Amelioration of Early Markers of Diabetic Nephropathy by Linagliptin in Fructose-Streptozotocin-Induced Type 2 Diabetic Rats

Mou

et al. 2022

Front. Mol. Biosci.

Renal fibrosis is a common feature of chronic kidney disease (CKD), and can lead to the destruction of normal renal structure and loss of kidney function. Little progress has been made in reversing fibrosis in recent years. Ferroptosis is more immunogenic than apoptosis due to the release and activation of damage-related molecular patterns (DAMPs) signals. In this paper, the relationship between renal fibrosis and ferroptosis was reviewed from the perspective of iron metabolism and lipid peroxidation, and some pharmaceuticals or chemicals associated with both ferroptosis and renal fibrosis were summarized. Other programmed cell death and ferroptosis in renal fibrosis were also firstly reviewed for comparison and further investigation.

Section: Ferroptosis Regulators and Renal Fibrosismentioning

confidence: 99%

Therapeutic Implications of Ferroptosis in Renal Fibrosis

Mou

et al. 2022

Front. Mol. Biosci.

“…Nakashima et al reported that linagliptin attenuates albuminuria in T1D rats by downregulating the AGE-RAGE axis independent of the glucose-lowering effects [87]. Linagliptin has been shown to inhibit tubular damage by attenuating oxidative stress, inflammation, and fibrosis in fructose-STZ (Fr-STZ)-induced diabetic rats, as proven by reductions in the levels of kidney injury molecule (KIM)-1 and neutrophil gelatinase-associated lipocalin (NGAL) [88]. Linagliptin has also been shown to attenuate albuminuria and kidney hypertrophy in a glucose-reduction-independent manner by upregulating renal antioxidants catalase and manganese superoxide dismutase (MnSOD) levels [89].…”

Section: Diabetic Animal Modelsmentioning

confidence: 99%

Renoprotective Effects of DPP-4 Inhibitors

et al. 2021

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Dipeptidyl peptidase (DPP)-4 inhibitors are widely used in the treatment of patients with type 2 diabetes (T2D). DPP-4 inhibitors reduce glucose levels by inhibiting degradation of incretins. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. It has been shown that an increased renal DPP-4 activity is associated with the development of DKD. A series of clinical and experimental studies showed that DPP-4 inhibitors have beneficial effects on DKD, independent of their glucose-lowering abilities, which are mediated by anti-fibrotic, anti-inflammatory, and anti-oxidative stress properties. In this review article, we highlight the current understanding of the clinical efficacy and the mechanisms underlying renoprotection by DPP-4 inhibitors under diabetic conditions.

“…According to a US Renal Data System report, 20-40% of diabetic patients in the United States display different degrees of renal injury, and DN is the first secondary factor leading to ESRD (3). The main clinical features of DN are proteinuria, progressive renal impairment and hypertension (4,5), and its prognosis and outcome are associated with a variety of mechanisms, such as hemodynamic changes, oxidative stress and inflammation. Therefore, research should be conducted to further understand the pathogenesis of DN, in order to develop novel therapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

Dendrobium mixture attenuates renal damage in rats with diabetic nephropathy by inhibiting the PI3K/Akt/mTOR pathway

et al. 2021

notable glomerular hypertrophy, an increase in mesangial matrix content and renal interstitial fibrosis. Moreover, DMix notably reduced kidney damage. The results demonstrated that DMix inhibited the phosphorylation of PI3K, Akt and mTOR in the kidney tissues of rats with DN, and increased the protein and mRNA expression levels of LC3 and Beclin-1. Therefore, it was suggested that DMix has protective effects on the kidney of rats with DN, which may be associated with the inhibition of the PI3K/Akt/mTOR signaling pathway and activation of renal autophagy by this traditional medicine.