The Role Of Pi3k/akt Pathway In Myocardial Contractility
PI3K can influence myocardial contractile strength due to increased expression of multiple Ca2+-regulating proteins . In the PTEN/PI3K signaling pathway, PTEN results in a dramatic decrease in cardiac contractility, while PI3K exhibits an increase in cardiac contractility. Loss of PI3K is associated with substantial increases in contractility and relaxation, and thus PI3K acts as a negative regulation of cardiac contractility, and it can modulate contractility in the absence of exogenous agonist . In addition, Akt regulates the contractile function in cardiomyocytes and increases inotropism through the functional regulation of Ca+-handling proteins .
Chronic Kidney Disease Causes And Risk Factors
There are several causes and risk factors for chronic kidney disease, including:
- Certain autoimmune conditions
The Centers for Disease Control and Prevention estimates that approximately half of individuals with severely reduced kidney function who are not receiving dialysis are unaware they have CKD. Specific urine and blood tests that assess kidney damage and filtration rate are used to identify CKD.
CKD has been associated with certain health complications, such as anemia, depression, stroke, increased risk of infections, and imbalanced mineral levels in the blood. Individuals with CKD are also at an increased risk of premature mortality associated with cardiovascular disease and cancer, making it critical to address CKD as early as possible.
Effect Of La Supplementation On Ferroptosis In Fa
Iron-dependent lipid perioxidation could cause cell necrosis in tubular epithelium . We further explored FA-induced tubular cell death using TUNEL staining. As depicted in Figure 7, we found that there were more TUNEL-positive tubular cells in the FA group, and the number of TUNEL-positive tubular cells in the low-dose and high-dose LA treatment groups was significantly reduced, while there was no particular preference for the higher-dose group. This indicated that LA could reduce ferroptosis-mediated tubular cell death without significant dose dependence.
Figure 7. Lipoic acid supplementation decreases ferroptosis-mediated tubular cells death caused by FA injection. Mice are treated as described in Figure 1. Representative images by TUNEL staining, showing the ferroptosis-mediated tubular cell death. White arrowheads for TUNEL-positive tubular cells on kidney tissue sections nuclei are labeled with DAPI . Bar=50m. The number of TUNEL-positive nuclei per high-power field . For the FA group vs. the control group, *indicates p< 0.05, and **indicates p< 0.01. For the LA-treated groups vs. the FA group, #indicates p< 0.05, and ##indicates p< 0.01.
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The Use Of Alpha Lipoic Acid In Kidney Disease
So, what does this all mean for people with kidney disease?
Well, as you can see, alpha lipoic acid provides benefits for people regardless of the cause of their kidney damage and can help to prevent and treat some of the typical consequences of kidney disease.
Alpha lipoic acid also protects the kidneys against acute kidney injury by eliminating free radicals, improving glomerular function, reducing renal inflammation and improving blood flow to the kidneys. It has also been shown to offer protection from chemotherapy induced kidney damage.
La Supplementation Ameliorated Histopathologic Damage And Renal Dysfunction In Fa
To determine whether LA supplementation could protect against FA-induced renal damage, histological analysis was evaluated with H& E and PAS staining. As observed in H& E staining, FA injection induced severe tubular damage, indicated by detachment of tubular cells, dilation of tubules, swelling of tubular cells, degeneration of epithelial cells, and interstitial inflammatory cells infiltration. In line with this tubular damage, the kidney in the FA group also showed aggravated pathological damage by PAS staining, characterized by necrotic tubular epithelial cells, tubular cast, and ablation of brush. While these tubular damage were alleviated by LA supplementation. Moreover, tubular injuries were assessed by quantification of HE-stained sections and revealed significantly increased tubulointerstitial injury scores in mice injected with FA injection, which were reduced by LA supplementation in a dose-dependent manner, but without statistical significance. In addition, renal function was measured to investigate the protective effect of LA on FA-induced AKI. Consistently, the FA injection induced dramatic increases in serum creatinine and BUN levels, indicating impaired renal function, while these functional parameters associated with AKI were reduced by LA supplementation, indicating the amelioration of renal function. The results above are summarized in Figure 1.
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Tocopherols And Alpha Lipoic Acid Treatment Chronic Kidney Disease
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|First Posted : March 30, 2006Last Update Posted : July 9, 2009|
Supplementing With Alpha Lipoic Acid
As I mentioned earlier, the body does produce small amounts of alpha lipoic acid and we also get some through our diet however there are certain circumstances where the body cant keep up with the amount of alpha lipoic acid it needs and kidney disease is one of them.
Luckily, alpha lipoic acid is available as a supplement and is one of the key nutrients we recommend for the treatment of kidney disease.
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What Is Alpha Lipoic Acid
Alpha lipoic acid is a very unique vitamin like antioxidant. Its the only antioxidant that is fat soluble and water soluble which has led to it being referred to as a universal antioxidant.
Being both fat and water soluble allows it to travel to all parts of the body and because of these unique properties, it is able to enter certain parts of the cell that most other antioxidants arent able to reach as well as crossing the blood brain barrier.
Our bodies can make a small amount of alpha lipoic acid, but the amount produced isnt enough to fulfill our bodies requirements, so we get most of it from our diet. Food sources of alpha lipoic acid include spinach, broccoli, potatoes, yeast, tomatoes, brussels sprouts, red meat and organ meat.
The Kidney Disease Solution Cookbook
The 133-page guidebook is packed full of recipes that are easy to follow and need to add to create an appropriate kidney-friendly diet. Each recipe is designed to meet the necessary daily nutritional needs of your body. It also shows you how to adopt healthy eating habits. Whats more, it also provides special recipes for other health conditions you might suffer from, like hypertension and diabetes.
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So What Does This Mean
We recommend using the R form of alpha lipoic acid as it is the natural and most active form of alpha lipoic acid and is also better absorbed by the body than the S form. The R-lipoic acid is generally more expensive than the synthetic form or the blend but with that you get a better-quality supplement with a greater therapeutic value.
Alpha Lipoic Acid: Safety Benefits And How To Use
Alpha-lipoic acid is a compound produced by the body that was wide-ranging benefits as an antioxidant and anti-inflammatory substance.
These properties counter many of the problems associated with aging, including heart disease, poor blood sugar control, and being overweight.
Taking ALA as a supplement gives your body access to far higher doses than it would normally produce.
Its safety and proven effectiveness in bolstering overall health make it an excellent candidate for your wellness toolkit.
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La Supplementation Alleviated Inflammation In Fa
Considering the key role of inflammation in FA-induced AKI, we evaluated the release of pro-inflammatory factors and the infiltration of inflammatory cells using IHC staining. The results showed that FA injection markedly enhanced the secretion of TNF- and IL-1 in the tubular epithelium, together with the increased infiltration of macrophage in the interstitial space, whereas LA supplementation downregulated the levels of these molecules. To corroborate our IHC data, western blotting experiments for TNF- and IL-1 showed that their expressions were significantly increased after FA injection, which were alleviated by LA supplementation but without significant difference between the two dose groups, shown in Figure 3.
Here Are Just A Few Of Its Facts:
- Only known antioxidant that is both water and fat soluble
- Clinical studies have shown lipoic acid to be kidney protective
- Significantly reduces symptoms of diabetic neuropathy
- Improves insulin sensitivity improves blood sugar control
- Increases immune function by increasing T lymphocyte production
- Improves energy production via the ATP pathways
- Supports the elimination of heavy metals increased chelation of heavy metals in the liver
- Supports mitochondrial function the energy power houses found mainly within the muscles
- Food sources: broccoli, brewers yeast, brussels sprouts, rice bran, egg yolk, spinach, potatoes, and animal liver, heart, and kidneys
Now before you race off to purchase some, there is just one matter to make sure you have right, and that is making sure you buy the correct type. You see there are three different forms of lipoic acid, and the differences are quite dramatic.
- Choice 1 R-Lipoic Acid: this is the best form, because it is the naturally occurring form of lipoic acid
- Choice 2 Alpha Lipoic Acid: this is the second best form, because it contains a 50:50 blend of the naturally occurring form and the synthetic form
- Choice 3 S-Lipoic Acid: This is the least effective form, containing only the synthetic variety
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How Much Will It Cost You
At present, the entire program is sold at a bargain cost of just $87 for the entire set of cookbooks, ebooks, audiobooks, meditation videos, and much more. For this one-time fee, you will get all future updates free of cost.
The program comes with a 60-day money-back guarantee where you receive a complete refund if youre not satisfied with their product after 60 days.
Youll have instant access to all the materials after paying for the program. The materials come in the form of ebooks, audio, and videos.
What Does Alpha Lipoic Acid Do
I think the better question might be, what doesnt it do!
Heres a bit of an overview of the clinical properties of alpha lipoic acid:
- Anti-obesity agent
- Protects kidneys
Some of the actions of alpha lipoic acid are particularly important when it comes to kidney health, so these are the ones Im going to focus on today.
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Chronic Kidney Disease Stages
The stages of chronic kidney disease include:
The following table outlines the characteristics of each chronic kidney disease stage.
Brain Function And Stroke
Because alpha-lipoic acid can pass easily into the brain, it may help protect the brain and nerve tissue. Researchers are investigating it as a potential treatment for stroke and other brain problems involving free radical damage, such as dementia. So far, there’s no evidence to say whether or not it works.
The Role Of Pi3k/akt Pathway In Anti
The PI3K/Akt pathway plays a key role in inflammation. In animal models of IRI of the kidney and intestine, erythropoietin has been shown to have significant protective effects of IRI. In a rat model of myocardial IRI, pretreatment of erythropoietin led to significant decrease in the levels of proinflammatory cytokines . The effects of EPO were found to be associated with the activation of PI3K/Akt signaling, which suppressed the inflammatory responses . Similarly, in a rat model with severe acute pancreatitis, Akt expression in pancreas was significantly increased, along with the activation of cytokines . The administration of wortmannin reduced Akt expression, NF-B and p38MAPK expression associated with attenuation of the level of inflammation factor, suggesting that the anti-inflammation property of the PI3K/Akt pathway results in the suppression on NF-B and p38MAPK activity .
Who Created This Program Kidney Disease Solution Program
The Kidney Disease Solution was created by Duncan Capicchiano and his wife, Fiona Chin, from Melbourne, Australia. They started a wellness clinic in Melbourne with more than 13 health professionals who are natural.
Fully qualified Naturopaths and Naturopaths, they have a common background in herbal and natural medicine.
The program began as an alternative method of treatment for Fionas grandmother, diagnosed with stage-4 renal disease. The couple developed an all-natural program which helped improve her condition in only 12 weeks. After 6 months her health changed from stage 4 to stage 1 and she was able to live a healthy life for the next 10 years.
Due to the success they have had with Fionas grandmother They decided to start a company and share their approach to treatment with people who are suffering from kidney diseases.
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Ala Ameliorates The Uuo
During EMT in the kidney, the integrity of the tubular basement membrane is gradually destroyed, in a process that includes the up-regulation of matrix proteinases. Both MMP-2 and MMP-9 participate in EMT-mediated obstructive nephropathy,. ALA inhibited MMP-9 expression in smooth muscle cells from the thoracic aorta. In the UUO kidneys, both MMP-2 and MMP-9 were expressed in the epithelial cells of the dilated tubules and occasionally in interstitial areas adjacent to the dilated tubules whereas their expression was reduced by ALA .
Figure 6: ALA decreases the expression of MMP-2 and MMP-9.
Immunohistochemical staining was performed with a specific antibody against MMP-2 and MMP-9 . Densitometric quantification for MMP-2 and MMP-9 was applied to each group. ALA only ALA treated group, ALA+Sham ALA treated and no ureteral ligated group, UUO no ALA treated, but ureteral ligated group, UUO+ALA ALA treated and ureteral ligated group. Values are expressed as means±SE . Scale bar 50m. Asterisk, the dilated tubules. UUO1, enlarged image from insert in UUO. Arrow, tubular interstitial area. Asterisk, the dilated tubules.
Immunohistochemical Analysis Of Icam
Immunohistochemical staining for ICAM-1, MCP-1 and NF-B p65 was performed as previously described . In brief, isolated kidney tissues were fixed by immersion in 4% paraformaldehyde and embedded in paraffin. The tissue sections were then deparaffinized with xylene and rehydrated with ethanol. After treatment with the blocking buffer, the slides were incubated overnight at 4°C with either a hamster anti-mouse ICAM-1 antibody , a rabbit anti-mouse MCP-1 antibody or a rabbit polyclonal antibody directed against NF-B p65 . The kidney sections were exposed to DAKO Chromogen to visualize the immunocomplexes and counterstained with haematoxylin . All of the slides were evaluated by two blinded observers using a Zeiss Z1 microscope . The extent of ICAM-1 and MCP-1 immunostaining in kidney tissue was expressed as a percentage of the area of 10 random, non-overlapping fields per slide at a magnification of ×400 using a digital image analysis program . The numbers of NF-B-activated cells in each section were calculated by counting the number of positively stained cells in 10 random and non-overlapping fields per slide at a magnification of ×400.
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Is Alpha Lipoic Acid Good For Blood Circulation
Because of its antioxidant properties1 and its ability to improve blood-vessel circulation to the nerves,2 ALA has received significant attention as a possible treatment for diabetic peripheral neuropathy, and it has been used in Germany for decades as a treatment for this painful and dangerous complication.
The Role Of Pi3k/akt Pathway In Myocardial Preconditioning And Iri
In acute IPC, Akt/PKB activation resulting in cardioprotection by IPC may be attributed to enhancement of cellular survival and metabolic shifts by Akt/PKB stimulation and/or inhibition of glycogen synthase kinase 3 in response to phosphorylation increased by IPC . The IPC-mediated cardioprotection is primarily via the activation of the PI3K-PKB/Akt reperfusion injury salvage kinase pathway, in which enhanced phosphorylation of Akt/PKB and GSK3 exert better functional recovery and reduces cell death .
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Exercise And Kidney Health
Research has demonstrated several benefits of physical activity for individuals with CKD. A recent meta-analysis found that aerobic exercise is associated with improved cardiorespiratory function, exercise duration, high-density lipoprotein cholesterol levels, and quality of life in patients with CKD. Physical activity can also contribute to prevention by improving metabolic risk factors, which may support healthy kidney function.
What Happens If I Take Too Much Alpha
Since ALA is not an essential nutrient, there is no recommended amount to get in your diet or through supplements. There also is no set upper intake limit. If you take too much ALA, you may experience some of the side effects discussed above, but they tend to resolve when the supplement is stopped.
Otherwise, one reported case of a 70-year-old woman who experienced multiple organ failures from too much ALA. But this was partially caused by a prescribing error. Accidental exposure to ALA caused one toddler to experience convulsions. In general, it is important to keep all medications and supplements out of the reach of children and pets to avoid accidental ingestion.
Additionally, a 22-year-old woman was admitted to an emergency department after an intentional overdose of ALA. She presented with tachycardia or a rapid heartbeat, altered mental state, metabolic acidosis, and an abnormal electrocardiogram . She was treated and discharged from the hospital three days later.
In nonhuman animal studies, high levels of ALA were reported to cause changes in liver function, alteration in liver enzymes, apathy, and confusion. While we canât conclude toxicity using nonhuman animal studies alone, it may be worth considering when frequently taking high doses of ALA.
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