Figure 7 - uploaded by Wai W Cheung
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Fatty infiltration in skeletal muscle was reduced with repletion of 25-hydroxyvitamin D3 in Ctns −/− mice. Visualization of the quantification of fatty infiltration by Oil Red O analysis in the gastrocnemius muscle (A-F). Final results were expressed in arbitrary units, with one unit being the mean staining intensity in WT + Vehicle mice (G). Results are expressed and analyzed as in Figure 1. * p < 0.05, *** p < 0.001.
Source publication
Manifestations of infantile nephropathic cystinosis (INC) often include cachexia and deficiency of circulating vitamin D metabolites. We examined the impact of 25(OH)D3 versus 1,25(OH)2D3 repletion in Ctns null mice, a mouse model of INC. Six weeks of intraperitoneal administration of 25(OH)D3 (75 μg/kg/day) or 1,25(OH)2D3 (60 ng/kg/day) resulted i...
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Citations
... Vitamin D supplementation is often given to patients as rickets prevention. 25(OH)D 3 demonstrated an advantage over 1,25(OH) 2 D 3 by preventing muscle atrophy and adipose tissue browning in an experimental study with Ctns −/− mice [108]. Furthermore, an experimental study has demonstrated the involvement of IL 1 in cystinosis metabolic bone disease, potentially giving a role to immunosuppressive therapy in the cystinosis management [42]. ...
Cystinosis is a rare autosomal recessive disease characterised by an accumulation of cystine in the lysosomes. It is caused by pathogenic variants of the cystinosin gene ( CTNS ), which interrupts the transport of cystine from the lysosomes into the cytosol. Intra-lysosomal cystine accumulation leads to subsequent cellular dysfunction. Cystinosis has an incidence of 0.5–1/100,000 live births. There are three forms of cystinosis: nephropathic cystinosis, juvenile cystinosis, and ocular cystinosis, with nephropathic cystinosis being the most prevalent disease subtype. Renal impairment is the most common manifestation of disease. Extrarenal manifestations of cystinosis include hypothyroidism, diabetes, and hypogonadism. The current treatment for cystinosis is cysteamine, a cystine-depleting agent. This is not a curative treatment and only aims to slow the progression of disease. A total of 90% of cystinosis patients progress to kidney failure within the first 20 years of life. Kidney transplantation is the only option available to patients once the disease has progressed to this stage. This review highlights the pathogenesis and clinical manifestations of cystinosis, as well as potential future treatment options.
... 1,25(OH) 2 D 3 supplementation reduced muscle protein catabolism by reversing oxidative stress and restoring antioxidant enzyme levels [92]. More recently, Zhou and colleagues [93] reported that the administration of 25(OH)D 3 , but not 1,25(OH) 2 D 3 , enhanced muscle fiber size and decreased the fat infiltration of skeletal muscle in Ctns knockout mice, an animal model of cystinosis. Therefore, more research is required to determine the role of the two vitamin D forms, 25(OH)D 3 and 1,25(OH) 2 D 3 , in individuals with cachexia due to CKD. ...
Redox signaling alterations contribute to chronic kidney disease (CKD)-associated cachexia. This review aims to summarize studies about redox pathophysiology in CKD-associated cachexia and muscle wasting and to discuss potential therapeutic approaches based on antioxidant and anti-inflammatory molecules to restore redox homeostasis. Enzymatic and non-enzymatic systems of antioxidant molecules have been studied in experimental models of kidney diseases and patients with CKD. Oxidative stress is increased by several factors present in CKD, including uremic toxins, inflammation, and metabolic and hormone alterations, leading to muscle wasting. Rehabilitative nutritional and physical exercises have shown beneficial effects for CKD-associated cachexia. Anti-inflammatory molecules have also been tested in experimental models of CKD. The importance of oxidative stress has been shown by experimental studies in which antioxidant therapies ameliorated CKD and its associated complications in the 5/6 nephrectomy model. Treatment of CKD-associated cachexia is a challenge and further studies are necessary to investigate potential therapies involving antioxidant therapy.
