Calcitriol Reduces the Inflammation, Endothelial Damage and Oxidative Stress in AKI Caused by Cisplatin

Abstract

Cisplatin treatment is one of the most commonly used treatments for patients with cancer. However, thirty percent of patients treated with cisplatin develop acute kidney injury (AKI). Several studies have demonstrated the effect of bioactive vitamin D or calcitriol on the inflammatory process and endothelial injury, essential events that contribute to changes in renal function and structure caused by cisplatin (CP). This study explored the effects of calcitriol administration on proximal tubular injury, oxidative stress, inflammation and vascular injury observed in CP-induced AKI. Male Wistar Hannover rats were pretreated with calcitriol (6 ng/day) or vehicle (0.9% NaCl). The treatment started two weeks before i.p. administration of CP or saline and was maintained for another five days after the injections. On the fifth day after the injections, urine, plasma and renal tissue samples were collected to evaluate renal function and structure. The animals of the CP group had increased plasma levels of creatinine and of fractional sodium excretion and decreased glomerular filtration rates. These changes were associated with intense tubular injury, endothelial damage, reductions in antioxidant enzymes and an inflammatory process observed in the renal outer medulla of the animals from this group. These changes were attenuated by treatment with calcitriol, which reduced the inflammation and increased the expression of vascular regeneration markers and antioxidant enzymes.

Effect of exogenous calcitriol on myopia development and axial length in guinea pigs with form deprivation myopia

“…Nevertheless, existing literature posits that vitamin D3 might modulate collagen I expression through its interaction with Transforming Growth Factor Beta(TGF-β) pathways, thus preventing the diminution of scleral collagen [27][28][29] . Recognized for its immunomodulatory and anti-inflammatory properties, calcitriol has been extensively applied in treating diverse conditions 12,30,31 . The link between inflammation and the development of myopia has recently received increasing attention, and many studies have shown that inflammation plays an important role in the occurrence and progression of myopia 32 .…”

“…It fulfills an indispensable role in facilitating the absorption of calcium within the small intestine and orchestrating the regulation of inorganic salt transport within the skeletal structure 11 . In the course of recent studys, calcitriol has been identified to exert substantial influence on cellular proliferation, differentiation, and the modulation of immune responses [12][13][14] . Calcitriol is currently being researched for its potential use in the treatment of diseases such as cancer 15 , heart disease 16 and periodontitis 17 .…”

Yishen Jiangzhuo decoction attenuates cisplatin‑induced acute kidney injury by inhibiting inflammation, oxidative stress and apoptosis through the TNF signal pathway

“…However, cisplatin easily accumulates and is biotransformed in the kidneys ( 2 ), which can lead to serious side effects including acute kidney injury (AKI). Of patients treated with cisplatin, ~30% develop AKI ( 3 ). This serious side effect limits the clinical application of cisplatin ( 4 ).…”