Lysophosphatidic Acid and Lovastatin Might Protect Kidney in Renal I/R Injury by Downregulating MCP-1 in Rat

Abstract

Renal ischemia/reperfusion (I/R) injury is a major cause of renal failure. The aim of our study is to explore the role of lysophosphatidic acid (LPA) and lovastatin on renal I/R injury and its mechanism in the rat. Male Wistar rats were randomly divided into sham-operated group; renal I/R for 0 h, 4 h, 12 h, and 24 h groups; LPA treatment group; and lovastatin treatment group (n = 10). Rats were killed to determine the level of monocyte chemotactic protein-1 (MCP-1) in renal tissue, renal function [serum creatinine (Cr) and blood urea nitrogen (BUN)], and renal histomorphology to evaluate the effectiveness of LPA and lovastatin. Normal renal tissue had a low level of MCP-1. The level of MCP-1 began to rise at 0 h after reperfusion, reached peak value at 4 h, and then gradually fell off. Compared with sham-operated group, MCP-1 was increased in all renal I/R injury groups (p < 0.01). With the extension of reperfusion, Cr and BUN were significantly increased (p < 0.01). There were damages in kidney tubules, renal interstitium, and kidney glomerulus in renal I/R injury groups. Paller's score was significantly increased in all renal I/R injury groups compared with sham-operated group (p < 0.01). LPA and lovastatin reduced the level of MCP-1, Cr, BUN, and damages of renal histomorphology (p < 0.01). The level of MCP-1 in renal tissue dynamically increases in renal I/R injury, indicating that MCP-1 is involved in renal I/R injury. LPA and lovastatin might protect renal function by downregulating MCP-1 in renal I/R injury.

Acute kidney injury in rats with or without pre‐existing chronic kidney disease: Cytokine/chemokine response

“…Similar findings were observed with plasma IL‐6 levels by Leelahavenichkul et al . in an alternative AKI model and others have reported increased levels of IL‐6 and MCP‐1 in kidney tissues after AKI induced by renal ischaemia and reperfusion (I/R) in rodents with normal kidney function prior to AKI. That model was fundamentally different from the one used in the current study, in which cytokine and chemokine responses within the kidney were equally increased (beside IL‐1β) in rats with CKD regardless of IIR exposure.…”

Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis

“…AA-treatment probably lowers the kidney levels of various LPLs that express differently homeostatic actions of the kidney integrity and functions. Gao et al [24] showed that intraperitoneal injection of LPA under ischemia was able to protect against the kidney injury due to ischemia/reperfusion.…”

Associations between plasma lysophospholipids concentrations, chronic kidney disease and the type of renal replacement therapy

“…Interestingly, LPA seems to be protective factor against the renal ischemia-reperfusion injury (I/R) which is important cause of acute renal failure in patients after renal transplantation, major surgical procedures or in hypovolemic shock [19, 20].…”