The urinary system, often referred to as the renal system or the urinary tract, oversees maintaining blood pressure and volume, eliminating waste from circulation in the form of urine, and managing the concentrations of salts and chemicals in the body's cells and blood. This complex system, which includes the bladder, urethra, ureters, and kidneys, is essential to sustaining general health.
Urinary System Overview
The most important organs in the urinary system, the kidneys, filter blood and create urine. They control blood pressure, salt levels, and the body's acid-base balance in addition to getting rid of waste. Pee is transported via the ureters from the kidneys to the bladder, which acts as a holding tank until the urethra is used to release the pee. The functioning of the urinary system is critical to general health, underscoring the significance of seeking medical assistance as soon as there is a change in the frequency or flow of urine.
Kidney Diseases
The common disorder known as chronic kidney disease (CKD) impairs the kidneys' capacity to remove waste products from the blood. Two-thirds of instances of chronic kidney disease (CKD) are caused by diabetes and high blood pressure; glomerulonephritis, polycystic kidney disease, infections, autoimmune illnesses, and nephrotoxic medications are among the other reasons. The fact that CKD symptoms can not appear until later in the disease emphasizes how crucial routine checkups with a doctor are. A continuous decrease in the glomerular filtration rate (GFR) and the existence of proteinuria or albuminuria are the hallmarks of chronic kidney disease (CKD).
It is a separate risk factor for cardiovascular problems as well as end-stage renal disease (ESRD), which lowers quality of life and increases mortality risk. Acute kidney damage (AKI), which has a significant risk of death, is also common in critical disease circumstances. Moreover, AKI can exacerbate pre-existing CKD and increase the risk of incident CKD development. It can also directly lead to ESRD. Consequently, more measures must be implemented to prevent acute and chronic kidney damage.
Causes and Symptoms of CKD
Dialysis or kidney transplantation may be required if kidney failure results from diabetes and high blood pressure, two common causes of chronic kidney disease (CKD). Advanced chronic kidney disease (CKD) is indicated by symptoms such as weakness, weariness, lack of appetite, trouble concentrating, leg oedema, and changes in the urine. Depending on the disease's stage, medicine, dialysis, transplantation, and lifestyle modifications are all effective forms of therapy, even though there is no known cure.
Resveratrol
Natural polyphenol resveratrol is present in red wine, grapes, and other plant sources. It has drawn a lot of interest because it may help obese people lose weight and control their Type 2 Diabetes Mellitus (T2DM). We shall examine resveratrol's physiological function, advantages, and effects on obesity and type 2 diabetes in this post. We will also go over the results of pre-clinical and clinical studies that provide insight into resveratrol's potential as a treatment for certain ailments.
A stilbenoid is a polyphenolic molecule that includes resveratrol. Plants naturally produce it in response to a variety of stresses, including damage, fungal infections, and UV radiation exposure. Due to its correlation with red wine and the "French Paradox," which describes the minimal risk of heart disease among French people while eating a diet high in saturated fats, resveratrol has gained significant interest. Resveratrol helps plants become more resilient overall by acting as a shield against environmental stresses. Resveratrol has anti-ageing, anti-inflammatory, and antioxidant effects in animals. Its capacity to activate sirtuins, a family of proteins essential for controlling several cellular functions, is thought to be the cause of these effects [1].
Over 70 plant species contain resveratrol, a naturally occurring polyphenol that is a member of the stilbenoids group. The main sources of resveratrol are the skin and seeds of grapes. Resveratrol, which is found in red wines and other foods, functions as a phytoalexin to fight infections such as fungus and bacteria. It has been thoroughly investigated and has strong antioxidant and anticancer effects, suggesting that it might be used as a therapy or preventative for cancer. Numerous beneficial benefits of resveratrol have been shown, such as its anti-inflammatory, cardioprotective, and neuroprotective qualities. Still, its low bioavailability, side effects, and poor solubility provide problems for pharmaceutical use.
Benefits
Numerous health advantages of resveratrol have been studied scientifically, including:
· Antioxidant Properties: Resveratrol functions as an antioxidant to shield cells from free radical-induced oxidative damage. Its capacity to prevent different illnesses and have anti-ageing benefits may be attributed to this feature.
· Anti-Inflammatory Effects: Research has shown that resveratrol has anti-inflammatory qualities, which lower inflammation and the chance of chronic illnesses linked to it.
· Cardiovascular Health: By encouraging blood vessel dilatation, lowering blood pressure, and preventing blood clot formation, resveratrol may contribute to improved cardiovascular health.
· Neuroprotective Effects: Research indicates that resveratrol may shield nerve cells from harm, which may help with diseases such as Alzheimer's [2].
Resveratrol's Potential in Kidney Diseases
Berries and grapes contain a polyphenol called resveratrol, which has drawn interest due to its many health advantages, including its use in renal disorders. According to studies, resveratrol protects the kidneys by lowering inflammation and oxidative stress, two factors that are crucial in the advancement of kidney disease. Furthermore, resveratrol may postpone the ageing of the kidneys, providing a target for preventative measures.
Through a variety of methods, resveratrol (RSV) has a complex effect on metabolic syndrome. By raising HDL cholesterol and lowering LDL and triglyceride levels, it improves the plasma lipid profile. RSV reduces plasma LDL cholesterol via increasing hepatocytes' HMG-CoA reductase activity and encouraging the development of LDL receptors. Furthermore, RSV prevents the migration of vascular smooth muscle cells, which have significant antiatherogenic and antiatherosclerotic properties. RSV reduces the production of TNFα by activating Nrf2, endothelial nitric oxide synthase, and other components of the antioxidant response, exhibiting antioxidative and anti-inflammatory properties.
Additionally, RSV alters the Keap1 protein to stop it from enclosing Nrf2 in the cytoplasm, which stimulates the transcription of many genes involved in antioxidant defence RSV inhibits the NF-κB activation pathway in the vascular endothelium, which lowers the expression of adhesion molecules. Moreover, RSV reduces the development of foam cells in vascular macrophages by blocking nitric oxide synthase 1 and lowering the synthesis of monocyte chemoattractant protein 1. By controlling the renin/angiotensin II system and activating the angiotensin-converting enzyme 2/mas receptor axis, RSV also prevents vascular ageing while also having anti-carcinogenic and cardioprotective properties [3].
Role of Resveratrol in Kidney Function
· Resveratrol also targets genes that are anti-inflammatory and antioxidant through gene regulation. Resveratrol has been shown in animal experiments to be effective in reducing oxidative stress-mediated fibrosis in rats fed a high-fat diet. Nevertheless, further investigation is required to pinpoint the specific genes that resveratrol targets in kidney disorders, underscoring the need for clinical studies to clarify its effects in people.
· By exhibiting antioxidative actions and modifying antioxidant enzymes, resveratrol shows remarkable efficiency in reducing diabetic nephropathy. Resveratrol has been shown in diabetic animal models to decrease the excretion of urine proteins, enhance renal function, and mitigate oxidative stress. This is accomplished by several methods, including SIRT1 or AMPK activation, antioxidant enzyme regulation, and direct radical scavenging. Furthermore, resveratrol inhibits the JNK/NF-B/NADPH oxidase/ROS pathway, preventing diabetic nephropathy. The chemical has a complex activity that includes phosphorylating AMPK and SIRT1-peroxisome proliferator-activated receptor coactivator (PGC)-1 signaling, activating AMPK, and preventing mesangial cell death associated with lipotoxicity.
· Resveratrol shows protective benefits in drug-induced renal damage models by lowering oxidative stress, suppressing inflammation, and attenuating symptoms of renal injury, especially when combined with cisplatin. It has been demonstrated that resveratrol-induced SIRT1 activation lowers cisplatin-induced p53 acetylation, apoptosis, and cytotoxicity. Because of its antioxidative qualities, resveratrol also shows promise in preventing kidney damage brought on by glycerol, gentamicin, and cyclosporine.
· Resveratrol acts via activating the SIRT1/PGC-1α axis in mitochondria, which attenuates the podocyte damage caused by aldosterone that contributes to proteinuria kidney disease. The substance shows promise in treating some renal ailments because it inhibits aldosterone-induced podocyte apoptosis, loss of slit diaphragm proteins, and mitochondrial dysfunction.
· Resveratrol protects against ischemia-reperfusion damage by boosting endothelial NOS (eNOS) activity, inducing the SIRT1/FOXO1 pathway, and decreasing oxidative stress. Resveratrol increases survival rates in mouse models of cecal ligation and puncture (CLP), scavenges reactive nitrogen species, and improves renal microcirculation in sepsis-induced AKI.
· One potentially effective strategy to prevent age-related kidney damage is resveratrol. Resveratrol addresses reduced SIRT1 activity and ageing-related mitochondrial damage by restoring autophagy, and renal function, and reducing histological renal fibrosis in elderly kidneys. This emphasizes resveratrol's capacity to delay the ageing of the kidneys [4].
Pre-clinical and Clinical Trials of Resveratrol in Kidney Diseases
Resveratrol has been demonstrated in pre-clinical research to protect the kidneys by decreasing inflammation and oxidative stress, decreasing senescent cells, and enhancing kidney structure and function in animal experiments. Clinical studies have also looked at resveratrol's advantages for renal disorders.
Resveratrol has been shown to marginally enhance renal function in the general adult population, according to a comprehensive review and meta-analysis of randomized controlled clinical studies. The study did point out that the evidence was of low quality, highlighting the necessity for more high-quality research to corroborate the results. In patients with chronic kidney disease, resveratrol administration was linked to the restoration of renal function and several inflammatory biomarkers, including TNF and IL-6, according to another research. The study also showed that resveratrol had no notable side effects and was well tolerated. These results point to resveratrol as a treatment for chronic renal disease.
The putative pharmacological potential of resveratrol in postponing kidney ageing was covered in a recent review study. According to the paper, resveratrol may lessen renal damage, myocyte hypertrophy, cellular senescence, oxidative stress, tubular atrophy, and interstitial fibrosis. It also increases the binding between FoxO1 and SIRT1. The paper also mentioned the possibility of resveratrol as a treatment for age-related kidney disorders, including diabetic nephropathy and chronic kidney disease. The paper did, however, emphasize the need for more investigation to pinpoint the precise mechanisms of action and possible therapeutic benefits of resveratrol in renal disorders.
A study looks at the underlying mechanism of action of resveratrol and its anti-inflammatory effects in polycystic kidney disease (PKD). Resveratrol therapy significantly decreased kidney weight ratio, cyst volume density, blood urea nitrogen and creatinine levels in male Han: SPRD (Cy/+) rats with PKD. The research further demonstrated a reduction in pro-inflammatory markers and macrophage infiltration in cystic kidneys treated with resveratrol, which was linked to the suppression of the nuclear factor κB (NF-κB) signaling pathway. These results supported the potential of resveratrol to reduce inflammation in PKD by modulating the NF-κB pathway in human autosomal dominant PKD cells. According to the study, resveratrol-based inflammatory targeting may be a viable approach for treating Parkinson's disease in the future [5].
Another study examines how resveratrol supplementation affects the expression of nuclear factor-κB (NF-κB) and nuclear erythroid 2-related factor 2 (Nrf2) in individuals with non-dialyzed chronic kidney disease (CKD). In a pilot study with 20 non dialyzed CKD patients, resveratrol—known for its anti-inflammatory and antioxidant qualities—did not show any discernible effects on proinflammatory cytokines, Nrf2 and NF-κB expression, or antioxidant enzymes. The study, which used 500 mg of resveratrol per day for four weeks, indicates that more studies with different dosages and lengths of treatment are required to fully comprehend the possible anti-inflammatory and antioxidant benefits of resveratrol supplementation in patients with chronic kidney disease [6].
The effect of resveratrol (RSV) on ischemia-reperfusion (I/R) injury in rat kidneys is examined in a different study. I/R injury is a major contributing factor to both acute renal failure and organ rejection following transplantation. Utilizing a rat paradigm in which 20 rats were given RSV before the clamping of both renal arteries for 40 minutes, the study used computerized morphometric analysis to evaluate kidney shape. RSV pretreatment showed protective benefits, preventing I/R-induced glomerular collapse and preserving tissue. In comparison to the I/R group, the RSV group showed improvements in tubular hypertension markers as well as a decrease in platelet clots and tubular necrosis. The administration of l-NAME exacerbated the damage, highlighting RSV's positive benefits. RSV also raised urine levels of cGMP, demonstrating its diverse protective mechanisms against I/R damage to rat kidneys [7].
In conclusion, research on the possible advantages of resveratrol in renal illnesses has been done through pre-clinical and clinical studies. Resveratrol has been demonstrated in pre-clinical research to protect the kidneys by decreasing inflammation and oxidative stress, decreasing senescent cells, and enhancing kidney structure and function in animal experiments. Resveratrol may also be able to treat chronic kidney disease by enhancing renal function and lowering inflammatory biomarkers, according to clinical research. To validate the results and ascertain the precise mechanisms of action and possible therapeutic benefits of resveratrol in renal disorders, additional excellent research is necessary.
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