Melatonin modulates acute cardiac muscle damage induced by carbon tetrachloride — involvement of oxidative damage, glutathione, and arginine and nitric oxide metabolism

Abstract

The present study was designed to evaluate the cardioprotective effects of melatonin (a single dose of 50 mg/kg), a naturally occurring polypharmacological molecule, in Wistar rats acutely exposed to carbon tetrachloride (CCl4). This was done for the first time by tracking different biochemical parameters that reflect rat heart antioxidative/oxidative capacities, nitric oxide/arginine metabolism, and glutathione cycle. Additionally, the extrinsic apoptosis pathway-related parameters were studied. Acute exposure to CCl4 led to an increase in the studied tissue oxidant parameters (hydrogen peroxide, malondialdehyde, carbonylated protein content), as well as the activity alteration of antioxidant (catalase, superoxide dismutase and peroxidase) and glutathione metabolizing (glutathione peroxidase, S-transferase and reductase) enzymes. Furthermore, CCl4 caused a disturbance in the tissue myeloperoxidase, nitric oxide, citrulline, arginase, and inducible nitric oxide synthase content/activities and two apoptosis-related parameters, caspase-3 and FAS ligand. Melatonin as a posttreatment prevented the changes induced by CCl4 to a differing extent and, in some cases, it was so potent that it completely abolished any tissue disturbances. This study is a promising starting point for further research directed to the development of melatonin treatment in cardiac tissue-associated diseases.

Identification of novel biomarkers involved in doxorubicin-induced acute and chronic cardiotoxicity, respectively, by integrated bioinformatics

“…We and others have demonstrated that cAMP or cGMP, as the important elements of GPCRs, were widely involved in the regulation of cardiac function: both β 1 AR- and β 2 AR-mediated augmentation in cAMP led to the activation of PKA, resulting in positive inotropic and relaxant effects ( 62 , 63 ). In line with our results, Can Ciric Zdravkovic et al ( 29 ) found that DOX inhibited the cAMP/PKA/SIRT1 pathway, which could be attenuated by a Meteorin-like protein. In fact, we have discovered that Gs biased β 2 AR agonist can reduce DOX-induced chronic cardiotoxicity (data not shown here).…”

“…In line with our results, Tan et al ( 26 ) and Ni et al ( 27 ) highlighted several metabolites as potential biomarkers for DOX-induced acute cardiotoxicity. In fact, metabolic disturbances, such as heme metabolism ( 28 ), carbon metabolism ( 29 ), and oxidative phosphorylation were closely linked to oxidative stress and ROS, which acted as key factors of HF ( 30 ). This was also confirmed by our GSEA analysis.…”

Melatonin disturbed rumen microflora structure and metabolic pathways in vitro

“…The results of this study are similar to a previous report ( 66 ). Recent studies have found that the addition of MLT can enhance the cardioprotective effects of mice exposed to carbon tetrachloride and change the activity of glutathione metabolic (glutathione peroxidase, S-transferase, and reductase) enzymes ( 67 ). Liu et al ( 68 ) showed that the addition of MLT can alleviate the oxidative stress of IMD-treated cucumber and increase the activity of glutathione-S-transferase by regulating the ascorbic acid glutathione cycle.…”

D-limonene (5 (one-methyl-four-[1-methylethenyl]) cyclohexane) diminishes CCl4-induced cardiac toxicity by alleviating oxidative stress, inflammatory and cardiac markers

“…It had been further centrifuged for 30 min at 12,000 g . The supernatant was collected for LPO, inflammatory, cardiac, and in vivo antioxidant marker estimation [ 38 ].…”