Although many investigators attempted to discover the reason for the lethal
effect of bithionol-s-oxide on lung flukes, there are only a few reports of its
effect on mitochondria.
The author present several interesting results noted following the oral
administration of bithionol-s-oxide to dogs which had been infected experimentally
with the metacercariae bithionol-s-oxide morphological changes in the adult worms
and in the cellular mitochondria were observed by light microscopy as well as by
Materials and Methods
There months after feeding the metacercariae of Paragonimus westermani, seven out
of 10 dogs were given oral doses of bithionol-s-oxide in the doses of 10mg., 20mg.,
30mg., 50mg., 70mg., 75mg., and 90mg. per kg. body weight respectively. The three
other dogs used as the control group. The size, shape and any changes in the adult
worms were observed. With the slides stained by the ordinary H and E stain method
and Heidenhain's iron hematoxylin method, general histological changes in the adult
worms were observed.
Mitochondira in the visceral organs of the adult worms were studied by light
microscopy, after adult worms were fixed in formalin, ferric chloride, Helly's
solution or Regaud's solution, and embedded in paraffin, sectioned, and stained by
Heidlenhains's iron hematoxylin method or Altmann-Kull method. The submicroscopic
detail of mitochondria was observed by HS-6 type electron microscope. the tissues
of the adult worm were fixed in 1% osmium tetroxide with pH 7.4 veronal-acetate
buffer, embedded in metacrylate, sliced at less than 0.1μ by the ultramicrtome,
Results and Conclusions
1. It was shown that the lethal dose of bithionol-s-oxide for the adult worms
ranged from 50 to 70 mg./kg. on the basis of study of the number, mobility and
morphological changes in the adult worms in both experimental and control groups.
2. While no differences were noted in histological findings between the
experimental groups (from 10 to 30 mg./kg.) and the control group, degenerative
changes such as cloudy swelling, hyaline degeneration and karyolysis were observed
with doses 50mg./kg. More severe degenerative changes were seen in the groups 70mg.
3. In both experimental and control groups, the shape of mitochondria in the
intestinal epithelia of the adult worms was generally round or elliptical. The
morphological changes of mitochondria reflecting the different dosages of
bithionol-s-oxide were as follows:
10mg./kg.……0.3μ in average diameter, similar to that of the control group.
20mg./kg.……Mitochondria wer swollen to 0.4-0.5μ.
30mg./kg.……Swollen further, then destructed or shrunken. Many irregular-sized
Mitochondria(0.1-0.6μ) were seen.
50mg./kg.……Mitochondria disappeared completely.
4. The mitochondria of the testicular and ovarian cells were generally fewer and
smaller than those of the intestianl epithelium, and the mitochondrial changes
varying with the different doses parallelled with those found in the intestianl
epithelium in the experimental group. The mitochondria of egg cells in the uterus
and reticulum cells were elliptical, round or rod in shape. There were significant
changes after bithionol-s-oxide administration.
5. The structural changes in mitochondria observed by electron microscopy after
bithionol-s-oxide administration were as follows:
10mg./kg.……The same as those of the control group.
20 and 30 mg./kg.……Swelling, thining, destruction, and disappearance of the
double membranes, degenerative, changes of the cristae such as irregular
arrangement, severance, destruction and vacuole formation. These were presumed to
be the result of destructive phenomena of the tricarboxylic acid cycle.