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 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.

Beta-estradiol protects against copper-ascorbate induced oxidative damage in goat liver mitochondria in vitro by binding with ascorbic acid.

AIMS: ß-Estradiol (ß-E), one of the chemical forms of female gonad hormone exhibited antioxidant efficacy in biochemical system, in vitro. The aim of the study was to investigate whether any other mechanism of protection by ß-E to hepatic mitochondria in presence of stressor agent i.e.,a combination of Cu2+ and ascorbic acid is involved. MAIN METHODS: Freshly prepared goat liver mitochondria was incubated with stressors and 1 µM ß-E and post incubated with the same concentration at 37 °C at pH 7.4. Mitochondrial viability, biomarkers of oxidative stress, activities of Krebs cycle enzymes, mitochondrial membrane potential, Ca2+ permeability were measured. Mitochondrial morphology and binding pattern of ß-E with stressors were also studied. KEY FINDINGS: Upon incubation of mitochondria with Cu, ascorbic acid and their combination there is a significant decline in activities of four of Krebs cycle enzymes in an uncompetitive manner with a concomitant increase in Ca2+ permeability and membrane potential of inner mitochondrial membrane, which is withdrawn during co-incubation with ß-E, but was not reversed during post incubation with the ß-E. The final studies on mitochondrial membrane morphology using scanning electron microscope also exhibited damage. Isothermal titration calorimetry data also showed the negative heat change in the mixture of ß-E with ascorbic acid and also its combination with Cu2+. SIGNIFICANCE: Our results for the first time demonstrated that ß-E protects againstCu2+-ascorbate induced oxidative stress by binding with ascorbic acid. The new mechanism of binding of ß-E with stress agents may have a future therapeutic relevance.

Oleic acid protects against cadmium induced cardiac and hepatic tissue injury in male Wistar rats: A mechanistic study.

AIMS: The aim of the present study was to evaluate the possible antioxidant role of oleic acid (OA) against Cd-induced injuries in the heart and liver tissues of male Wistar rats. MAIN METHODS: Rats were treated with either vehicle (control), or OA (10 mg/kg b.w., fed orally), or Cd (0.44 mg/kg b.w., s.c.), or both (OA + Cd) for 15 days. Following completion of the treatment period, biomarkers of organ damage and oxidative stress including ROS, activities of antioxidant enzymes and their level, activities of Krebs cycle enzymes and respiratory chain enzymes were measured. Levels of interleukins (IL-1ß, IL-6, IL-10), tumor necrosis factor (TNF-α) and nuclear factor kappa B (NFκB) were estimated to evaluate the state of inflammation. In addition, changes in mitochondrial membrane potential and status of cytochrome c (Cyt c) were also studied. KEY FINDINGS: Pre-treatment of rats with OA significantly protected against Cd-induced detrimental changes possibly by decreasing endogenous ROS through regulation of antioxidant defense system, inflammatory responses and activities of metabolic enzymes. Moreover, OA was also found to restore mitochondrial membrane potential possibly by regulating Cyt c leakage thereby increasing mitochondrial viability. SIGNIFICANCE: Our results for the first time demonstrated systematically that OA provided protection against Cd-induced oxidative stress mediated injuries in rat heart and liver tissues through its antioxidant mechanism. The results raise the possibility of using OA singly or in combination with other antioxidants or diet in the treatment of situations arising due to oxidative stress and may have future therapeutic relevance.

Aqueous bark extract of Terminalia arjuna protects against cadmium-induced hepatic and cardiac injuries in male Wistar rats through antioxidative mechanisms.

Cadmium (Cd) is one of the most ubiquitous toxic heavy metal in the environment. The present study was conducted to evaluate the protective role of aqueous bark extract of Terminalia arjuna (TA) against Cd induced oxidative damage in hepatic and cardiac tissues as the TA bark extract has folkloric medicinal use in the treatment of various hepatic and cardiac disorders. Male Wistar rats were divided into 4 groups. The control group was treated with normal saline as the vehicle; the second group orally administered with TA (20 mg/kg bw) daily for 15 days; the third group injected with Cd-acetate (0.44 mg/kg bw, s.c.) every alternate day for a period of 15 days; and the fourth group was administered with TA, 60 min prior to Cd treatment. The biomarkers of organ damage were significantly increased in the Cd treated groups. Besides, a significant alteration in the tissue levels of biomarkers of oxidative stress, the activities and the levels of antioxidant enzymes was observed following treatment with Cd. Additionally, some of the enzymes were found to be inhibited uncompetitively by Cd when tested in an in vitro system. Furthermore, evidence gathered from studies on the histological parameters and mitochondrial membrane potential in both the tissues argue in favour of the possible protective role of TA against Cd induced damage. Finally, gas chromatography-mass spectrometry revealed the presence of eight major bioactive phytochemicals in aqueous bark extract of TA having potent free radical scavenging property. The results indicate that the extract could protect hepatic and cardiac tissues against Cd-induced oxidative stress mediated damages through antioxidant mechanism(s).

Protective effects of piperine against copper-ascorbate induced toxic injury to goat cardiac mitochondria in vitro.

Piperine, the main alkaloid of black pepper, Piper nigrum Linn., is an important Indian spice used in traditional food and medicine in India. In the present study, we investigated the antioxidant activities of piperine against copper-ascorbate induced toxic injury to mitochondria obtained from a goat heart, in vitro. Incubation of isolated cardiac mitochondria with copper-ascorbate resulted in elevated levels of lipid peroxidation and protein carbonylation of the mitochondrial membrane, a reduced level of mitochondrial GSH and altered status of antioxidant enzymes as well as decreased activities of pyruvate dehydrogenase and the Kreb's cycle enzymes, altered mitochondrial morphology, mitochondrial swelling, di-tyrosine level and mitochondrial DNA damage. All these changes were found to be ameliorated when the cardiac mitochondria were co-incubated with copper-ascorbate and piperine, in vitro. Piperine, in our in vitro experiments, was found to scavenge hydrogen peroxide, superoxide anion free radicals, hydroxyl radicals and DPPH radicals, in a chemically defined system, indicating that this compound may provide protection to cardiac mitochondria against copper-ascorbate induced toxic injury through its antioxidant activities. The results of this study suggest that piperine may be considered as a future therapeutic antioxidant and may be used singly or as a co-therapeutic in the treatment of diseases associated with mitochondrial oxidative stress.

Protective effect of aqueous Curry leaf (Murraya koenigii) extract against cadmium-induced oxidative stress in rat heart.

Treatment of rats with a low dose of cadmium chloride caused a significant damage in the rat cardiac tissue indicated by the increase in the level of serum glutamate oxaloacetate transaminase and lactate dehydrogenase1 activities. Histological studies confirmed the damage due to cadmium. That cadmium-induced tissue damage was caused due to oxidative stress was evident from the changes observed in the levels of lipid peroxidation and reduced glutathione, the protein carbonyl content, and the alterations in the activities of cardiac antioxidant and pro-oxidant enzymes. Treatment of rats with cadmium also caused alterations in the activities of mitochondrial Kreb's cycle as well as respiratory chain enzymes. All these changes were ameliorated when the rats were pre-treated with an aqueous extract of Curry leaf (Murraya koenigii). The studies indicated that the aqueous extract of Curry leaf protects the rat cardiac tissue against cadmium-induced oxidative stress possibly through its antioxidant activity. As curry leaf is consumed by people as part of their diet in India and South-East Asian and some European countries as well, and, as it has no reported side-effects, the results seem to have relevance at places where humans are exposed to cadmium environmentally or occupationally.

Melatonin protects against isoproterenol-induced myocardial injury in the rat: antioxidative mechanisms.

The present study was undertaken to explore the protective effect of melatonin against isoproterenol bitartrate (ISO)-induced myocardial injury in rat. Treatment of rats with ISO increased the level of lipid peroxidation products and decreased the reduced glutathione levels in cardiac tissue indicating that this synthetic catecholamine induces oxidative damage following oxidative stress. Pretreatment of ISO-injected rats with melatonin at a dose of 10 mg/kg body weight, i.p. prevented these changes. Additionally, melatonin also restored the activities and the levels of antioxidant enzymes which were found to be altered by ISO treatment. Treatment of rats with ISO resulted into an increased generation of hydroxyl radicals with melatonin pretreatment significantly reducing their production. Finally, treatment of rats with ISO caused a lowering of systolic pressure with reduced cardiac output and diastolic dysfunction whereas melatonin pretreatment significantly restored many of these parameters to normal. The findings document melatonin's ability to provide cardio protection at a low pharmacological dose. Melatonin has virtually no toxicity which raises the possibility of this indole being a therapeutic treatment for ischemic heart disease.