PMID- 33964996 OWN - NLM STAT- MEDLINE DCOM- 20220103 LR - 20220103 IS - 0031-7144 (Print) IS - 0031-7144 (Linking) VI - 76 IP - 5 DP - 2021 May 1 TI - Anisodamine ameliorates ischemia/reperfusion-induced renal injury in rats through activation of the extracellular signal-regulated kinase (ERK) pathway and anti-apoptotic effect. PG - 220-224 LID - 10.1691/ph.2021.1302 [doi] AB - Anisodamine exerts significant protective effect on ischemia/reperfusion (I/R) injury in various organs. However, little is known about the mechanisms of anisodamine in renal I/R injury. Activation of extracellular regulated protein kinases (ERK) pathway promotes the repair of renal epithelial cells following oxidant injury. The present study investigated whether the renoprotective role of anisodamine against renal I/R injury in rats was associated with the activation of ERK signaling pathway. Male Sprague-Dawley (SD) rats were separated into the following groups: Sham-operated group, I/R group, anisodamine-treated group, PD98059 (MEK-1/ERK inhibitor)-treated group and anisodamine plus PD98059-treated group. A rat model of renal I/R was established by excising the right kidney and then clamping the left renal pedicle for 45 min followed by reperfusion for 24 h. Serum and renal tissue samples were obtained for assays of the associated morphological, molecular and biochemical parameters. Treatment with anisodamine ameliorated renal I/R injury, as evidenced by improvements of renal histology and kidney function, a decrease in paller's score and apoptosis index. Anisodamine also upregulated the phosphorylation levels of ERK1/2 and its downstream targets, including 90 ribosomal S6 kinase (p90rsk) and Bad, as well as the expression of antiapoptotic Bcl-2 protein, downregulated the expression levels of proapoptotic proteins Bax and cleaved-caspase-3, whereas these effects were greatly abolished by administration of PD98059. In conclusion, the results suggest that anisodamine prevents renal I/R injury in rats as a result of an activation of the ERK signaling pathway and anti-apoptotic properties. FAU - Zhang, Shu AU - Zhang S AD - Department of Pharmacology, Jiangsu, China. FAU - Xu, Xianzhi AU - Xu X AD - School of Stomatology, Xuzhou Medical University, Jiangsu, China. FAU - Huang, Yuanhong AU - Huang Y AD - School of Stomatology, Xuzhou Medical University, Jiangsu, China. FAU - Sun, Siyuan AU - Sun S AD - School of Stomatology, Xuzhou Medical University, Jiangsu, China. FAU - Jin, Chengqi AU - Jin C AD - School of Stomatology, Xuzhou Medical University, Jiangsu, China. FAU - Ji, Hao AU - Ji H AD - School of Stomatology, Xuzhou Medical University, Jiangsu, China. FAU - Sun, Dong AU - Sun D AD - Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Jiangsu, China;, Email: Sundong126@yahoo.com. FAU - Xia, Anzhou AU - Xia A AD - Department of Pharmacology, Jiangsu, China;, Email: xiaanzhou@xzhmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Pharmazie JT - Die Pharmazie JID - 9800766 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Flavonoids) RN - 0 (Solanaceous Alkaloids) RN - 01343Q8EL8 (anisodamine) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Acute Kidney Injury/*drug therapy/pathology MH - Animals MH - Apoptosis/*drug effects MH - Apoptosis Regulatory Proteins/metabolism MH - Epithelial Cells/drug effects MH - Flavonoids/pharmacology MH - Kidney/drug effects/metabolism MH - MAP Kinase Signaling System/*drug effects MH - Male MH - Models, Animal MH - Phosphorylation MH - Rats MH - Rats, Sprague-Dawley MH - Reperfusion Injury/*drug therapy/pathology MH - Signal Transduction/drug effects MH - Solanaceous Alkaloids/*pharmacology EDAT- 2021/05/10 06:00 MHDA- 2022/01/04 06:00 CRDT- 2021/05/09 20:24 PHST- 2021/05/09 20:24 [entrez] PHST- 2021/05/10 06:00 [pubmed] PHST- 2022/01/04 06:00 [medline] AID - 10.1691/ph.2021.1302 [doi] PST - ppublish SO - Pharmazie. 2021 May 1;76(5):220-224. doi: 10.1691/ph.2021.1302.