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Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO2-Induced Aging in Male Rats.

ABSTRACT: Arsenic (As) poisoning is widespread due to exposure to pollution. The toxic level of (As) causes oxidative stress-induced aging and tissue damage. Since melatonin (MLT) has anti-oxidant and anti-aging properties, we aimed to evaluate the protective effect of MLT against the toxicity of sodium arsenite (NaAsO2). Healthy male NMRI mice were divided into eight different groups. The control group received a standard regular diet. Other groups were treated with varying diets, including MLT alone, NaAsO2, and NaAsO2 plus MLT. After one month of treatment, biochemical and pathological tests were performed on blood, heart, and lung tissue samples. NaAsO2 increased the levels of TNF-α, 8-hydroxy-2-deoxy guanosine (8OHdG), malondialdehyde (MDA), reactive oxygen species (ROS), and high mobility group box 1 (HMGB1), increased the expression of TNF receptor type 1-associated death domain (TRADD) mRNA and telomerase reverse transcriptase, and decreased the expression of Klotho (KL) mRNA in both plasma and tissues. In contrast, MLT reduced MDA, ROS, HMGB1, lactate, and TNF-α enhanced the mRNA expression of KL, and suppressed the mRNA expression of the TERT and TRADD genes. Thus, MLT confers potent protection against NaAsO2- induced tissue injury and oxidative stress.

SUBMITTER: Baeeri M

PROVIDER: S-EPMC8587717 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO<sub>2</sub>-Induced Aging in Male Rats.

Baeeri Maryam M Didari Tina T Khalid Madiha M Mohammadi-Nejad Solmaz S Daghighi Seyed Mojtaba SM Farhadi Ramtin R Rahimifard Mahban M Bayrami Zahra Z Haghi-Aminjan Hamed H Foroumadi Roham R Gholami Mahdi M Abdollahi Mohammad M

Molecules (Basel, Switzerland) 20211031 21

Arsenic (As) poisoning is widespread due to exposure to pollution. The toxic level of (As) causes oxidative stress-induced aging and tissue damage. Since melatonin (MLT) has anti-oxidant and anti-aging properties, we aimed to evaluate the protective effect of MLT against the toxicity of sodium arsenite (NaAsO<sub>2</sub>). Healthy male NMRI mice were divided into eight different groups. The control group received a standard regular diet. Other groups were treated with varying diets, including ML ...[more]

PMID: 34771016

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Project description:IntroductionPodophyllotoxin (PPT) is a high-content and high-activity compound extracted from the traditional Chinese medicinal plant Dysosma versipellis (DV) which exhibits various biological activities. However, its severe toxicity limits its use. In clinical settings, patients with DV poisoning often experience adverse reactions when taking large doses in a short period. The heart is an important toxic target organ, so it is necessary to conduct 24-h acute cardiac toxicity studies on PPT to understand its underlying toxicity mechanism.MethodsBased on the concept of the toxicological evidence chain (TEC), we utilized targeted metabolomic and transcriptomic analyses to reveal the mechanism of the acute cardiotoxicity of PPT. The manifestation of toxicity in Sprague-Dawley rats, including changes in weight and behavior, served as Injury Phenotype Evidence (IPE). To determine Adverse Outcomes Evidence (AOE), the hearts of the rats were evaluated through histopathological examination and by measuring myocardial enzyme and cardiac injury markers levels. Additionally, transcriptome analysis, metabolome analysis, myocardial enzymes, and cardiac injury markers were integrated to obtain Toxic Event Evidence (TEE) using correlation analysis.ResultsThe experiment showed significant epistaxis, hypokinesia, and hunched posture in PPT group rats within 24 h after exposure to 120 mg/kg PPT. It is found that PPT induced cardiac injury in rats within 24 h, as evidenced by increased serum myocardial enzyme levels, elevated concentrations of cardiac injury biomarkers, and altered cardiac cell morphology, all indicating some degree of cardiac toxicity. Transcriptome analysis revealed that primary altered metabolic pathway was arachidonic acid metabolism after PPT exposure. Cyp2e1, Aldob were positively correlated with differential metabolites, while DHA showed positive correlation with differential genes Fmo2 and Timd2, as well as with heart injury markers BNP and Mb.ConclusionThis study comprehensively evaluated cardiac toxicity of PPT and initially revealed the mechanism of PPT-induced acute cardiotoxicity, which involved oxidative stress, apoptosis, inflammatory response, and energy metabolism disorder.

Project description:The aim of the present was to ameliorate the protective effect of exogenous melatonin and insulin against the diabetes induced alterations in the different hematological variables. Albino rats were administrated streptozotocin at the dose of 15 mg/kg for 6 days. Total 54 rats were randomly selected for the experimental purpose and were divided into two major groups. Group-1 consisting twenty four (24) and were further sub-divided into four (4) different groups viz. group-I served as normal control, group-II served as melatonin treated, group-III served as insulin treated and group-IV served as glibenclamide treated. Group-2 consisting thirty (30) rats were given streptozotocin (STZ) injection (15 mg/kg) for 6 days. After confirmation of diabetes by measuring blood glucose level, animals having blood glucose level above 250 mg/dl) confirmed as diabetic. Thirty (30) Diabetic rats were further subdivided into following sub-groups and were given different therapeutic treatments, Viz group-I served as Diabetic control, group-II treated with melatonin, group-III treated with insulin, group-IV given treatment of melatonin and insulin and group-V were given treatment of glibenclamide respectively. Diabetic rats showed modulation in all the studied hematological variables. Diabetic rats displayed significant decline in RBCs count, HB level and its associated indices (HCT, RDW, MCV, MCH, MCHC), WBCs and its related indices (polymorphs and lymphocytes) and platelet distribution width (PDW %) whereas platelet count showed significant increase. Nonetheless alone as well as combined treatment of exogenous melatonin and insulin restored all altered hematological parameters. However, significant recovery was found in the group in which combined dose of melatonin and insulin was administrated. Therefore, it might be concluded that combined administration of melatonin and insulin will be better remedy to normalize the altered blood profile during the diabetic condition.

Dataset Information

Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO2-Induced Aging in Male Rats.

Publications

Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO<sub>2</sub>-Induced Aging in Male Rats.

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