Melatonin ameliorates myocardial infarction in obese diabetic individuals: The possible involvement of macrophage apoptotic factors.

In recent days, the hike in obesity-mediated epidemics across the globe and the prevalence of obesity-induced cardiovascular disease has become one of the chief grounds for morbidity and mortality. This epidemic-driven detrimental events in the cardiac tissues start with the altered distribution and metabolism pattern of high-density lipoprotein and low-density lipoprotein (LDL) leading to cholesterol (oxidized LDL) deposition on the arterial wall and atherosclerotic plaque generation, followed by vascular spasms and infarction. Subsequently, obesity-triggered metabolic malfunctions induce free radical generation which may further trigger pro-inflammatory signaling and nuclear factor kappa-light-chain-enhancer of activated B cells transcriptional factor, thus inducing interferon-gamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase. This terrifying cardiomyopathy can be further aggravated in type 2 diabetes mellitus, thereby making obese diabetic patients prone toward the development of myocardial infarction (MI) or stroke in comparison to their nondiabetic counterparts. The accelerated oxidative stress and pro-inflammatory response induced cardiomyocyte hypertrophy, followed by apoptosis in obese diabetic individuals, causing progression of athero-thrombotic vascular disease. Being an efficient antioxidative and anti-inflammatory indolamine, melatonin effectively inhibits lipid peroxidation, pro-inflammatory reactions, thereby resolving free radical-induced myocardial damages along with maintaining antioxidant reservoir to preserve cardiovascular integrity. Prolonged melatonin treatment maintains balanced body weight and serum total cholesterol concentration by inhibiting cholesterol synthesis and promoting cholesterol catabolism. Additionally, melatonin promotes macrophage polarization toward the anti-inflammatory state, providing a proper shield during the recovery period. Therefore, the protective role of melatonin in maintaining the lipid metabolism homeostasis and blocking the atherosclerotic plaque rupture could be targeted as the possible therapeutic strategy for the management of obesity-induced acute MI. This review aimed at orchestrating the efficacy of melatonin in ameliorating irrevocable oxidative cardiovascular damage induced by the obesity-diabetes correlation.

Insights into the antioxidative mechanisms of melatonin in ameliorating chromium-induced oxidative stress-mediated hepatic and renal tissue injuries in male Wistar rats.

Chromium (Cr), a hazardous heavy metal, is toxic to human health and the environment. Severe detrimental effects of Cr on different physiological systems involve oxidative stress. In the current study, sodium dichromate di-hydrate was subcutaneously injected to male Wistar rats at a dose of 5 mg/kg b.w. and experimented up to 14 days to induce alterations in hepatic and renal tissues. Another group of rats was pre-treated with melatonin at three different doses (5, 10, and 20 mg/kg b.w.; orally) and 20 mg/kg b.w. dose was evidenced to provide maximal protection against Cr-induced alterations. The study demonstrated that melatonin efficiently preserved body weight, organ weight, intracellular antioxidant enzymes, and tissue morphology. Furthermore, melatonin was also found to protect organ damage markers, oxidative stress-biomarkers, activities of pro-oxidant enzymes, levels of reactive oxygen species (ROS), nitric oxide (NO), and collagen content through its antioxidative mechanisms. Moreover, melatonin effectively decreased tissue Cr content through its metal-chelating activity. Hence, the present study has established melatonin as a promising antioxidant for conserving the liver and kidney tissues from Cr-induced oxidative damage thereby strengthening the notion that this small indoleamine can act as a future therapeutic against Cr-induced oxidative stress-mediated tissue damage.

Oleic acid prevents erythrocyte death by preserving haemoglobin and erythrocyte membrane proteins.

Haemolysis of erythrocytes upon exposure to haemato-toxic phenylhydrazine (PHZ), makes it an experimental model of anaemia and a partial model of ß-thalassaemia, where oxidative stress (OS) was identified as principal causative factor. Oleic acid (OA) was evidenced to ameliorate such stress with antioxidative potential. Erythrocytes were incubated in vitro using 1 mM PHZ, 0.06 nM OA. Erythrocyte membrane protein densities and haemoglobin (Hb) status were examined. Any interaction of Hb with PHZ/OA was checked by calorimetric and spectroscopic analysis using pure molecules. Occurrence of erythrocyte apoptosis and involvement of free iron in all groups were evaluated. PHZ exposure to erythrocytes results in OS with subsequent apoptosis as evidenced from increased lipid peroxidation and translocation of phosphatidylserine in outer membrane. Preservations of erythrocyte cytoskeletal architecture and membrane bound enzyme activity were found in presence of OA. Moreover, both heme and globin of Hb was examined to be conserved by OA. Presence of OA, impeded apoptosis also, possibly by thwarting Hb breakdown followed by free iron release and consequent free radical generation. Additionally, direct sequential binding of OA with PHZ endorsed another protective mechanism of OA toward erythrocytes. OA affords protection to erythrocytes by conserving its major components and prevents haemolysis which project OA as a haemato-protective agent. Apart from combating PHZ toxicity, anti-apoptotic action of OA strongly suggests its usage in anaemia and ß-thalassaemia patients to curb irreversible erythrocyte breakdown. This research strongly recommends OA in pure form or from dietary sources as a therapeutic against haemolytic disorders.

Insights into the ameliorative effect of oleic acid in rejuvenating phenylhydrazine induced oxidative stress mediated morpho-functionally dismantled erythrocytes.

Phenylhydrazine (PHZ), an intermediate in the synthesis of fine chemicals is toxic for human health and environment. Despite of having severe detrimental effects on different physiological systems, exposure of erythrocytes to PHZ cause destruction of haemoglobin and membrane proteins leading to iron release and complete haemolysis of red blood cells (RBC). Involvement of oxidative stress behind such action triggers the urge for searching a potent antioxidant. The benefits of consuming olive oil is attributed to its 75% oleic acid (OA) content in average. Olive oil is the basic component of Mediterranean diet. Hence, OA has been chosen in our present in vitro study to explore its efficacy against PHZ (1 mM) induced alterations in erythrocytes. Four different concentrations of OA (0.01 nM, 0.02 nM, 0.04 nM and 0.06 nM) were primarily experimented with, among which 0.06 nM OA has shown to give maximal protection. This study demonstrates the capability of OA in preserving the morphology, intracellular antioxidant status and the activities of metabolic enzymes of RBCs that have been diminished by PHZ, through its antioxidant mechanisms. The results of the present study firmly establish OA as a promising antioxidant for conserving the health of erythrocyte from PHZ toxicity which indicate toward future possible use of OA either singly or in combination with other dietary components for protection of erythrocytes against PHZ induced toxic cellular changes.

Attenuation of arsenic induced high fat diet exacerbated oxidative stress mediated hepatic and cardiac injuries in male Wistar rats by piperine involved antioxidative mechanisms.

The current study explored the efficacy of piperine in attenuating arsenic induced high fat diet aggravated oxidative stress mediated injury in hepatic and cardiac tissues of male Wistar rats. Oral administration of piperine significantly (p < 0.05) reduced the levels of organ specific and oxidative stress biomarkers in arsenic and high fat diet treated rat hepatic and cardiac tissues in a dose dependant manner with the dose of 60 mg/kg b.w. exhibiting maximum protection. Arsenic induced high fat diet aggravated oxidative stress mediated damages in liver and heart tissues led to decreased activities of antioxidant enzymes, ROS generation, diminished activities of Krebs' cycle and respiratory chain enzymes, collapsed mitochondrial membrane potential, mitochondrial DNA damage along with altered lipid metabolism and inflammatory cytokine levels. Histochemical and histopathological studies supported the above findings. Piperine efficiently counteracted the arsenic induced high fat diet aggravated oxidative stress mediated damages by modulating antioxidant defense mechanism along with free radical quenching ability. These findings indicate that piperine protected the arsenic induced high fat diet aggravated hepatic and cardiac injuries which underline the importance of piperine in providing a possible therapeutic regime for the amelioration of arsenic-induced high fat diet aggravated oxidative stress mediated organ damages.