Vanillin attenuates thioacetamide‐induced renal assault by direct and indirect mediation of the TGFβ, ERK and Smad signalling pathways in rats

Abstract

Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Renal fibrosis is considered to be one of the most important conditions, as it may be the result of excessive extracellular matrix protein production and deposition, or prolonged exposure to nephrotoxic substances or drugs. Unfortunately, no suitable therapies or medications are currently available to prevent renal fibrosis. We conducted this study for the evaluation of the protective potential of vanillin by reversing TAA (250 mg/kg TAA for 6 weeks) induced renal injury in rats. The concentrations of the proteins tumour necrosis factor alpha (TNFα), interleukin‐6 (IL‐6), extracellular signal regulated kinase 1/2 (Erk1/2), and transforming growth factor beta‐1 (TGF‐β1) in kidney tissues were assessed using ELISA. Kidney Injury Molecule‐1 (KIM‐1) and mothers against decapentaplegic homologue 2, 3 (SMAD 2, 3) expressions were evaluated using real time PCR. We also estimated the expression of α‐smooth muscle actin (α‐SMA) using immunohistochemistry. Treatment with vanillin (100 mg/kg) significantly ameliorated kidney Injury and improved the kidney function. Vanillin treatment also significantly decreased the malondialdehyde (MDA) content, and elevated glutathione peroxidase (GPx) and catalase (CAT) activities in kidney tissues. Vanillin also reduced α‐SMA renal expression and TNFα, IL‐6, TGF‐β1, and Erk1/2 renal levels. Vanillin significantly decreased the expression of the genes encoding KIM‐1 and SMAD 2, 3 and ameliorated histological abnormalities in kidney architecture. Our molecular docking findings showed that vanillin has a good binding mode inside TGF‐β type I receptors (ALK5) biding site.

Mono‐ and bis‐edaravone adducts formed in the presence of vanillin in an aqueous solution

“…This work has pharmacological implications. The use of vanillin has been considered for the treatment of chronic kidney disease, to reduce oxidative damages, and ultimately to prevent renal fibrosis [26]. Vanillin is a tissue‐protective agent, capable of enhancing liver regeneration [27], protecting tissues from anticancer drug‐induced damages [28], and reducing metal‐induced lung inflammation [29].…”

Nrf2/HO‐1, NF‐κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats

“…Subsequently, blood samples were taken, and the serum was separated by spinning the samples in a centrifuge at 3000 rpm and 4°C for 5 min. The resulting serum was then stored at −80°C for future use in the analysis of biochemical parameters 29 …”

“…The resulting serum was then stored at −80°C for future use in the analysis of biochemical parameters. 29 …”

Erythropoietin mitigated thioacetamide-induced renal injury via JAK2/STAT5 and AMPK pathway

“…“Rats were fasted overnight at the end of the experiment, and then blood samples were collected, and the serum was obtained by centrifugation at 3000 rpm at 4°C for 5 min and stored at − 80°C, to be used later on for the measurements of blood urea and creatinine as kidney function tests” as described by 28 .…”

“…The second part was homogenized (100 mg of tissue: 1 mL of iced 0.5% potassium chloride) followed by 1-min sonication and 10 min centrifugation at 3000 rpm at 4°C, and finally, the supernatant was separated and preserved at − 80°C for the measurement of renal GSH and MDA using colorimetric “Bio-diagnostic® kits, Cairo, Egypt; Cat# MD 25 29, GR 25 11 and SD 25 21)” according to the method of Metwaly 28 . At the same time, the measurements of JAK2, STAT5, AMPK, and p-AMPK were assessed using enzyme-linked immunosorbent assay (ELISA).…”