellular ATP level as vital factors for cell escaping from AlP poisoning. © 2015 Informa Healthcare USA, Inc. All rights reserved

Molecular and biochemical evidence on the protection of cardiomyocytes from phosphine-induced oxidative stress, mitochondrial dysfunction and apoptosis by acetyl-l-carnitine

The aim of the present study was to investigate the efficacy of acetyl-l-carnitine (ALCAR) on pathologic changes of mitochondrial respiratory chain activity, ATP production, oxidative stress, and cellular apoptosis/necrosis induced by aluminum phosphide (AlP) poisoning. The study groups included: the Sham that received almond oil only; the AlP that received oral LD50 dose of aluminum; the AC-100, AC-200, and AC-300 which received concurrent oral LD50 dose of AlP and single 100, 200, and 300mg/kg of ALCAR by intraperitoneal injection. After 24h, the rats were sacrificed; the heart and blood sample were taken for measurement of biochemical and mitochondrial factors. The results specified that ALCAR significantly attenuated the oxidative stress (elevated ROS and plasma iron levels) caused by AlP poisoning. ALCAR also increased the activity of cytochrome oxidase, which in turn amplified ATP production. Furthermore, flow cytometric assays and caspase activity indicated that ALCAR prohibited AlP-induced apoptosis in cardiomyocytes. © 2015 Elsevier B.V.

Lithium decreases streptozocin-induced diabetic neuropathy in rats by inhibiting of adenosine triphosphate (ATP) degradation

One of the most frequent complications of diabetes is diabetic peripheral neuropathy. Hyperglycemia would result in the advancement of this condition over a period of time. The most effective way in preventing diabetic neuropathy is regular control of glucose. In this study; we evaluated the effects of lithium onstreptozocin (STZ)-induced diabetic neuropathy in rats. Diabetic neuropathy was created 7 weeks after administration of STZ (45 mg/kg). Lithium was added to drinking water (450 mg/l) for 7 weeks and its plasma level after this period of time was 0.17±0.02 mmol/l. Levels of adenosine triphosphate (ATP) in dorsal root ganglion (DRG) neurons, oxidative stress parameters, open-field activity test and morphological analysis were assessed in this investigation. Currentresults showed significant elevation of oxidative stress biomarkers, reduction of ATP, abnormal morphology of DRG neurons and decrease of total distance moved in rats with STZ-induced diabetic neuropathy. The alterations in mentioned parameters were considerably restored by lithium treatment. These findings provide evidence for protective effects of lithium on STZ-induced diabetic neuropathy. © 2018 Tehran University of Medical Sciences. All rights reserved

Lithium decreases streptozocin-induced diabetic neuropathy in rats by inhibiting of adenosine triphosphate (ATP) degradation

One of the most frequent complications of diabetes is diabetic peripheral neuropathy. Hyperglycemia would result in the advancement of this condition over a period of time. The most effective way in preventing diabetic neuropathy is regular control of glucose. In this study; we evaluated the effects of lithium onstreptozocin (STZ)-induced diabetic neuropathy in rats. Diabetic neuropathy was created 7 weeks after administration of STZ (45 mg/kg). Lithium was added to drinking water (450 mg/l) for 7 weeks and its plasma level after this period of time was 0.17±0.02 mmol/l. Levels of adenosine triphosphate (ATP) in dorsal root ganglion (DRG) neurons, oxidative stress parameters, open-field activity test and morphological analysis were assessed in this investigation. Currentresults showed significant elevation of oxidative stress biomarkers, reduction of ATP, abnormal morphology of DRG neurons and decrease of total distance moved in rats with STZ-induced diabetic neuropathy. The alterations in mentioned parameters were considerably restored by lithium treatment. These findings provide evidence for protective effects of lithium on STZ-induced diabetic neuropathy. © 2018 Tehran University of Medical Sciences. All rights reserved

Usporedba djelovanja blokatora kalcijevih kanala, blokatora autonomnoga živčanog sustava te inhibitora slobodnih radikala na hiposekreciju inzulin iz izolirnih langerhansovih otočića štakora uzrokovanu diazinonom

Hyperglycaemia has been observed with exposure to organophosphate insecticides. This study was designed to compare the effects of calcium channel blockers, alpha-adrenergic, beta-adrenergic, and muscarinic receptor blockers, and of free radical scavengers on insulin secretion from diazinon-treated islets of Langerhans isolated from the pancreas of rats using standard collagenase digestion, separation by centrifugation, and hand-picking technique. The islets were then cultured in an incubator at 37 °C and 5 % CO2. In each experimental set 1 mL of 8 mmol L-1 glucose plus 125 µg mL-1 or 625 µg mL-1 of diazinon were added, except for the control group, which received 8 mmol L-1 glucose alone. The cultures were then treated with one of the following: 30 µmol L-1 atropine, 100 µmol L-1 ACh + 10 µmol L-1 neostigmine, 0.1 µmol L-1 propranolol, 2 µmol L-1 nifedipine, 50 µmol L-1 phenoxybenzamine, or 10 µmol L-1 alphatocopherol. In all experiments, diazinon significantly reduced glucose-stimulated insulin secretion at both doses, showing no dose dependency, as the average inhibition for the lower dose was 62.20 % and for the higher dose 64.38 %. Acetylcholine and alpha-tocopherol restored, whereas atropine potentiated diazinoninduced hyposecretion of insulin. Alpha-, beta- and calcium channel blockers did not change diazinoninduced effects. These findings suggest that diazinon affects insulin secretion mainly by disturbing the balance between free radicals and antioxidants in the islets of Langerhans and by inducing toxic stress.U osoba izloženih organofosfatnim insekticidima zamijećen je nastanak hiperglikemije. Svrha je ovo istraživanja bila usporediti djelovanje blokatora kalcijevih kanala, alfa i beta-adrenergičkih i muskarinskih receptora te inhibicije slobodnih radikala na lučenje inzulina iz Langerhansovih otočića izoliranih iz štakora tretiranih diazinonom. Otočići su izolirani iz gušterače štakora s pomoću standardnog postupka digestije kolagenazom, odvajanja centrifugiranjem i metodom ručnog probira (engl. hand-picking) te su kultivirani u inkubatoru pri 37 °C i 5 % CO2. Pokusne su kulture inkubirane s 1 mL glukoze u koncentraciji od 8 mmol L-1 te diazinonom u dozi od 125 μg mL-1, odnosno 625 μg mL-1. U kontrolu je dodana samo glukoza u koncentraciji od 8 mmol L-1. Nakon toga je u kulture dodan jedan od sljedećih agenasa: 30 µmol L-1 atropin, 100 µmol L-1 ACh + 10 µmol L-1 neostigmin, 0,1 µmol L-1 propranolol, 2 µmol L-1 nifedipin, 50 µmol L-1 fenoksibenzamin, odnosno 10 µmol L-1 alfa-tokoferol. U svim je pokusima diazinon značajno smanjio lučenje inzulina, s time da je doza od 125 μg mL-1 dovela do 62,2 %-tne inhibicije, a doza od 625 μg mL-1 do 64,38 %-tne inhibicije lučenja inzulina, što upućuje na djelovanje neovisno o dozi. Acetilkolin i alfa-tokoferol su ponovno potaknuli lučenje inzulina, za razliku od atropina koji ga je dodatno smanjio. Primjena blokatora alfa i beta-adrenergičkih receptora te blokatora kalcijevih kanala nije utjecala na djelovanje diazinona. Autori zaključuju da diazinon utječe na lučenje inzulina ponajviše narušavanjem ravnoteže između slobodnih radikala i antioksidansa u Langerhansovim otočićima te dovodi do toksičnoga stresa

Evaluation of anti-melanogenic activity of Ziziphus jujuba fruits obtained by two different extraction methods

Background and objectives: Dried pulps and peels of Ziziphus jujuba fruits are commonly applied as food because of their high nutritional value. It has been widely used in traditional medicine as laxative, tonic, wound healing agent and appetizer. The aim of this study was to evaluate the anti-melanogenic effects of Z. jujuba fruit. Methods: Fruit extracts were obtained by two different extraction methods, percolation (cold extraction) and soxhlet (hot extraction) using methanol 80% as the solvent. The total phenolic and flavonoid contents, DPPH radical scavenging activity and anti-tyrosinase capacity of the MeOH extracts from Z. jujuba fruits were evaluated in vitro. In addition, the effects of fruit extracts on the melanin content and cytotoxicity on human melanoma SKMEL-3 cells were determined after 72 hours. Results: The amount of total phenolic and flavonoid contents of the cold extract were found higher in comparison to the hot extract. Moreover, the antioxidant (SC50 =1.40 mg/mL) and anti-tyrosinase activities (IC50 = 0.54 mg/mL) of the cold extract were significantly stronger than the hot extract. At the dose of 500 μg/mL, the cold extract showed weaker toxicity to the melanoma cells than the hot extract. Melanin content of the cold extract was reduced to 30% at this concentration, while the hot extract had no inhibitory effect on melanin formation. Conclusion: The results showed that the percolation method was more suitable for extraction of the (poly) phenolics from Z. jujuba fruits. In addition, the results of tyrosinase activity and melanin content assays suggested that the cold extract of Z. jujuba fruit can be considered as a dermatological whitening agent in skin care products

Evaluation of anti-melanogenic activity of Ziziphus jujuba fruits obtained by two different extraction methods

Abstract Background and objectives: Dried pulps and peels of Ziziphus jujuba fruits are commonly applied as food because of their high nutritional value. It has been widely used in traditional medicine as laxative, tonic, wound healing agent and appetizer. The aim of this study was to evaluate the antimelanogenic effects of Z. jujuba fruit. Methods: Fruit extracts were obtained by two different extraction methods, percolation (cold extraction) and soxhlet (hot extraction) using methanol 80% as the solvent. The total phenolic and flavonoid contents, DPPH radical scavenging activity and antityrosinase capacity of the MeOH extracts from Z. jujuba fruits were evaluated in vitro. In addition, the effects of fruit extracts on the melanin content and cytotoxicity on human melanoma SKMEL-3 cells were determined after 72 hours. Results: The amount of total phenolic and flavonoid contents of the cold extract were found higher in comparison to the hot extract. Moreover, the antioxidant (SC 50 =1.40 mg/mL) and anti-tyrosinase activities (IC 50 = 0.54 mg/mL) of the cold extract were significantly stronger than the hot extract. At the dose of 500 μg/mL, the cold extract showed weaker toxicity to the melanoma cells than the hot extract. Melanin content of the cold extract was reduced to 30% at this concentration, while the hot extract had no inhibitory effect on melanin formation. Conclusion: The results showed that the percolation method was more suitable for extraction of the (poly) phenolics from Z. jujuba fruits. In addition, the results of tyrosinase activity and melanin content assays suggested that the cold extract of Z. jujuba fruit can be considered as a dermatological whitening agent in skin care products