Chloroquine Attenuates Lithium-induced NDI and Proliferation of Renal Collecting Duct Cells.

Chloroquine Attenuates Lithium-induced NDI and Proliferation of Renal Collecting Duct Cells. Am J Physiol Renal Physiol. 2020 Apr 06;: Authors: Du Y, Qian Y, Tang X, Guo Y, Chen S, Jiang M, Yang B, Cao W, Huang S, Zhang A, Jia Z, Zhang Y Abstract Lithium is widely used in psychiatry as golden standard for more than 60 years due to its effectiveness. However, its adverse effect has been limiting its long-term use in clinic. About 40% patients taking lithium develop nephrogenic diabetes insipidus (NDI). Lithium can also induce proliferation of collecting duct cells, leading to microcysts formation in the kidney. Lithium was considered as autophagy inducer which may contribute to the therapeutic benefit of neuropsychiatric disorders. Thus, we hypothesized that autophagy may play a role in lithium induced kidney nephrotoxicity. To address our hypothesis, we fed mice with lithium-containing diet with chloroquine (CQ)-an autophagy inhibitor concurrently. Lithium-treated mice presented enhanced autophagy activity in kidney cortex and medulla. CQ treatment significantly ameliorated lithium-induced polyuria, polydipsia, natriuresis and kaliuresis accompanied with attenuated downregulation of AQP2 and NKCC2 protein. The protective effect of CQ on AQP2 protein abundance was confirmed in cultured cortical collecting duct cells. In addition, we found lithium-induced proliferation of collecting duct cells was also suppressed by CQ detected by PCNA...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research