Augmentation of mercury-induced nephrotoxicity by endotoxin in the mouse.
Endotoxin (lipopolysaccharide; LPS) and mercury are compounds of food safety concern. Endotoxin is a product of cell walls of gram negative bacteria. Humans are constantly exposed to LPS through infection plus translocation into circulation from the gastrointestinal tract. Food is the major source of mercury in humans. The toxic interaction between LPS and mercury has not been well investigated. In a previous study, we demonstrated that LPS potentiated mercury-induced nephrotoxicity in the rat. Whether this observation was species specific was not clear. In this study we tested the hypothesis that LPS enhances mercuric chloride (HgCl(2))-induced nephrotoxicity in mice. In a 2x2 factorial design, mice received either Escherichia coli 0128:B12 endotoxin (2.0 mg/kg body weight) or 200 microliter of 0.9% sodium chloride (saline), and this was followed 4 h later by either mercury (1.75 mg mercuric chloride per kg body weight) or 200 microliter of saline. Mice were monitored for 48 h. Monitored end-points included body and renal weights, urine volume, renal histology and ultrastructural pathology, serum urea nitrogen and creatinine, selected serum and urine cytokines, and renal mercury concentrations. Endotoxin by itself was not nephrotoxic at the dose used in this study. Overall, mice given LPS plus mercury were the most severely affected. Mice given LPS and mercury also had significantly greater renal mercury concentration than those given mercury alone (P</=0.05). In conclusion, LPS potentiates mercury-induced nephrotoxicity in the mouse.
Rumbeiha
W K
WK
Department of Veterinary Pathology, National Food Safety and Toxicology Centre, G303 Veterinary Medical Center, Michigan State University, 48824-1314, East Lansing, MI, USA. rumbeiha@msu.edu
Fitzgerald
S D
SD
Braselton
W E
WE
Roth
R A
RA
Pestka
J J
JJ
Kaneene
J B
JB
D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008627:Mercuric Chloride / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008809:Mice, Inbred C3H; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D008627:Mercuric Chloride; C044101:endotoxin, Escherichia coli; D003404:Creatinine