When The Gonads Talk To The Heart: Potential Mechanisms Of Action
Testosterone may indirectly relate to cardiovascular complications by its association with risk factors such as dyslipidaemia, obesity, diabetes, metabolic syndrome or old age, which may contribute to endothelial dysfunction and atherosclerosis. Nevertheless, testosterone seems to play a role per se in lipid metabolism by affecting lipoprotein lipase and lipolysis, and in several disease populations, testosterone supplementation has resulted in modest reductions of both total and LDL cholesterol without affecting triglycerides . A recent meta-analysis reported a small, but significant, decrease in HDL cholesterol as well . Hypogonadism may also indirectly impact on cardiovascular health via insulin sensitivity, which seems improved after testosterone supplementation in Type-2 diabetic patients .
Univariate associations between serum testosterone and IL-6 among 260 ESRD men. Reproduced from Carrero et al. .
Transwell Assay For Rmc Cells
The transwell method was carried out as previously reported by Peng et al.. The dose of Bic was 30M in parallel with TGF- at a dose of 5ng/ml as the positive control. In brief, 1 day before the experiment, a sufficient number of cells was inoculated in DMEM containing 2% charcoal-treated FBS on a 24-well plate with inserts. A density of 105 cells /mL was seeded in the insert and incubated in the incubator for 72h until cells were adherent. When the set time was reached, the inserts were taken out, medium remaining inside was removed, and inserts were blotted with a PBS-wetted cotton plug. Inserts were immersed in 10% formalin for at least 20min and then rinsed with PBS. The treated inserts were dipped in an eosin solution for at least 30min and rinsed several times with double-distilled water . Inserts were immersed in a hematoxylin solution for at least 30min and then rinsed several times with ddH2O. Micrographs were observed with a light microscope at a magnification ×200. Five-fields examined in each group. The number of transwell cells was counted from photos. The experiment was performed in triplicate.
How Our Body Breaks Down Creatine
1. The skeletal muscles, brain, and other muscles in our body store the creatine you take as supplements.
2. The muscles break down the ingested creatine into phosphocreatine and use it to replenish the ATP.
3. The process creates a byproduct called creatinine.
Now, the kidneys excrete creatinine as it is. And this is where all the misconception begins!
Our bodies produce creatinine in response to various events.
For instance, your creatinine levels may rise if you have more muscle mass. Or, you may have high creatinine levels if you consume more animal protein.
Most importantly, your kidneys also produce more creatinine if they are damaged or impaired.
So, high creatinine levels are a marker of kidney disease.
Doctors use blood and urine tests to determine creatinine levels for diagnosing liver or kidney diseases.
Taking these supplements in excess of what your muscles can store may increase your creatinine levels. Your body breaks down more phosphocreatine and produces more creatinine.
But increased levels of creatinine doesnt always mean kidney problems. You can have high creatinine levels for different reasons and still have healthy kidneys.
So even if creatine supplements may raise your creatinine levels, it doesnt damage the kidneys.
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Testosterone Deficiency And Bone Health
Testosterone plays an important role in bone mineral density by increasing osteoblastic activity and reducing osteoclastic activity and in ageing men, there is a strong association between low testosterone and bone loss . Conversely, the osteoblast-derived hormone osteocalcin, in addition to its endocrine role as a regulator of energy homeostasis, favours male fertility by promoting testosterone synthesis by Leydig cells in the testes . Although no intervention study has yet been large enough to demonstrate a reduction in fracture risk with testosterone supplementation, a meta-analysis suggested that testosterone replacement positively affects bone density and reduces bone loss . A small study of men undergoing HD reported that testosterone correlated negatively with sRANKL concentrations, and the authors proposed that RANKL might mediate the effect of testosterone on bone metabolism in these patients . No studies have addressed the impact of testosterone deficiency on uraemic bone status.
What Hormones Do The Kidneys Produce
The kidneys make two main hormones, vitamin D and erythropoietin.
Vitamin D is essential for a number of different functions in the body. Most of the vitamin D that is in the blood is inactive and it is modified by the kidney and other tissues to activate it. Active vitamin D stimulates the uptake of calcium from food, is important for the maintenance of healthy bones and also helps to regulate the response of the immune system to infection.
Erythropoietin is produced when oxygen levels in the blood are low. It acts in bone marrow to stimulate the production of mature red blood cells, to maintain healthy oxygen levels in our tissues.
The kidneys also produce prostaglandins, hormone-like substances, made from lipid . The substances are one way in which the production of renin is stimulated. Renin is an enzyme, also produced by the kidneys, that plays an important role in the reninangiotensinaldosterone hormonal system, which helps to control blood pressure. In addition to making hormones, the kidneys also respond to a number of hormones including vitamin D, aldosterone, prostaglandins, cortisol, parathyroid hormone and calcitonin.
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Alkylated Oral Steroids Vs Non
The risk of serious kidney and liver damage is higher with oral alkylated steroids than non alkylated injectable steroids. The increased hepatotoxicity of orals is due to their chemical structure has been modified.
Why does it need to be modified? Because of the journey it needs to take.
The Journey of the Oral Steroid
When you take an oral steroid its absorbed by the digestive system and then taken to the liver for processing.
For the body to absorb the anabolic properties of oral steroids they need to pass through the liver without being broken down and metabolized.
To make oral steroids more bio-available scientists modified the chemical structure of synthetic testosterone.
The modification known as 17 alpha alkylation simply adds an extra alkyl group to the 17th carbon of the steroids DNA. This makes orals more resistant to being metabolized by the liver.
Non-alkylated steroids or a non altered forms of synthetic of testosterone and wouldnt survive this journey this is why theyre injected directly into the blood stream.
However, by making C17- alpha alkylated oral steroids more bio-degradable also makes them more hepatoxic because their greater resistance to being broken down puts more stress on the liver.
Which Steroids are Alpha Alkylated and Non Alkylated?
C17 Alpha Alkylated Oral Steroids
- Dianabol
- Primobolan
How Does Testosterone Harm Your Kidneys If You Have High Blood Pressure
Since testosterone stimulates red blood cell production and lowers LDL cholesterol levels, it can improve or hinder circulation, depending on its levels. People with Low T are more likely to suffer from anemia and atherosclerosis, increasing the risk of cardiovascular disease. Because the kidneys use blood vessels to filter waste, they need these blood vessels to be in proper working order. Low testosterone can lead to plaque build up of cholesterol in the arteries, causing atherosclerosis and hardening or narrowing of the arteries. Blood flow to the kidneys decreases so that kidney arteries cannot filter the blood properly. Eventually, the kidneys begin to fail.
Although the effects may be somewhat indirect, low testosterone can result in problems with the kidneys.
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Testosterone Replacement May Delay Ckd Progression
ORLANDO, Fla.Testosterone replacement therapy may delay progression of chronic kidney disease and lower the risk of death in men with hypogonadism, new findings presented at the National Kidney Foundations 2017 Spring Clinical Meetings suggest.
Archana Goel, MD, of the Veterans Administration Medical Center in Kansas City, Missouri, and colleagues analyzed data from a large cohort of veterans diagnosed with low total testosterone . The investigators divided patients into 2 groups: those treated and who had normalization of TT and those who were not treated and continued to have low TT. The treated and untreated groups had follow-up times of 6.1 and 5.1 years, respectively.
The groups did not differ significantly in the number of days until patients had a 30% or greater increase in serum creatinine or doubling of serum creatinine from baseline, the investigators reported in a poster presentation. The treated group, however, showed a significant delay in the progression of CKD as measured by days to serum creatinine increases of 1.5 or higher and 3.0 mg/dL or higher. TRT delayed the time to end-stage renal disease , as defined by a serum creatinine level greater than 6.0 mg/dL) by 284 days and time to death by 328 days. Compared with the untreated men, the treated men had a 24% decreased risk of ESRD and 25% decreased risk of death.
See more coverage from the National Kidney Foundation Spring Clinical meeting.
Cell Cultures And Mtt Assay
The RMC cell line was incubated in modified Dulbeccos Eagles medium containing 4 mM L-glutamine, 1.5g/L sodium bicarbonate, 4.5g/L glucose and supplemented with 0.4mg/mL G418, 15% fetal bovine serum, and 0.4% PBS. NRK52E cells were cultured in DMEM containing 2mM glutamine, 1% non-essential amino acids, 5% fetal bovine serum and 0.4% PBS.
The cells were inoculated onto 24-well plates at a density 1.5×104 cells/well or 3.5×104 cells/well , gently agitated to mix them well, and incubated overnight until completely adherent. The medium was removed and replaced with medicine containing 2% charcoal-treated FBS medium, and treated for 24 and 48h. Doses of testosterone used were 1, 10, 100, and 1000nM, while those of Bic was 3.75, 7.5, 15, 30, and 60M. After cells were challenged with drugs and incubated for 24 and/or 48h, cell viability was measured with MTT and formazan production was determined by the absorbance at 540nm with a multifunctional plate reader . In cases where SC-79 and MK-2206 were applied, cells were pretreated with these modulators, 10M of SC-79 and/or 1M of MK-2206, for 30min before the addition of Bic.
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S To Protect Your Liver
Without a doubt, your liver needs protection when taking oral or methylated steroids.
Heres 5 simple steps to help protect, detoxify and cleanse your liver during and after a bulking cycle.
1: Get your blood checked to ensure your liver enzyme levels are within a healthy range. For example, taking prescription meds or drinking alcohol will elevate levels meaning your liver is already working hard.
2: Abstain from alcohol and prescription meds during and 6 weeks after a cycle.
3:Take a good herbal liver detoxifier before and post cycle.
4: Increase your intake of water water is an effective detoxifier and its free!
5:Reduce your salt intake salt and steroids increases water retention which can lead to hypertension and put further stress on the liver.
The Extrinsic Pathway Upregulated By Bic Is Attenuated By Co
As mentioned, Bic was able to inhibit both the cytosolic and nuclear AR so, we further examined whether testosterone could competitively and efficiently attenuate such a phenomenon and associated signaling pathways. As we found, TNF- and cleaved caspase-3 were all ameliorated by co-treatment with testosterone at a dose of 100nM, and it seemed that TNFR and p-PI3K were not significantly affected by testosterone . In contrast, p-Akt was prominently attenuated at a testosterone dose of 500nM.
Figure 9
Dose dependent effect of co-treatment with testosterone and bicalutamide on the survival and apoptotic pathways in the RMC cells. TNF- and TNFR. Total and phosphorated PI3K, PDGF-R, and Akt. Caspase-3 and cleaved caspase-3. Experiment was performed in triplicate and statistically treated . The symbol * compares within the same group and # compares among groups. *p< 0.05, **p< 0.01, ***p< 0.001. #p< 0.05, ##p< 0.01, ###p< 0.001.
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What Could Go Wrong With The Kidneys
When the kidneys are not working correctly, waste products and excess fluid can build up and the levels of sodium, potassium, phosphate and calcium are not regulated correctly. When these substances gather together, this causes the symptoms of kidney disease, which can include high blood pressure, excessive tiredness, fluid retention and possibly lower back pain.
Kidney damage can occur for a number of reasons diabetes, high blood pressure, infections and a group of diseases that affect the glomerulus. The kidneys also need an adequate supply of blood, so if there is something wrong with the blood vessels to the kidney, such as a narrowing, this will prevent the kidneys from working efficiently.
The Role Of Testosterone In Chronic Kidney Disease And
From the perspective of clinical and public health practice, by negative I mean that in some cases testosterone replacement therapy could actually aggravateSuspecting issues with your kidneys might not be the first thing you do when you hear about low libido, testosterone can affect the kidneys in several counterintuitive ways that most men on HRT may not be aware of, Testosterone effects on kidneys, and excess fluids from the body, If youre male and living with kidney disease or you dont know your level of kidney function, That where majority of damage occurs.Testosterone is classified as an androgenic steroid hormone that is secreted primarily by the testicles in males, One is generally positive and the other generally negative, intramuscular 400 mg nandrolone decanoate and oral 40 mgTestosterone effects on kidneys Sign in to follow this , Stress can be a contributing factor as can any chronic illness.
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Male Enhancement Pills Will Testosterone Damage My Kidneys
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Changes In Testosterone With Age
Several cross-sectional and longitudinal studies documented a decline in total and bioavailable circulating testosterone levels with aging in men. More than 60% of healthy, elderly men over 65 yr of age have free testosterone levels below the normal values of men aged 30â35 yr. Because androgen receptors are upregulated in the presence of androgens and downregulated in its absence, it is likely that a reduction in androgen receptors may occur with aging as well. There have been studies in which the expression of androgen receptors in aging men was reduced in reproductive tissues, but there have been no studies in which the expression of androgen receptors has been studied in nonreproductive tissues in aging individuals. The decrease in androgen levels with aging in men appears to be the result of both gonadal and hypothalamic-pituitary failure and is independent of chronic illness, obesity, or medication . However, chronic illnesses , such as hypertension , diabetes , chronic kidney disease , and end-stage renal disease , are associated with a further reduction in serum testosterone levels in men of all ages. The fact that androgen levels decrease with age have led scientists to presume that androgens do not play a role in chronic cardiovascular and renal disease in aging men. However, growing evidence indicates that testosterone, even at levels observed in aging men, can have adverse consequences on cardiovascular-renal function.
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Areyou At Risk For Kidney Disease
Most people with kidneydisease dont have any symptoms until theyre very sick. So unless your doctorhas tested your kidney function, you cant be sure that you dont have kidneyproblems.
A few simple tests will tellyour doctor how well your kidneys are working. He or she will:
- Check your blood pressure.
- Take a blood sample and test the levels of blood urea nitrogen and creatinine, which are indicators of how well your kidneys are cleaning your blood.
- Take a urine sample to check for blood, infection or protein in your urine.
Even slightly higher thannormal blood pressure or cholesterol increases your risk for kidney disease,stresses Dr. Heyka. So keep your blood pressure, cholesterol and weight incheck, as well as your blood sugar if you have diabetes. And, as always, makesure you tell your doctor about every vitamin, herbal remedy and nutritionalsupplement you take.
Physiology And Natural Course Of Endogenous Testosterone During Lifespan
Since testosterone synthesis is partially suppressed by multiple causes linked to a failing kidney, it is possible that the normal progressive reduction in renal function with age contributes, at least in part, to this natural decline. No studies, to our knowledge, have, however, addressed this issue. The community-based PREVEND cohort suggested that risk factors such as age, BMI and plasma glucose contributed to exacerbating the male progression to ESRD to a greater extent than for comparable women . It may not be coincidence that also ageing, diabetes and increased BMI are also associated with lower testosterone levels .
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The Columbia University Study
A controversial study in 2009 provided the strongest evidence that long term steroid use can damage the kidneys.
The 10 year study by Doctors at Columbia University was presented at the American Society of Nephrology in 2009. It involved 9 bodybuilders and 1 power-lifter who were steroids users and each one had developed permanent damage to their kidneys.
It turns out, 9 of the men developed a condition called Focal Segmental Glomerulosclerosis an irreversible chronic kidney disease that attacks the glomeruli, the kidneys filtering units. BTW, FSGS was the condition that ended Flex Wheelers career.
Your Kidneys And Your Sex Life
For kidney month, were going to take a look at the relationship between your kidneys and your sex life. Suspecting issues with your kidneys might not be the first thing you do when you hear about low libido. But the kidneys can affect sex since kidney disease can cause a low sex drive, among many other things.
Kidney disease can often be silent in thatyou can lose 90% of your kidney function without really experiencing anysymptoms. Yet if you have a decreasing love life, maybe its time to startquestioning if your kidneys are responsible.
Other symptoms of kidney disease include aweakening of your bones, inability to concentrate, swelling in arms or legs, impairedheart function and damage to blood vessels. These symptoms are similar toeveryday aches and pains, and may overlap those of other illnesses. This couldbe one reason why so many people walk around with kidney disease withoutknowing it.
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