PMID- 35092082 OWN - NLM STAT- MEDLINE DCOM- 20220330 LR - 20220531 IS - 1099-0844 (Electronic) IS - 0263-6484 (Linking) VI - 40 IP - 2 DP - 2022 Mar TI - Vanillin attenuates thioacetamide-induced renal assault by direct and indirect mediation of the TGFbeta, ERK and Smad signalling pathways in rats. PG - 175-188 LID - 10.1002/cbf.3686 [doi] AB - 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 (TNFalpha), interleukin-6 (IL-6), extracellular signal regulated kinase 1/2 (Erk1/2), and transforming growth factor beta-1 (TGF-beta1) 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 alpha-smooth muscle actin (alpha-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 alpha-SMA renal expression and TNFalpha, IL-6, TGF-beta1, 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-beta type I receptors (ALK5) biding site. CI - (c) 2022 John Wiley & Sons Ltd. FAU - Metwaly, Heba A AU - Metwaly HA AUID- ORCID: 0000-0002-9593-4687 AD - Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. AD - Department of Biochemistry, Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - El-Eraky, Abdulrahman M AU - El-Eraky AM AD - Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - Ibrahim, Eman E AU - Ibrahim EE AD - Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - Kandil, Khaled K AU - Kandil KK AD - Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - El-Sayed, Mohamed A AU - El-Sayed MA AD - Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - El-Tabakh, Nayra M AU - El-Tabakh NM AD - Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - Motawea, Amr M AU - Motawea AM AD - Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - Ali, Helmi A AU - Ali HA AD - Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - Jabban, Maher Z AU - Jabban MZ AD - Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - Mahmoud, Mona E AU - Mahmoud ME AD - Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - Abdelfattah, Walaa H AU - Abdelfattah WH AD - Faculty of Pharmacy, Delta University, Gamasa, Egypt. FAU - Elmorsy, Mohammad A AU - Elmorsy MA AD - Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. FAU - Ghanim, Amal M H AU - Ghanim AMH AD - Department of Biochemistry, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt. LA - eng PT - Journal Article DEP - 20220129 PL - England TA - Cell Biochem Funct JT - Cell biochemistry and function JID - 8305874 RN - 0 (Benzaldehydes) RN - 0 (Smad Proteins) RN - 0 (Transforming Growth Factor beta1) RN - 075T165X8M (Thioacetamide) RN - CHI530446X (vanillin) SB - IM MH - Animals MH - *Benzaldehydes/pharmacology MH - Fibrosis MH - *Kidney/drug effects/metabolism/pathology MH - MAP Kinase Signaling System/drug effects MH - Molecular Docking Simulation MH - Rats MH - Signal Transduction/drug effects MH - *Smad Proteins/metabolism MH - *Thioacetamide/antagonists & inhibitors/toxicity MH - *Transforming Growth Factor beta1/metabolism OTO - NOTNLM OT - ALK5 OT - Erk1/2 OT - IL-6 OT - SMAD OT - TGF-beta1 OT - vanillin EDAT- 2022/01/30 06:00 MHDA- 2022/03/31 06:00 CRDT- 2022/01/29 05:47 PHST- 2021/10/18 00:00 [revised] PHST- 2021/08/29 00:00 [received] PHST- 2021/10/28 00:00 [accepted] PHST- 2022/01/30 06:00 [pubmed] PHST- 2022/03/31 06:00 [medline] PHST- 2022/01/29 05:47 [entrez] AID - 10.1002/cbf.3686 [doi] PST - ppublish SO - Cell Biochem Funct. 2022 Mar;40(2):175-188. doi: 10.1002/cbf.3686. Epub 2022 Jan 29.