Nephroprotective Effect of Adropinin Against Streptozotocin-Induced Diabetic Nephropathy in Rats: Inflammatory Mechanism and YAP/TAZ Factor

Abstract

Background

Diabetic Nephropathy remains a major cause of morbidity and mortality in patients suffering from renal dysfunction. This study accessed the nephroprotective role of Adropinin against streptozotocin (STZ) induced diabetic nephropathy in rats and scrutinizes the possible mechanism of action.

Methods

STZ (45 mg/kg) dose was used for inducing diabetic nephropathy (DN) and rats were divided into different groups and received the dose-dependent treatment of Adropinin. Blood glucose level, body weight, tissue weight, antioxidant, renal, hepatic parameters, and cytokines were determined. At the end of the experimental study, renal histopathology was performed.

Results

Adropinin significantly (P<0.001) boosted plasma insulin levels and reduced the blood glucose level. Adropinin considerably increased body weight and reduced kidney weight and kidney hypertrophy. Adropinin significantly (P<0.001) reduced urine outflow, microalbumin, total protein, blood urea nitrogen (BUN), uric acid and increased the creatinine, creatinine clearance. Adropinin significantly (P<0.001) reduced the indole sulfate level in the serum, kidney and reduced in the urine. Adropinin significantly (P<0.001) reduced the total cholesterol, triglyceride, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and increased the level of high-density lipoprotein (HDL). Adropinin significantly (P<0.001) increased the level of antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and reduced the level of malonaldehyde (MDA), 8-hydroxy-2ʹ -deoxyguanosine (8-OHdG). Adropinin significantly (P<0.001) reduced the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), transforming growth factor beta (TGF-β) and increased the level of interleukin-10 (IL-10), respectively. Adropinin treatment showed improvement in renal histopathology.

Conclusion

We can say that Adropinin showed the nephroprotective effect against the STZ-induced diabetic nephropathy rats via inflammatory and antioxidant pathway.

Keywords:

• nephropathy
• diabetes mellitus
• adropinin
• renal
• antioxidant
• inflammation

Abbreviations

STZ, streptozotocin; DN, diabetic nephropathy; IL-1β, interleukin-1β; IL-6, interleukin-6; TGF-β, transforming growth factor beta; IL-10, interleukin-10; DM, diabetes mellitus; AGEs, advanced glycation end products; ROS, reactive oxygen species; YAP, Yes-associated protein; Nrf2, nuclear factor erythroid-2 related factor-2; NF-κB, nuclear factor kappa B; IκB, inhibitor of κB; IKK, IκB kinase; iNOS, inducible nitric oxide synthase; COX-2, cyclooxygenase-2; TNF-α, tumor necrosis factor-α; Met, metformin; BUN, blood urea nitrogen; TC, total cholesterol; TG, triglyceride; HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very-low-density lipoprotein; GSH, glutathione; MDA, malonaldehyde; CAT, catalase; SOD, superoxide dismutase; 8-OHdG, 8-hydroxy-2ʹ-deoxy-guanosine.

Data Sharing Statement

The data that support the findings of this study are available on request from the corresponding author (Xiaoyan Xiao). The data are not publicly available due to [restrictions eg their containing information that could compromise the privacy of research participants].

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

The current research was funded by {Key R & D project of Shandong Province (Public welfare tackling of key scientific and technical problems), 2019GSF108111 role and mechanism of Yap / TAZ in diabetic nephropathy}.