ascorbic-acid and Rhabdomyolysis

Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease or end-stage kidney disease. An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who developed AKI during COVID-19. The goal of this article is to provide our current understanding of the etiology and the pathophysiology of AKI in the setting of COVID-19.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Antiviral Agents; Apolipoprotein L1; Ascorbic Acid; Azotemia; COVID-19; COVID-19 Drug Treatment; Cytokines; Disease Progression; Glomerulonephritis; Glomerulonephritis, Membranous; Hospital Mortality; Humans; Kidney Tubules, Proximal; Length of Stay; Myoglobin; Nephritis, Interstitial; Nephrosis, Lipoid; Renal Insufficiency, Chronic; Rhabdomyolysis; SARS-CoV-2; Severity of Illness Index; Thrombotic Microangiopathies; Vitamins

Acute kidney injury causes significant morbidity and mortality in the community and clinic. Various pathologies, including renal and cardiovascular disease, traumatic injury/rhabdomyolysis, sepsis, and nephrotoxicity, that cause acute kidney injury (AKI), induce general or regional decreases in renal blood flow. The ensuing renal hypoxia and ischemia promotes the formation of reactive oxygen species (ROS) such as superoxide radical anions, peroxides, and hydroxyl radicals, that can oxidatively damage biomolecules and membranes, and affect organelle function and induce renal tubule cell injury, inflammation, and vascular dysfunction. Acute kidney injury is associated with increased oxidative damage, and various endogenous and synthetic antioxidants that mitigate source and derived oxidants are beneficial in cell-based and animal studies. However, the benefit of synthetic antioxidant supplementation in human acute kidney injury and renal disease remains to be realized. The endogenous low-molecular weight, non-proteinaceous antioxidant, ascorbate (vitamin C), is a promising therapeutic in human renal injury in critical illness and nephrotoxicity. Ascorbate may exert significant protection by reducing reactive oxygen species and renal oxidative damage via its antioxidant activity, and/or by its non-antioxidant functions in maintaining hydroxylase and monooxygenase enzymes, and endothelium and vascular function. Ascorbate supplementation may be particularly important in renal injury patients with low vitamin C status.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Dietary Supplements; Humans; Kidney; Oxidants; Oxidative Stress; Reactive Oxygen Species; Rhabdomyolysis

We investigated whether cosupplementation with synthetic tetra-tert-butyl bisphenol (BP) and vitamin C (Vit C) ameliorated oxidative stress and acute kidney injury (AKI) in an animal model of acute rhabdomyolysis (RM). Rats were divided into groups: Sham and Control (normal chow), and BP (receiving 0.12% w/w BP in the diet; 4 weeks) with or without Vit C (100mg/kg ascorbate in PBS ip at 72, 48, and 24h before RM induction). All animals (except the Sham) were treated with 50% v/v glycerol/PBS (6 mL/kg injected into the hind leg) to induce RM. After 24h, urine, plasma, kidneys, and aortae were harvested. Lipid oxidation (assessed as cholesteryl ester hydroperoxides and hydroxides and F(2)-isoprostanes accumulation) increased in the kidney and plasma and this was coupled with decreased aortic levels of cyclic guanylylmonophosphate (cGMP). In renal tissues, RM stimulated glutathione peroxidase (GPx)-4, superoxide dismutase (SOD)-1/2 and nuclear factor kappa-beta (NFκβ) gene expression and promoted AKI as judged by formation of tubular casts, damaged epithelia, and increased urinary levels of total protein, kidney-injury molecule-1 (KIM-1), and clusterin. Supplementation with BP±Vit C inhibited the two indices of lipid oxidation, down-regulated GPx-4, SOD1/2, and NF-κβ gene responses and restored aortic cGMP, yet renal dysfunction and altered kidney morphology persisted. By contrast, supplementation with Vit C alone inhibited oxidative stress and diminished cast formation and proteinuria, while other plasma and urinary markers of AKI remained elevated. These data indicate that lipid- and water-soluble antioxidants may differ in terms of their therapeutic impact on RM-induced renal dysfunction.

Topics: Animals; Ascorbic Acid; Base Sequence; Biomarkers; Blood Vessels; DNA Primers; Kidney Diseases; Lipids; Male; Models, Animal; Oxidative Stress; Polyphenols; Rats; Rats, Wistar; Rhabdomyolysis

Topics: Acetylcysteine; Acute Kidney Injury; Adult; Ascorbic Acid; Charcoal; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Diuretics; Fatal Outcome; Furosemide; Gastric Lavage; Hemoperfusion; Humans; Immunosuppressive Agents; Male; Paraquat; Poisoning; Pulmonary Fibrosis; Respiration, Artificial; Respiratory Insufficiency; Rhabdomyolysis; Suicide, Attempted; Vitamin E

During times of war and natural disasters, rhabdomyolysis-induced myoglobinuric acute renal failure (ARF) can assume epidemic proportions. Free radicals play an important role in the pathogenesis of myoglobinuric ARF. Vitamin C is a major antioxidant, scavenging free radicals. We have not found any studies on the effect of vitamin C on myoglobinuric ARF. Thus, we aimed to investigate the effects of vitamin C on the myoglobinuric ARF formed by glycerol in rats. Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (10 mL/kg, i.m.), and group 3 was given glycerol plus vitamin C (20 mg/kg, i.p. for four days). Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma; N-acetyl-beta-D-glucosaminidase activity in urine; malondialdehyde levels, superoxide dismutase and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress and severe renal functional and morphological deterioration. The treatment of animals with vitamin C partially corrected the renal dysfunction and morphological impairment. In this respect, vitamin C appears to be a promising candidate for the prevention of rhabdomyolysis-induced ARF. Higher dosages of vitamin C than in 20 mg/kg may be beneficial for better functional and morphological recovery in this model ARF.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Biopsy, Needle; Disease Models, Animal; Glycerol; Immunohistochemistry; Kidney Function Tests; Kidney Tubular Necrosis, Acute; Male; Malondialdehyde; Myoglobinuria; Probability; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Rhabdomyolysis; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

Topics: Acute Kidney Injury; Antioxidants; Ascorbic Acid; Humans; Hydrogen-Ion Concentration; Myoglobin; Oxidation-Reduction; Rhabdomyolysis; Urinalysis