Mitochondrial damage was evident in the earliest lesions in cardiac muscle of rabbits poisoned by coffee senna (Cassia occidentalis), suggesting that mitochondria might be the target for the toxic action of coffee senna. Oxidative phosphorylation by mitochondria isolated from poisoned rabbits was uncoupled, and in more severely affected rabbits mitochondrial respiration was depressed. The activities of myocardial malic dehydrogenase, isocitric dehydrogenase and lactic dehydrogenase were increased, glycogen was depleted, and lactate accumulated in poisoned rabbits. The toxin(s) of coffee senna induced uncoupling of oxidative phosphorylation in myocardial mitochondria. Thus, the mitochondria, deprived of their ability to convert the energy derived from respiration into adenosine triphosphate, were unable to maintain ionic gradients and became swollen. This caused progressive failure of respiration with subsequent disruption of myocardial mitochondrial structure and myocardial degeneration.
References
1.
AmadorE.DorfmanL. E.WackerW. E. C.:
Serum lactic dehydrogenase activity. An analytical assessment of current assays.
Clin. Chem.9:
391–399
(1963).
2.
BlanchaerM. C.WrogemannK.:
Oxidative phosphorylation by mitochondria isolated from the hearts of Bio 14.6 myopathic hamsters.
Trans. N. Y. Acad. Sci., Series II30:
949–950
(1968).
3.
CarrollN. V.LongleyR. W.RoeJ. H.:
The determination of glycogen in liver and muscle by the anthrone reagent.
J. biol. Chem.220:
583–593
(1956).
4.
CassmanM.EnglardS.:
Beef heart malic dehydrogenases. V. A kinetic study of the reaction catalyzed by the supernatant enzyme.
J. biol. Chem.241:
793–799
(1966).
5.
ChanceB.WilliamsG. R.:
A simple and rapid assay of oxidative phosphorylation.
Nature, Lond.175:
1120–1121
(1955).
6.
ChanceB.WilliamsG. R.:
Respiratory enzymes in oxidative phosphorylation. III. The steady state.
J. biol. Chem.217:
409–427
(1955).
7.
ChappellJ. B.:
The oxidation of citrate, isocitrate and cis-aconitate by isolated mitochondria.
Biochem. J.90:
225–237
(1964).
8.
ChappellJ. B.GrevilleG. D.:
Effects of oligomycin on respiration and swelling of isolated liver mitochondria.
Nature, Lond.190:
502–504
(1961).
9.
ChenR. F.PlautG. W. E.:
Studies on the hydrogen transfer mediated by the DPN-linked isocitric dehydrogenase of heart.
Biochemistry2:
752–756
(1963).
10.
DelbruckA.ZebeE.BucherT.:
Über Verteilungsmuster von Enzymen des Energie liefernden Stoffwechsels im Flügelmuskel, Sprungmuskel und Fettkörper von Locusta migratoria und ihre cytologische Zuordnung.
Biochemistry331:
273–296
(1959).
11.
EnglardS.BreigerH. H.:
Beef heart malic dehydrogenases. II. Preparation and properties of supernatant malic dehydrogenase.
Biochim. biophys. Acta56:
571–583
(1962).
GreenD. E.AsaiJ.HarrisR. A.PennistonJ. T.:
Conformation basis of energy transformations in membrane systems. III. Configurational changes in the mitochondrial inner membrane induced by changes in functional states.
Arch. Biochem. Biophys.125:
684–705
(1968).
14.
HatefiY.YurtshukP.HaavikA. G.:
Studies on the electron transport system. XXXII. Respiratory control in beef heart mitochondria.
Arch. Biochem. Biophys.94:
148–155
(1961).
15.
HerdsonP. B.KaltenbachJ. P.JenningsR. B.:
Fine structure and biochemical changes in dog myocardium during autolysis.
Amer. J. Path.57:
539–558
(1969).
16.
JacobsonB. W.BlanchaerM. C.WrogemannK.:
Defective respiration and oxidative phosphorylation in muscle mitochondria of hamsters in the late stages of hereditary muscular dystrophy.
Canad. J. Biochem.48:
1037–1042
(1970).
17.
JenningsR. B.HerdsonP. B.SommersH. M.:
Structural and functional abnormalities in mitochondria isolated from ischemic dog myocardium.
Lab. Invest.20:
548–557
(1969).
18.
LardyH.JohnsonD.McMurrayW. C.:
Antibiotics as tools for metabolic studies. I. A survey of toxic antibodies in respiratory phosphorylative and glycolytic systems.
Arch. Biochem. Biophys.78:
587–597
(1958).
19.
LegatoM. J.SpiroD.LangerG. A.:
Ultrastructural alterations produced in mammalian myocardium by variation in perfusate ionic composition.
J. Cell Biol.37:
1–12
(1968).
LuftJ. H.:
Improvements in epoxy-resin embedding methods.
J. biophys. biochem. Cytol.9:
409–414
(1961).
23.
MercerH. D.NealF. C.HimesJ. A.EddsG. T.:
Cassia occidentalis toxicosic in cattle.
J. amer. vet. med. Ass.151:
735–741
(1967).
24.
MillionigG.:
Advantages of a phosphate buffer for OsO4 solutions in fixation.
J. appl. Physics32:
1637
(1961).
25.
MyersR. C.RemortelH.van:
The use of a reagent gel to locate LDH isoenzymes separated on cellulose acetate membranes.
Clin. Chem.14:
1131–1134
(1968).
26.
O'HaraP. J.:
Studies on the pathogenesis of the myopathy of coffee senna (Cassia occidentalis) poisoning in rabbits;
diss. College Station, Tex.
(1970).
27.
O'HaraP. J.PierceK. R.:
A toxic cardiomyopathy caused by Cassia occidentalis. I. Morphological studies in poisoned rabbits.
Vet. Path.11:
97–109
(1974).
28.
OlsonE.VignosP. J.jr.WoodcockJ.TaylorP.:
Oxidative phosphorylation in human muscular dystrophy.
J. Lab. clin. Med.71:
220–231
(1968).
29.
ReadW. K.PierceK. R.O'HaraP. J.:
Ultrastructural lesions of an acute toxic cardiomyopathy of cattle.
Lab. Invest.18:
227–231
(1968).
30.
RonaG.ChappelC. I.BalazT.GaudryR.:
An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat.
Arch. Path.67:
443–455
(1959).
31.
RosenbergJ. C.RushB. F.:
An enzymatic-spectrophotometric determination of pyruvic and lactic acid in blood. Methodologic aspects.
Clin. Chem.12:
299–307
(1966).
32.
ShawC. R.:
Isozymes: classification, frequency and significance.
Int. Rev. Cytol.25:
297–332
(1969).
33.
StonerC. D.ResselatM. M.SirakH. D.:
Oxidative phosphorylation in mitochondria isolated from chronically stressed dog hearts.
Circulat. Res.23:
87–97
(1968).
34.
Von KorffR. W.:
Metabolic characteristics of isolated rabbit heart mitochondria.
J. biol. Chem.240:
1351–1358
(1965).
35.
WeisslerA. H.KrugerF. A.BabaN.ScarpelliD. G.LeightonR. F.GallimoreJ. K.:
Role of anaerobic metabolism in the preservation of functional capacity and structure of anoxic myocardium.
J. clin. Invest.47:
403–416
(1968).
WestleyJ.LambethJ.:
Protein determination on the basis of copper binding capacity.
Biochim. biophys. Acta40:
364–366
(1960).
38.
WrogemannK.BlanchaerM. C.:
Oxidative phosphorylation by muscle mitochondria of dystrophic mice.
Canad. J. Biochem.45:
1271–1278
(1967).
39.
WrogemannK.BlanchaerM. C.JacobsonB. E.:
A magnesium-responsive defect of respiration and oxidative phosphorylation in skeletal muscle mitochondria of dystrophic hamsters.
Canad. J. Biochem.48:
1332–1338
(1970).
