Impact of combined alpha-lipoic acid and mitoquinone supplementation on myocardial infarction in aged rats: Heart performance and molecular mechanisms.

BACKGROUND: This study aimed to investigate the effects of combined alpha-lipoic acid (ALA) and mitoquinone (Mito Q) supplementation on cardiac function and the underlying mechanisms in aged rats with myocardial infarction (MI). METHODS: The aged rats underwent left anterior descending artery (LADA) occlusion for 30 min, followed by reperfusion for 24 h. ALA (100 mg/kg, gavage) and Mito Q (10 mg/kg, IP) were administered daily for two weeks before ischemia. Cardiac function, inflammatory, and apoptotic markers were evaluated 24 h after ischemia. RESULTS: The results of this study indicated that the administration of the combination of ALA and Mito Q significantly improved cardiac function. This improvement was linked to a reduction in the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß (P < 0.001) and apoptotic markers (Bax, caspase-3, and Cyt-c), as well as a decrease in the percentage of TUNEL-positive cells (P < 0.001). CONCLUSION: The study revealed that combined intervention synergistically mitigated cardiac dysfunction by suppressing inflammatory and apoptotic pathways in aged rats with MI. Further research is needed to validate the potential of ALA and Mito Q as therapeutic options for elderly people at risk of heart attacks.

Cardioprotective effect of antioxidant combination therapy: A highlight on MitoQ plus alpha-lipoic acid beneficial impact on myocardial ischemia-reperfusion injury in aged rats.

Objective: (s): Considering the poor prognosis of ischemic heart disease and the diminished effectiveness of cardioprotective interventions in the elderly, it becomes necessary to investigate the interaction of aging with protection during myocardial ischemia/reperfusion injury (IRI). This study was conducted to assess the impact of mitoquinone (MitoQ) and alpha-lipoic acid (ALA) preconditioning on cardioprotection following IRI in aged rats. Methods: Fifty aged male Wistar rats (22-24 months old) were divided into five groups including Sham, IR, and treatment groups receiving ALA and/or MitoQ. Treatment groups were received 100 mg/kg/day ALA by oral gavage and/or 10 mg/kg/day MitoQ by intraperitoneal injection for 14 consecutive days. An in vivo model of myocardial IRI was established through ligation of coronary artery for 30 min and it's reopening for 24 h. The left ventricles were removed at the end of reperfusion to assess oxidative stress indicators, mitochondrial function, and expression of mitochondrial dynamic genes. Myocardial infarct size (IS), hemodynamic parameters, and serum lactate dehydrogenase (LDH) level were also measured. Results: Combination of MitoQ and ALA reduced oxidative stress, LDH level, and IS in aged hearts subjected to IRI. It also enhanced mitochondrial function and upregulated Mfn1, Mfn2, and Foxo1 and downregulated Drp1 and Fis1 gene expression. Co-administration of MitoQ and ALA partially restored IRI-induced hemodynamic changes to normal state. In all measured parameters, the effect of combined treatment was greater than monotherapies. Conclusion: The combination therapy of MitoQ and ALA demonstrated considerable therapeutic potential in protecting the aging heart against IRI by improving oxidative stress, mitochondrial function, and dynamics in aged rats.

Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury.

Ischaemic heart diseases (IHD) are among the major causes of mortality in the elderly population. Although timely reperfusion is a common treatment for IHD, it causes additional damage to the ischaemic myocardium known as ischaemia-reperfusion (IR) injury. Considering the importance of preventing reperfusion injuries, we aimed to examine the combination effect of mitochondrial transplantation (MT) and coenzyme Q10 (CoQ10 ) in myocardial IR injury of aged male rats. Seventy-two aged male Wistar rats were randomly divided into six groups: Sham, IR, CoQ10 , MT, combination therapy (MT + CoQ10 ) and vehicle. Myocardial IR injury was established by occlusion of the left anterior descending coronary artery followed by reopening. Young male Wistar rats were used as mitochondria donors. Isolated mitochondria were injected intraventricularly (500 µL of a respiration buffer containing 6 × 106 ± 5 × 105  mitochondria/mL) in MT-receiving groups at the onset of reperfusion. CoQ10  (10 mg/kg/day) was injected intraperitoneally for 2 weeks before IR induction. Twenty-four hours after reperfusion, haemodynamic parameters, myocardial infarct size (IS), lactate dehydrogenase (LDH) release and cardiac mitochondrial function (mitochondrial reactive oxygen species (ROS) generation and membrane potential) were measured. The combination of MT and CoQ10  improved haemodynamic index changes and reduced IS and LDH release (P < 0.05). It also decreased mitochondrial ROS generation and increased membrane potential (P < 0.05). CoQ10 also showed a significant cardioprotective effect. Combination therapy displayed greater cardioprotective effects than single treatments. This study revealed that MT and CoQ10 combination treatment can be considered as a promising cardioprotective strategy to reduce myocardial IR injury in ageing, in part by restoring mitochondrial function.

The metabolic, protective, and immune functions of Akkermansia muciniphila.

Numerous studies have almost proven the beneficial effects of gut microbiota in various aspects of human health, and even the gut microbiota is known as a new and forgotten organ. Akkermansia muciniphila, as a member of the gut microbiota, is considered a bacterium with probiotic properties; consequently, it has a remarkable position in microbiome research. This bacterium accounts for about 1-4 % of the total fecal microbiota population and is also considered a health marker. The accumulated evidence has shown a significant association between A. muciniphila and several disorders and diseases, such as obesity, fatty liver disease, diabetes, and even behavioral disorders. On the other hand, the beneficial effects of A. muciniphila in different studies have shown, such as protective role against pathogenic agents, antitumor properties, tight junctions' improvement, reduction of inflammation, gut permeability, and boosting adaptive immune responses. In this review, based on the available evidence and the latest research, we comprehensively evaluated the impact of A. muciniphila on host health from three points of view: metabolic, protective, and immune functions, as well as the possible mechanisms of each process.

Olea europaea L. (olive) leaf extract ameliorates learning and memory deficits in streptozotocin-induced diabetic rats.

Objective: The aim of the present study was to assess olive leaf extract (OLE) effects on learning and memory deficits in a model of diabetes induced by streptozotocin (STZ) in rats. Materials and methods: The rats were divided as: (1) control rats, (2) diabetic rats, and (3-6) diabetic rats treated by 100, 200, and 400 mg/kg of OLE or metformin. Using the passive avoidance test (PA), we investigated fear learning and memory behaviors. In cortical and hippocampus tissues, total levels of malondialdehyde (MDA) and thiol were measured along with the activity of catalase (CAT) and superoxide dismutase (SOD). Results: Learning and memory behavior impairment were significantly developed in diabetic rats as shown by the impairment of the PA task compared to the control group (p<0.001). In addition, elevated levels of MDA and reduced overall concentrations of thiol, CAT and SOD activity were obvious in diabetic rats' cortex and hippocampus tissues (p<0.01-p<0.001). Meanwhile, OLE in a dose-dependent manner, improved memory deficit and cognitive performance that was attributed to a reduction of lipid peroxidation and elevation of total thiol concentration, and CAT and SOD activity levels in the brain tissues (p<0.05-p<0.001). Conclusion: OLE could be effective in improving cognitive impairment in STZ-induced diabetes by oxidative stress depression.

Cardioprotective effects of Fenugreek (Trigonella foenum-graceum) seed extract in streptozotocin induced diabetic rats.

Introduction: Inadequate control of diabetes mellitus (DM) leads to considerable cardiovascular implications like diabetic cardiomyopathy (DCM). Cardiomyocyte apoptosis is one of the main mechanisms of DCM pathogenesis associated with hyperglycemia, oxidative stress, inflammation, hyperlipidemia and several other factors. Trigonella foenum-graecum (Fenugreek) has been long used as a traditional medicine and has many therapeutic effects, including anti-diabetic, anti-hyperlipidemia, anti-inflammatory and anti-oxidant properties. The current study aimed to investigate cardioprotective effects of fenugreek seed on diabetic rats. Methods: Diabetes was induced in forty-two male rats by injection of streptozotocin (STZ) (60 mg/ kg). Diabetic animals were treated with three different doses of fenugreek seed extract (50, 100 and 200 mg/kg) or metformin (300 mg/kg) for six weeks by gavage. Nondiabetic rats served as controls. Glucose, cholesterol, and triglycerides levels were measured in the blood samples, and oxidative stress markers as well as gene expression of ICAM1 , Bax and Bcl2 were assessed in the cardiac tissues of the experimental groups. Results: Diabetic rats exhibited increased serum glucose, cholesterol and triglycerides levels, elevated markers of oxidative stress thiobarbituric acid-reacting substances (TBARS) levels , total thiol groups (SH), catalase (CAT) and superoxide dismutase (SOD) activity, and enhanced apoptosis cell death (ratio of Bax/Bcl2). Fenugreek seed extract considerably improved metabolism abnormalities, attenuated oxidative stress and diminished apoptosis index. Conclusion: Our study suggests that fenugreek seed may protect the cardiac structure in STZ-induced diabetic rats by attenuating oxidative stress and apoptosis.

The Protective Effects of Pharmacologic Postconditioning of Hydroalcoholic Extract of Nigella sativa on Functional Activities and Oxidative Stress Injury During Ischemia-Reperfusion in Isolated Rat Heart.

Oxidative stress is known to act as the trigger of cardiac damage during ischemia-reperfusion (I/R) injury. Postconditioning (PoC) is employed to minimize the consequences of ischemia at the onset of reperfusion. Regarding the well-known antioxidant properties of Nigella sativa (Ns), the aim of this study was to investigate whether Nigella sativa postconditioning (Ns-PoC) could reduce IRI by lowering the formation of reactive oxygen species (ROS). Isolated rat hearts were perfused with the Langendorff apparatus, which were subjected to 20 min of preperfusion, 20 min of global ischemia, followed by 40 min of reperfusion. At the onset of reperfusion, based on the type of intervention group, a 10-min period of Krebs flow was developed along with the treatment, and then the reperfusion with Krebs solution was conducted for 30 min. Heart rate (HR) and left ventricular pressure (LVP) were recorded by isometric transducers connected to a data acquisition system. Thiobarbituric acid reactive substances (TBARS), 4-hydroxynonenal (4-HNE) levels, total thiol groups (-SH) levels, superoxide anion dismutase (SOD), and catalase (CAT) activities in myocardial tissues were detected to evaluate the oxidative stress damage degree. Ns-PoC significantly improved cardiodynamic parameters including left ventricular developed pressure (LVDP), rate pressure product (RPP), and the maximum up/down rate of the left ventricular pressure (± dp/dt) as well as SH groups, SOD, and CAT activities. Moreover, it decreased MDA and 4-HNE levels during early reperfusion. The results of this study showed that Ns-PoC ameliorated cardiac functions in isolated rat heart during I/R injuries by improving myocardial oxidative stress states, which may be related to the antioxidant effect of Ns.

Effects of levothyroxine on learning and memory deficits in a rat model of Alzheimer's disease: the role of BDNF and oxidative stress.

The effect of levothyroxine (L-T4) on the learning and memory impairment induced by streptozotocin (STZ) and brain tissue oxidative damage in rats was evaluated. An animal model of the Alzheimer's disease (AD) was established by intracerebroventricular injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). After that, the rats were treated for 3 weeks with L-T4 (10, 100 µg/kg) or normal saline. Passive avoidance (PA) learning and spatial memory were evaluated using shuttle box and Morris water maze (MWM), respectively. Finally, the rats were euthanized, their blood samples were collected for further thyroxine assessment and their brains were removed after decapitation in order to measure the oxidative stress parameters and brain-derived neurotrophic factor (BDNF). In the MWM, latency (s) increased in the AD rats compared with the normal control group while it decreased in the 10 µg/kg L-T4 injected AD rats compared with the AD group. In the PA, the latency for entering the dark compartment was lower in the AD group than in the normal control group and it decreased in the 10 µg/kg L-T4 injected AD rats. The low dose of L-T4 (10 µg/kg) reduced malondialdehyde concentration but increased thiols concentration, superoxide dismutase, catalase activities and BDNF level in hippocampal tissues of the AD rats. Injection of L-T4 (10 µg/kg) alleviated memory deficits and also improved factors of oxidative stress and BDNF level in the STZ-induced AD rats.