Coenzyme q10 confers cardiovascular protection against acute mevinphos intoxication by ameliorating bioenergetic failure and hypoxia in the rostral ventrolateral medulla of the rat.
Coenzyme Q10 (CoQ10, ubiquinone) is a highly mobile electron carrier in the mitochondrial respiratory chain that also acts as an antioxidant. We evaluated the cardiovascular protective efficacy of CoQ10 at the rostral ventrolateral medulla (RVLM), a medullary site where sympathetic vasomotor tone originates and where the organophosphate poison mevinphos (Mev) acts to elicit cardiovascular intoxication. Experiments were carried out in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Microinjection bilaterally of Mev (10 nmol) into the RVLM induced progressive hypotension and minor bradycardia, alongside significant depression of the activity of NADH cytochrome c reductase (enzyme marker for Complexes I and III) or cytochrome c oxidase (enzyme marker for Complex IV) in the mitochondrial respiratory chain, reduction in ATP concentration, or tissue hypoxia in the RVLM. On the other hand, the activity of succinate cytochrome c reductase (enzyme marker for Complexes II and III) remained unaltered. The Mev-induced hypotension, bioenergetic failure, or hypoxia was significantly reversed when CoQ10 (4 microg) was coadministered bilaterally into the RVLM with the organophosphate poison. We conclude that CoQ10 confers cardiovascular protection against acute Mev intoxication by acting on the RVLM, whose neuronal activity is intimately related to the "life-and-death" process. We also showed that amelioration of the selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain, the reduced ATP level, and the induced tissue hypoxia in the RVLM are among some of the underlying mechanisms for the elicited protection.
Yen
David H T
DH
Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
Chan
Julie Y H
JY
Huang
C I
CI
Lee
C H
CH
Chan
Samuel H H
SH
Chang
Alice Y W
AY
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002319:Cardiovascular System; D003067:Coenzymes; D003576:Electron Transport Complex IV / Q000378:metabolism; D007022:Hypotension; D000860:Hypoxia; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000201:enzymology*; D008799:Mevinphos / Q000506:poisoning*; D008928:Mitochondria / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D000975:Antioxidants; D003067:Coenzymes; D014451:Ubiquinone; D008799:Mevinphos; D000255:Adenosine Triphosphate; D019802:Succinic Acid; D013384:Succinate Cytochrome c Oxidoreductase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; C024989:coenzyme Q10; D010100:Oxygen