• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10413-10420
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• 2015

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

• Biomedical Science Letters
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• v.4 no.2
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• pp.87-101
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• 1998

There is considerable interests in the effect of regular, vigorous exercise, in particular weight training as a possible measure in improving myocardial function. The present investigation aimed to examine possible effect of a long-term weight training program on the heart in aging rats. Male rats aged 3-,10-, and 20-month-old were divided at random into a control (sedentary) and the exercise group. The training group was exercised for 5 days a week by 1 RM of ten times with weight training apparatus. This investigation examined the changes of the heart muscle relative to histological, ultrastructural, cytochemical, and stereological studies in rats. Quantity of lipofuscin pigments was clearly increased in the weight training group of 15-month-old rats, and mitochondrial degeneration, vacuolization, and interstitial proliferation were observed as well. In the weight training group of 25-month-old rats the frequency as separated intercalated discs, fraying myofibrils and hypercontraction band increased in number compared with the same 15-mon1h-old group. From the experimental result of glucose-6-phosphatase activity, the enzyme activities decreased in the weight training group of 15-month-old rats, and more decreased in the same 25-month-old group. In stereological study, both 15- and 25-month-old training groups, mitochondrial and myofibrilar volume densities significantly decreased, whereas interstitial volume density significantly increased. From the experimental results obtained in the present study, it is suggested that long-term weight training exercise do not cause any significantly qualitative and quantitative ultrastructural change of the heart muscle in the young. On the contrary, long-term weight training exercise stress may actually induce degenerative changes in the heart muscle in the old age.

• Applied Microscopy
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• v.32 no.1
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• pp.1-8
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• 2002

To confirm the effect of electroacupuncture on the regeneration of injured peripheral nerve, the change of evoked potential in the sciatic nerve, the change of enzyme activity in the spinal cord, and morphological change of injured sciatic nerve were examined comparatively in acupuncture group (AG) and control group (CG) after sciatic nerve of guinea pig was injured by purpose. The value of evoked potential after injury of the sciatic nerve was increased in both AG and CG, but the increase rate of that was higher in AG than CG. Acid phosphatase activity of the spinal cord was increased in 1CG and 2AG, but shown are tendency to return to the normal state as time went by. Ultrastructural recovering rate of the injured sciatic nerve was higher in AG than CG. Also, there was developed only adipose tissue in sciatic nerve of AG. As mentioned above, the effect of electroacupuncture on the regeneration of injured peripheral nerve was confirmed experimentally by change of evoked potential, acid phosphatase and ultrastructure. Especially, the effect of electroacupuncture was appeared clearly in an early stage than other treatment stages.

• Korean Journal of Veterinary Research
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• v.30 no.1
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• pp.85-91
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• 1990

This study was designed in order to investigate the effect of copper sulfate to the ultrastructural changes of the hepatocytes in Sprague Dawley rats. The animals were administered with copper sulfate (10mg/kg B.W.), which was dissolved in normal saline. The solution was injected into abdominal cavity every day. The animals were sacrificed at the 6th, 12th, and 24th day from the beginning of administration. The specimens obtained from the liver were observed with electron microscope and significant changes were as follows. 1. A prominent dilatation and disruption of the cisternae of rough endoplasmic reticulum were recognized. Also, the detachment of membrane bound ribosomes was shown. 2. The proliferation of smooth endoplasmic reticulum and the depletion of glycogen particles were noted. 3. The increase of primary lysosomes and autophagic vacuoles was obserbed. 4. The dilatation of mitochondrial cristae was obserbed. And it was irregulary scattered in the stroma of mitochondria. 5. The atrophy of microvilli in the bile canaliculi and space of Disse was prominent. 6. Membrane of hepatocytes was damaged and significant hydrophic degeneration was obserbed in the perisinusoidal regions. 7. The damage of Fat-storing cells was more significant than that of hepatocytes.

• Applied Microscopy
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• v.17 no.2
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• pp.55-71
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• 1987

To investigate the effects of lead on the electron transport system and ultrastructure of mouse kidney mitochondria, various lead acetate concentrations were treated in vitro and respiration rate, enzyme activities were measured. Ultrastructural changes at state IV respiration were also observed. To compare with in vivo experiments, mouse were injected intraperitoneally of 100 mg lead acetate per kg body weight and state IV respiration rate and enzyme activities were measured. Ultrastructure of renal proximal tubular cells were also observed. In in vitro treatement, decreased state IV respiration, decreased enzyme activities, ruptured membranes and inhibition of condensed to orthodox transformation were observed. In in vivo treatment, decreased state IV respiration and decreased enzyme activities were observed after 24 hrs of i.p. injection. Cytochrome c oxidase activity showed twice the inhibition compared to NADH-CoQ reductase activity at 24 hrs. Continuous decreased state IV respiration was observed after 48 and 72 hrs of injection, however, the enzyme activities were increased to control level. Lead-protein complex which probably inhibits the toxic effects of lead appeared. To conclude, dominant effect of lead on the electron transport system appeared at cytochrome c oxidase activity, and the increased enzyme activities may be a result of appearance of lead-protein complex.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2753-2758
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• 2012

Rubia cordifolia Linn, which belongs to the Rubiaceae family, is a well-known herb used in Ayurvedic medicine. In the present study, we investigated the influence of a methanolic extract (RC) on the induction of apoptosis in HEp-2 (human laryngeal carcinoma) cell line, as evidenced by cytotoxicity, morphological changes and modification in the levels of pro-oxidants. Inhibition of cell proliferation and lactate dehydrogenase (LDH) release increased in a time and dose-dependent manner. Further, reduced glutathione (GSH), glutathione transferase (GST) and protein levels decreased and lipid peroxidation increased significantly on RC treatment in a dose dependent manner when compared to controls. Based on the results we determined the optimal dose as 30mg/ ml and the apoptotic effect of RC extract (30 mg/ml) on HEp-2 cells was confirmed by fluorescent microscopy and transmission electron microscopy (TEM) based on morphological and ultrastructural changes. RC extract suppressed the proliferation of HEp-2 oral cancer cells inducing apoptotic cell death in vitro. These results point to potential of RC extract as an agent for the treatment of laryngeal squamous cell carcinoma.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.13 no.1
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• pp.17-27
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• 1983

The author observed the effects of /sup 60/Co irradiation on the development and subcellular structure of tongue tissue of the fetal rats. The lower left abdomen of mothers were exposed to radiation on 15½th day of gestation with 300R. The fetuses were removed on the 6hr, 14hr, 24hr, 48hr and 72hr after irradiation and the light microscopic and electron microscopic observations of the lingual epithelium, lamina propria and muscle layer were carried out. The results were as follows: 1. The irradiated fetuses showed the retardation of filiform papillae formation. 2. Epithelial cells revealed fusion and myelination of mitochondria, large autolysosomes, increased lipid droplets, retardation of tonofilaments and desmosome formation. 3. In the lamina propria, undifferentiated cells showed bleb formation of nuclear membrane, pyknosis and fragmentation of nucleus, edema of cytoplasm I and nucleus, increased auto-lysosomes, dilatation of cell membrane and cell necrosis. Also, collagenous fibril formation was inhibited by irradiation. 4. In the muscle layer, growth of myotubes was inhibited. Myotubes showed swelling of mitochondria, loss of mitochondrial cristae, autolysosomes, retardation of myofibril formation, and large vacuoles. Undifferentiated cells adjacent myotube contained pyknotic nucleus and autolysosomes. 5. Among the various tissues of tongue, it seems that mesenchymal cells were most radiosensitive.

• Applied Microscopy
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• v.17 no.1
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• pp.29-46
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• 1987

To study hexavalent chromium effects on mitochondrial electron transport, the activities of electron transport enzymes and conformational change of mitochondria treated with $40{\mu}M$ of sodium dichromate ($Na_{2}Cr_{2}O_{7}\;2H_{2}O$) were investigated. And so were those of liver mitochondria isolated from mouse intraperitoneally injected with sodium dichromate, 40mg per kg body weight. On both treatment with chromium(VI), the activities of electron transfer enzymes (Complex I and IV) were increased to some extent and the ultrastructural transformation of mitochondria from a condensed to an orthodox conformation was inhibited under State IV respiration. These results represent' inhibitory effect of hexavalent chromium on electron transport without inhibiting electron transfer enzymes (Complex I and IV) in mitochondria. On intraperitoneal treatment with hexavalent chromium as sodium dichromate and trivalent chromium as chromic chloride, containing 37.5 mg of chromium per kg body weight, respectively, the activities of electron transfer enzymes of liver isolated from mouse with chromium(VI) was reduced, but that with chromium(III) was not affected. And with chromium(VI), all mice after 12 hours of treatment died, only after 6 hours survived. With chromium(III), however, all survived. This indicates that hexavalent chromium is more toxic than trivalent chromiumin mouse liver.

• The Journal of Korean Physical Therapy
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• v.16 no.2
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• pp.63-71
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• 2004

Denervated skeletal muscle produces muscle atrophy as well as changes at the neuromuscular junction which leads to terminal axonal sprouting and an ultrastructural remodeling. NT-3 is expressed in adult muscle and motoneurons. Normally NT-3 has a potential role in regulating adult neuromuscular jungtion and recovering following muscle atrophy. Also, it could influence synaptic neurotransmission between motoneurons and skeletal muscle cells. The purpose of this study was to investigate the effect of electrical stimulation therapy(EST) on NT-3 expression in neuromuscular junction following sciatic nerve transsection in rats. After EST application during 7 days, the immunoreactivity of NT-3 was increased in neuromuscular junction

• Korean Journal of Veterinary Pathology
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• v.3 no.1
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• pp.7-14
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• 1999

We investigated the effect of a single intravenous dose of Fumonisin $B_1(FB_1$) of rat kidney on the time sequence. Male Sprague-Dawley rats were intravenouslyin jected with FB$_1$at 1.25 mg/kg and were euthanized at 12 hrs, 1, 2, 4, and 6 days after the injection. In $FB_1$ treated rats, serum BUN and creatinine were elevated from 12 hrs. Microscopically, the initial target site was tubules of inner stripe, with mild degenerative and necrotic changes at 12 hrs, but the tubules recovered on day 4. In outer stripe, there were only a few scattered necrotic cells on day 1. These changes became more obvious over the time passed and most severe on day 4. On day 6, regeneration occurred, manifest as hypertrophic, basophilic tubular cells. The dying cells were proved to necrotic cells instead of apoptotic cells by TUNEL. Ultrastructural changes were cytoplasmic vacuole, dilated endoplasmic reticulum, swollen mitochondria, ballooned microvilli of the tubular cell in the outer stripe. These results showed that the renal tubules of outer medulla were the target to $FB_1$-induced nephrotoxicity in the rat. However, initial target was mner stnpe of medulla.