Changes of Klotho protein and Klotho mRNA expression in a hydroxy-L-proline induced hyperoxaluric rat model

Abstract

Klotho protein is recognized as having a renoprotective effect and is used as a biomarker for kidney injury. We investigated the level of Klotho protein in hyperoxaluria-induced kidney injury and the effects of vitamin E (Vit E) and vitamin C (Vit C) supplementation. Hyperoxaluria was induced by feeding 2% (w/v) Hydroxy-L-proline (HLP) in the drinking water for 21 days. Rats were divided into 5 groups; control (Group 1, n=7), HLP treated rats that received nothing else (Group 2, n=7), Vit E (Group 3, n=6), Vit C (Group 4, n=6) and both Vit E and Vit C (Group 5, n=7). Vit E (200 mg/kg) was injected on days 1, 6, 11 and 16, while Vit C (500 mg/kg) was given intravenously on days 1 and 11. The Klotho protein levels and oxidative status were measured. The expression level of kidney Klotho protein expression was significantly reduced by HLP-treatment, while the mRNA expression was higher (P<0.05), the plasma and kidney malondialdehyde and kidney superoxide dismutase activities were increased, and the kidney reduced glutathione and urinary total antioxidant status were decreased (P<0.05). All of these changes were ameliorated by administration of Vit E, Vit C or especially the co-administration of both. In conclusion, HLP-induced hyperoxaluria reduced the kidney Klotho protein level, which could be restored by Vit E and/or Vit C.

Klotho protein contributes to cardioprotection during ischaemia/reperfusion injury

“…Interestingly, there are investigations demonstrating Klotho deficiency as a biomarker for kidney injury and for number of cancers, including breast cancer, lung cancer or hepatocellular carcinoma. They showed decrease in both plasma and urine Klotho protein levels in animal kidney injury models 34,39,44 . However, in our investigation, ischaemic heart injury and reduced mechanical function of the heart were related to the high content of Klotho in coronary effluents.…”

“…They showed decrease in both plasma and urine Klotho protein levels in animal kidney injury models. 34,39,44 However, in our investigation, ischaemic heart injury Research from the last few years showed protective effect of Klotho overexpression or administration during ischaemic injury of the brain and kidneys. 13,34 Thus, we studied if Klotho administration may mitigate I/R injury also in the cardiac cells.…”

“…It was shown that Klotho deficiency acts as an early biomarker for kidney damage and contributes to progression of chronic kidney disease. Thus, there is no renoprotection due to reduced expression of renal Klotho in the state of kidney disorders 36‐39 . Surprisingly, scientists have found depletion of renal Klotho level in the state of hypertension, diabetes and renal failure, but not after acute myocardial infarction in rats 40 .…”

“…Thus, there is no renoprotection due to reduced expression of renal Klotho in the state of kidney disorders. [36][37][38][39] Surprisingly, scientists have found depletion of renal Klotho level in the state of hypertension, diabetes and renal failure, but not after acute myocardial infarction in rats. 40 Furthermore, there was an association between higher serum Klotho level and reduced occurrence of cardiovascular events and cardiovascular death in human.…”

Inverse J-Shaped Relationship of Dietary Carbohydrate Intake with Serum Klotho in NHANES 2007–2016

“…We hypothesize that several mechanisms may underlie these observed relationships. Dietary carbohydrates themselves can serve as a source of certain vitamins [ 33 , 34 ], minerals [ 35 ], and fiber [ 27 ], which could positively influence Klotho protein expression. Additionally, low-carbohydrate-intake diets tend to inevitably reduce the intake of high-quality carbohydrates [ 28 , 36 ], including fruits, non-starchy vegetables, and whole grains, and simultaneously alter the amount and type of gut microbiota and affect hepatic FGF21 production [ 20 , 37 ], all of which may downregulate Klotho levels by modulating the levels of inflammation and oxidative stress.…”