Dencichine ameliorates renal injury by improving oxidative stress, apoptosis and fibrosis in diabetic rats.

Abstract

OBJECTIVE:

To investigate protective efficacies and mechanisms of dencichine on diabetic kidney injury via in vitro and in vivo assays.

METHODS:

Effects of dencichine on hydrogen peroxide (H2O2) induced oxidative damage in HK-2 renal cells were assessed by CCK-8 method. Forty streptozotocin (STZ)-induced diabetic rats with kidney injury were randomly divided into negative control group, three doses of dencichine (40, 80 and 160 mg/kg) groups. Blood biochemical and kidney related indexes as well adrenal morphological changes, apoptosis and autophagy related markers of diabetic rats were measured.

RESULTS:

Cell viability of HK-2 cells with oxidative damage induced by H2O2 was significantly improved by dencichine with 160 μg/mL for 43.7% and 320 μg/mL for 52.9% compared with control. Moreover, the decreased reactive oxygen species (ROS), and increased intracellular antioxidant enzymes including GPX1, SOD2 and GSH were showed in dencichine groups. In addition, incubation of dencichine in HK-2 cells promoted the increase of p-AMPK, BCL2, LC3, decreased activation of p-mTOR, BAX and Caspase 3. Chronic treatment of dencichine improved the STZ-induced diabetic characteristics of model rats. Further histopathological examination of renal tissues revealed 12-week treatment of dencichine effectively improved the morphology of nephropathy in diabetic rats. Moreover, dencichine also ameliorated excessive oxidation stress, down-regulated renal cell apoptosis and fibrosis related proteins, thereby protected renal tissues in diabetic rats.

CONCLUSION:

Dencichine ameliorated STZ-induced kidney injury mainly through inhibiting oxidative stress, reducing renal fibrosis, increasing autophagy, and reducing the renal cell apoptosis related proteins to protect nephrocytes and decrease renal tissue damage.

• Authors: Chao Huang, Lijing Cheng, Xinyan Feng, Xiaojun Li, Lihua Wang
• Journal: Life sciences (Life Sci) Vol. 258 Pg. 118146 (Oct 01 2020) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 32721462 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Amino Acids, Diamino
• Antioxidants
• oxalyldiaminopropionic acid

Topics

• Amino Acids, Diamino (therapeutic use)
• Animals
• Antioxidants (therapeutic use)
• Apoptosis (drug effects)
• Cell Line
• Diabetes Mellitus, Experimental (complications, drug therapy, metabolism, pathology)
• Diabetic Nephropathies (drug therapy, etiology, metabolism, pathology)
• Fibrosis
• Humans
• Kidney (drug effects, metabolism, pathology)
• Male
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley