Potentiation of mercury-induced nephrotoxicity by endotoxin in the Sprague-Dawley rat.
Endotoxin (lipopolysaccharide; LPS) and mercury are nephrotoxic compounds of food safety concern. Endotoxin is a product of cell walls of gram negative bacteria. Humans are constantly exposed to LPS through food, water and air. Food is the main source of mercury exposure for humans. Endotoxin potentiates the toxicity of a number of xenobiotics, but its interaction with nephrotoxic heavy metals has not been investigated. We tested the hypothesis that endotoxin enhances mercury-induced nephrotoxicity. Thirty-two, 41-43-day-old, male Sprague-Dawley rats were allocated randomly to four groups of eight rats each as follows: group I received 0.9% sodium chloride, group II received 2.0 mg of Escherichia coli 0128:B12 LPS kg(-1) once, group III received 0.5 mg mercuric chloride kg(-1) once, and group IV received 2.0 mg E. Coli 0128:B12 LPS kg(-1) once 4 h before receiving 0.5 mg mercury chloride kg(-1) once. Mercury, LPS and 0.9% sodium chloride were all injected IV through the tail vein. Rats were monitored for 48 h after mercury injection. Serum creatinine, urea nitrogen, and polyuria were significantly increased in rats given LPS plus mercury relative to those given either agent alone or saline (P</=0.05). The most severe morphologic lesions were found in rats given LPS plus mercury, which also had significantly greater renal mercury concentration than those given mercury alone (P < or = 0. 05). In conclusion, LPS potentiated mercury-induced nephrotoxicity.
Rumbeiha
W K
WK
Department of Veterinary Pathology, G303 Veterinary Medical Center, Michigan State University, East Lansing, MI 48824-1314, USA. rumbeiha@ahdlms.cvm.msu.edu
Fitzgerald
S D
SD
Braselton
W E
WE
Roth
R A
RA
Kaneene
J B
JB
D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004357:Drug Synergism; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli / Q000737:chemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008628:Mercury / Q000633:toxicity*; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D011141:Polyuria / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015431:Weight Loss / Q000187:drug effects
D004731:Endotoxins; D008070:Lipopolysaccharides; D003404:Creatinine; D008628:Mercury