Renal-protective effect of thalidomide in streptozotocin-induced diabetic rats through anti-inflammatory pathway

Abstract

BackgroundDiabetic nephropathy (DN) is a major microvascular complication in diabetes. An increasing body of evidence has shown that DN is related to chronic inflammation, kidney hypertrophy, and fibrosis. While thalidomide has been shown to have anti-inflammatory and antifibrotic effects, the effects of thalidomide on the pathogenesis of DN are unclear. This study was undertaken to explore whether thalidomide has renal-protective effects in diabetic rats.MethodsMale Sprague Dawley rats were injected intraperitoneally with 50 mg/kg streptozotocin to induce diabetes. Diabetic rats were treated with thalidomide (200 mg/kg/d) for 8 weeks, and then blood and urine were collected for measurement of renal function-related parameters. Histopathology, immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot analyses were performed to assess renal proinflammatory cytokines, fibrotic protein, and related signaling pathways.ResultsDiabetic rats exhibited obvious renal structural and functional abnormalities, as well as renal inflammation and fibrosis. Compared with diabetic control rats, those treated with thalidomide showed significantly improved histological alterations and biomarkers of renal function, as well as reduced expression of renal inflammatory cytokines, including NF-κB and MCP-1. Furthermore, renal fibrotic proteins, such as TGF-β1, TβRII, TβRI, smad3, collagen IV, and fibronectin were also remarkably suppressed. Treatment with thalidomide markedly stimulated the phosphorylation of AMPKα.ConclusionIn this study, thalidomide suppressed the inflammatory and fibrotic processes in DN. These effects were partly mediated by the activation of AMPKα, and inhibition of the NF-κB/MCP-1 and TGF-β1/Smad signaling pathways. These results suggest that thalidomide may have therapeutic potential in diabetic renal injury through the anti-inflammatory pathway.

Effect of a polyherbal formulation in streptozotocin-induced diabetic nephropathy in wistar rats

“…[16] Hence, we tried to explore the renoprotective effect of an in-house polyherbal churna formulated with herbs which has been proved to possess antidiabetic, antioxidant, anti-inflammatory, and antifibrotic activities. [17] From the literature, it is very clear that lipid/lipoprotein abnormalities are a commonly observed status in type-II DM that are risk factors for renal atherosclerosis formation and further affect the renal blood flow. [18] Pretreatment of DN rats with PHF at doses 250 and 500 mg/kg bw remarkably decreased the TG, TC, VLDL, and LDL and improved the HDL levels dose dependently, and it was clearly witnessed from the existence of known medicinal herbs with antihyperlipidemic active principles of polyherbal churna ( Gymnema sylvestre – gymnemic acids, gymnemasaponins).…”

Thalidomide decreases high glucose‑induced extracellular matrix protein synthesis in mesangial cells via the AMPK pathway

“…Previous studies have demonstrated the anti-inflammatory effects of Thd in diabetic retinopathy, neuropathy and cardiomyopathy animal models (20)(21)(22). A previous study demonstrated the renal-protective effect of Thd in DN rats through the activation of AMPK and inhibition of NF-κB/MCP-1 and TGF-β1/mothers against decapentaplegic homolog (Smad) signaling pathways (23). The association between Thd-induced AMPK activation and the inhibition of HG-induced MC proliferation and ECM accumulation via NF-κB and TGF-β1 signaling remains unknown.…”

Protective Effects of Thalidomide on High-Glucose-Induced Podocyte Injury through In Vitro Modulation of Macrophage M1/M2 Differentiation

“…Our preliminary work on streptozotocin-induced rats showed that Tha suppressed the inflammatory and fibrotic processes in diabetic renal injury [ 8 ]. These effects were partly mediated by the activation of AMPK α and inhibition of the NF- κ B/MCP-1 and TGF- β 1/Smad signaling pathways [ 7 ].…”