Astragaloside II Ameliorated Podocyte Injury and Mitochondrial Dysfunction in Streptozotocin-Induced Diabetic Rats

Astragaloside II (AS II), a novel saponin purified from Astragalus membranes, has been reported to modulate the immune response, repair tissue injury, and prevent inflammatory response. However, the protective effects of AS II on podocyte injury in diabetic nephropathy (DN) have not been investigated yet. In this study, we aimed to investigate the beneficial effects of AS II on podocyte injury and mitochondrial dysfunction in DN. Diabetes was induced with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg in rats. Diabetic rats were randomly divided into four groups, namely, diabetic rats and diabetic rats treated with losartan (10 mg·kg−1·d−1) or AS II (3.2 and 6.4 mg·kg−1·d−1) for 9 weeks. Normal Sprague-Dawley rats were chosen as nondiabetic control group. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology and podocyte apoptosis, and morphological changes were evaluated. Expressions of mitochondrial dynamics-related and autophagy-related proteins, such as Mfn2, Fis1, P62, and LC3, as well as Nrf2, Keap1, PINK1, and Parkin, were examined by immunohistochemistry, western blot, and real-time PCR, respectively. Our results indicated that AS II ameliorated albuminuria, renal histopathology, and podocyte foot process effacement and podocyte apoptosis in diabetic rats. AS II also partially restored the renal expression of mitochondrial dynamics-related and autophagy-related proteins, including Mfn2, Fis1, P62, and LC3. AS II also increased the expression of PINK1 and Parkin associated with mitophagy in diabetic rats. Moreover, AS II facilitated antioxidative stress ability via increasing Nrf2 expression and decreasing Keap1 protein level. These results suggested that AS II ameliorated podocyte injury and mitochondrial dysfunction in diabetic rats partly through regulation of Nrf2 and PINK1 pathway. These important findings might provide an innovative therapeutic strategy for the treatment of DN.

Studi Subkronik.28 Hari: Uji Toksisitas Ekstrak Metanolik Kombinasi Scurulla atropurpurea dan Dendrophthoe pentandra terhadap Kerusakan Fungsi Ginjal Tikus Wistar Betina

Mistletoe tea (Scurrula. atropurpurea (Bl.) Dans) and Mistletoe Mango (Dendrophthoe pentandra) are parasitic plants that live on tea and mango plants, very potential as medicines, containing several secondary metabolite compounds such as flavonoids (quercetin). Flavonoids can act as natural antioxidants that can protect the kidneys from free radicals. Damage to kidney function can indicate from creatinine, BUN, urea, and renal histopathology. The.purpose.of.this study was.to determine toxicity of. a combination of. Mistletoe tea. extract and mango mistletoe (EMBTBM) to damage kidney function in female Wistar rats for 28 days, using the true experimental design method. Data on creatinine, bun, urea, and renal histopathology data were analyzed using the ANOVA. test. The number of test animals is 20 female white rats divided into four groups; each group there are five rats. Group.1 a control, then groups 3, and 4. as. treatment. Based on the results of the study showed that statistically significant. between. all groups. was p> 0.05. Therefore,.EMBTBM given to female.rats for.28 days at a dose.of 250 mg/KgBB, 500.mg/KgBB, and.1000 mg/KgBB reduces levels of creatinine, bun, urea and renal cell necrosis, in this case, the administration of EMBTBM tends to be safe and does not cause rise toxic properties in damage to kidney function in female Wistar rats. Keywords: .Subchronic, kidney function, and extract. ABSTRAK Benalu teh (Scurrula atropurpurea (Bl.) Dans) dan Benalu Mangga (Dendrophthoe pentandra) merupakan tanaman parasit yang hidup.menumpang pada tanaman teh dan mangga, sangat berpotensi sebagai obat-obatan, karena mengandung senyawa flavonoid yaitu quercetin dan rutin. Flavonoid berperan sebagai penyedia. antioksidan. alami. yang. melindungi. ginjal dari zat radikal.bebas. Kerusakan.fungsi ginjal diindikasi dari. kadar. kreatinin, BUN, urea, dan histopataologi ginjal. Tujuan penelitian ini adalah mengetahui. toksisitas pemberian. kombinasi ekstrak. benalu. teh. dan benalu mangga (EMBTBM) terhadap kerusakan fungsi ginjal pada tikus wistar betina selama 28 hari, dengan metode true eksperimental design. Data kadar kreatinin, bun, urea, dan histopatologi ginjal dianalisis menggunakan uji ANOVA. Penelitian ini menggunakan hewan.coba.berjumlah. 20. ekor. tikus. putih. betina. Hewan coba dibagi. menjadi 4.kelompok denga 5 ekor tikus pada tiap kelompok. Kelompok.1sebagai. kontrol, sementara kelompok. 3 dan 4 diberi perlakuan EMBTBM. Hasil. penelitian. menunjukan bahwa. perbedaan. nilai signifikan. antara. semua. kelompok. yaitu p>0.05..EMBTBM yang disondekan pada tikus wistar betina.selama 28.hari. dengan. dosis yang diberikan yaitu 250. mg/KgBB, 500. mg/KgB, dan 1000. mg/KgBB menurunkan kadar kreatinin, bun, urea dan nekrosis sel ginjal, dalam hal ini pemberian EMBTBM cenderung aman dan tidak menimbulkan sifat toksik pada kerusakan fungsi ginjal tikus wistar betina. Kata Kunci. : Ekstrak, Fungsi ginjal, dan Subkronik.

The Protective Impacts of Spriulina Platensis Against Cisplatin-Induced Renal Injury Through The Regulation of Oxidative Stress, Pro-Inflammatory Cytokines and Bax/Bcl2 Expression Cascade

One of the main antineoplastic chemotherapy medications is cisplatin; nephropathy is a major side effect of cisplatin. The current study investigates the molecular protective effect of Spirulina Platensis (SP) on cisplatin-induced nephrotoxicity. Forty eight healthy male albino rats were allocated into 4 groups. Group 1 received saline intraperitoneally (IP) twice per week (normal rats). Group 2, received SP (100 mg/kg bw orally). Group 3 injected cisplatin (1.5mg/kg IP) twice per week. Group 4 received SP and at 4th day received cisplatin (1.5mg/kg IP) for 21 days. After 3 weeks of experimentation, blood and renal tissues were taken for serum analysis, gene expression using qRT-PCR and renal histopathology. SP significantly ameliorated the alterations in the body weight, relative kidney weight, and the disturbance in examined renal markers. Furthermore oxidative stress biomarkers (MDA, NO, SOD, and GSH) induced by cisplatin were recovered and restored by SP. Cisplatin induced upregulation in the gene expression of TNF-α, iNOS, TGF1-β, IL-1β and IL-6 that were ameliorated by pre-administration of SP. Finally, cisplatin upregulated pro-apoptotic gene; Bax and downregulated anti-apoptotic gene; Bcl2. Of interest, SP mitigated this alteration in apoptosis and anti-apoptosis associated genes. Renal histopathology revealed the protective impacts of SP against cisplatin induced severe glomerular congestion, hemorrhage, inflammatory cell infiltration, degeneration and sever necrosis in renal glomeruli and tubules. In conclusion, SP has protective impact against cisplatin induced renal damage through the modulation of oxidative stress, anti-inflammatory, anti-necrotic and anti-apoptotic associated genes.