Oleic acid as a restorative agent in alleviating adrenaline induced altered morphofunctional milieu of gastric tissue and mitochondria.

The role of oleic acid as a protective antioxidant has recently been recognized. The present study is aimed to explore whether oleic acid can afford protection to rat gastric tissue when challenged with adrenaline. Sixty adult healthy male albino rats were divided into 10 groups comprising of 6 animals each. First group constituted the control. Rats of the second group were injected sub-cutaneously with adrenaline bitartrate at the dose of 0.3mg/kg body weight, every day for a period of 17 days. Rats of the third, to the sixth groups were orally fed with different doses of oleic acid (2.5, 5, 10, 20 mg/kg body weight/day) respectively. The rats of seventh to tenth groups were orally fed with doses of oleic acid as mentioned above and subsequently injected with adrenaline bitartrate at 0.3mg/kg body weight sub-cutaneously. After the treatment period, the animals were euthanized through cervical dislocation following light ether anaesthesia and gastric tissues were collected for morphological and biochemical studies. Subcutaneously administered pharmacological dose of adrenaline bitartrate caused oxidative stress inducing gastric lesion in male albino rats as evident from the altered levels of biomarkers of oxidative stress, activities of antioxidant and mitochondrial enzymes related to energy metabolism with changes in tissue morphology. Pre-treatment of rats with oleic acid dose-dependently protected against these gastric injuries induced by adrenaline indicating the potentiality of oleic acid in protecting against adrenaline induced gastric injury in male albino rats where antioxidant mechanisms appear to play a pivotal role in mediating such protection.

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.

Activation of SIRT1/PGC 1α/SIRT3 pathway by melatonin provides protection against mitochondrial dysfunction in isoproterenol induced myocardial injury.

AIMS: Preventing mitochondrial dysfunction and enhancing mitochondrial health and biogenesis is a crucial therapeutic approach to ameliorate injury following acute myocardial infarction. Although the antioxidant role of melatonin against ischemia/reperfusion injury has been reported, the exact mechanism of protection, in vivo, remains poorly understood. This study aims to identify and elaborate upon mechanism of melatonin protection of rat cardiac mitochondria against acute myocardial infarction. MAIN METHODS: Rats were pre-treated with melatonin (10 mg/kg body weight (b.w.); intraperitoneally, i.p.) before isoproterenol bitartrate (ISO) administration (25 mg/kg body weight (b.w.) subcutaneously,s.c.) and their effect on rat heart mitochondrial structure and function was studied. Biochemical changes in activity of biomarkers of oxidative stress, antioxidant enzymes as well as Krebs' cycle enzymes were analyzed. Gene expression studies and Isothermal titration calorimetric studies with pure catalase and ISO were also carried out. KEY FINDINGS: Melatonin was shown to reduce ISO induced oxidative stress, by stimulating superoxide dismutase activity and removing the inhibition of Krebs' cycle enzymes. Herein we report for the first time in rat model that melatonin activates the SIRT1-PGC-1α-SIRT3 signaling pathways after ISO administration, which ultimately induces mitochondrial biogenesis. Melatonin exhibited significant protection of mitochondrial architecture and topology along with increased calcium ion permeability and reactive oxygen species (ROS) generation induced by ISO. Isothermal calorimetric studies revealed that melatonin binds to ISO molecules and sequesters them from the reaction thereby limiting their interaction with catalase along with occupying the binding sites of catalase themselves. SIGNIFICANCE: Activation of SIRT1-PGC-1α-SIRT3 pathway by melatonin along with its biophysical properties prevents ISO induced mitochondrial injury in rat heart.

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.

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 ameliorates adrenaline induced dysfunction of rat heart mitochondria by binding with adrenaline: An isothermal titration calorimetry study.

AIMS: Our earlier studies revealed the cardio-protective effects of oleic acid, a monounsaturated fatty acid, against adrenaline induced myocardial injury. Moreover, it has been found to possess antioxidant properties. Thus, in the present study we have investigated the protective role of oleic acid on adrenaline induced mitochondrial dysfunction in vitro in rat heart mitochondria. MAIN METHODS: Isolated rat cardiac mitochondria was incubated in vitro with adrenaline-bitartrate alone and with graded doses of oleic acid. Biomarkers of oxidative stress, mitochondrial Krebs cycle enzymes and respiratory chain enzymes along with mitochondrial morphology, membrane potential as well as intactness were analyzed. Isothermal titration calorimetric studies with pure adrenaline and oleic acid was also carried out. KEY FINDINGS: Incubation with adrenaline, in vitro, showed elevated levels of lipid peroxidation and protein carbonylation of mitochondrial membrane, a reduced level of glutathione content along with an altered profile of mitochondrial enzymes, morphology, membrane potential as well as intactness. All these changes were found to be ameliorated when cardiac mitochondria were co-incubated with adrenaline and oleic acid, in vitro. SIGNIFICANCE: Our earlier studies demonstrated the antioxidant properties of oleic acid. This study suggests that oleic acid binds adrenaline with high affinity gradual saturation of the binding sites of adrenaline. This prevents the generation of ROS and finally providing consequent protection of the cardiac mitochondria and ameliorating adrenaline induced mitochondrial dysfunction. Hence, oleic acid may be considered as a potent future cardio-protective antioxidant.

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).