Assessment of in vivo oxidative lipid metabolism following acute microcystin-LR-induced hepatotoxicity in rats.
Oxidative lipid metabolism as a result of acute cyanobacterial toxin-induced hepatotoxicity was monitored in male Sprague-Dawley rats using electron spin resonance (ESR) spectroscopy and image-guided proton nuclear magnetic resonance (1H-NMR) spectroscopy. ESR spectroscopy, coupled with spin trapping, was used to trap and detect lipid-derived radicals, formed in rat livers after acute in vivo exposure (LD50) to the cyanobacterial toxin, microcystin-LR (MCLR). A statistically significant increase in the levels (spectral peak integrals) of lipid radicals was detected in MCLR-treated livers (p < 0.05) (n = 8), in comparison to control livers (n = 6). In order to monitor lipid metabolism, before and for a period of 3 h, following toxin exposure, in vivo proton image-guided NMR spectroscopy was used. A statistically significant decrease in the levels of lipid methylene hydrogen resonances (spectral peak integrals) was observed from MCLR-treated livers (n = 6) 2 and 3 h post-exposure (p < 0.05), in comparison to controls (n = 6). Image-guided NMR spectroscopy was also used to detect significant decreasing levels of in vivo glutamine/glutamate, following exposure to MCLR. Biochemical assessment of perchloric extracts of liver glutamine and glutamate levels correlated with NMR spectroscopy results. Lactate levels measured as perchloric acid extracts, were also found to significantly decrease. In addition, assessment of serum enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were used to confirm hepatotoxicity (n = 20). This study strongly suggests that oxidative stress related processes are involved in in vivo microcystin-induced hepatotoxicity in mammals, and may play an integral role in MCLR-induced toxicity.
Towner
Rheal A
RA
Department of Physiology and Pharmacology, School of Biomedical Sciences, James Cook University, Townsville, Australia. rheal.towner@jcu.edu.au
Sturgeon
Sharelle A
SA
Hore
Kristin E
KE
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005973:Glutamine / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008387:Marine Toxins; D052998:Microcystins; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D005973:Glutamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C057862:cyanoginosin LR; D010100:Oxygen