• The Korean Journal of Pharmacology
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• v.7 no.1
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• pp.37-52
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• 1971

It has been demonstrated repeatedly that the administration of ethionine, a methionine analogue, will produce destruction of pancreatic tissue and liver cells. Destruction of acinar cells of pancreas by the administration of excess methionine similar to that seen after feeding diets supplemented with ethionine was also reported, but the liver was not involved by this amino acid. In an attempt to reproduce the results of these investigators the tissue damages were found to be slight and seen only irregulary in rats receiving ethionine on a complete diet and the result of tissue damages by excess methionine were also controversial. The present studies describe the toxicity of dietary supplemented ethionine and methionine to liver and pancreas in rats fed a low protein diet. Hundred five albino rats weighing around 120 gm were divided into three groups as follows; 1) Control group: A low protein diet containing 8% casein was fed throughout the experimental period. 2) Methionine group: A low protein diet (7% casein) supplemented with 1% methionine was used. 3) Ethionine group: A similar diet as methionine group except the supplementation of 1% ethionine instead of methionine was used. Five animals per wee from each group were killed for 6 weeks. The liver and pancreas were fixed in 10% formalin and histologic sections were prepared and stained with hematoxylin eosin. Serum amylase was expressed as much of glucose liberated from a starch substrate. The glucose was determined by the method of Nelson (1944). Serum glutamic pyruvic transaminase (SGPT) and glutamic oxaloacetic transaminase (SGOT) were determined by the technique described in Sigma Bulletin.

• Journal of Pharmacopuncture
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• v.17 no.3
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• pp.7-15
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• 2014

Objectives: The present study investigated the toxic properties of petroleum ether extract of Wattakaka (W.) volubilis in Wistar female rats. Methods: An in vitro brine shrimp lethality bioassay was studied in A. Salina nauplii, and the lethality concentrations were assessed for petroleum ether extract of W. volubilis. A water soluble portion of the test extract was used in different concentrations from $100-1000{\mu}g/mL$ of 1 mg/mL stock solution. A 24-hours incubation with a 1-mL aliquot in 50 mL of aerated sea water was considered to calculate the percentage rate of dead nauplii with test extract administration against a potassium-dichromate positive control. The acute and the sub-acute toxicities of petroleum ether extract of W. volubilis were evaluated orally by using gavage in female Wistar rats. Food and water intake, body weight, general behavioral changes and mortality of animals were noted. Toxicity or death was evaluated following the administration of petroleum ether extract for 28 consecutive days in the female rats. Serum biochemical parameters, such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, total cholesterol, triglyceride, total protein, glucose, urea, creatinine, sodium, potassium and ${\alpha}$-amylase levels, were measured in the toxicity evaluations. Pathological changes in isolated organs, such as the liver, kidneys, and pancreas, were also examined using hematoxylin and eosin dye fixation after the end of the test extract's administration. Results: The results of the brine-shrimp assay indicate that the evaluated concentrations of petroleum ether extract of W. volubilis were found to be non-toxic. In the acute and the sub-acute toxicity evaluations, no significant differences were observed between the control animals and the animals treated with extract of W. volubilis. No abnormal histological changes were observed in any of the animal groups treated with petroleum ether extract of W. volubilis. Conclusion: These results suggest that petroleum ether extract of W. volubilis has a non-toxic effect in Wistar female rats.

• Toxicological Research
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• v.31 no.4
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• pp.393-402
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• 2015

This study was conducted to measure toxicity of 1-chloropropane (CAS No. : 540-54-5). According to the OECD Test Guideline 413 (Subchronic inhalation toxicity: 90-day study), SD rats were exposed to 0, 310, 1,250, and 5,000 ppm of 1-chloropropane for 6 h/day, 5 day/week for 13 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, motor activity, ophthalmoscopy, hematology, serum chemistry, urinalysis, organ weights, gross and histopathological findings were compared between control and all tested groups. No mortality or remarkable clinical signs were examined during the study. No gross lesions or adverse effects on body weight, food consumption, motor activity, ophthalmoscopy, urinalysis, hematology, organ weights were observed in any of male or female rats in all tested groups. In serum biochemistry, glucose was significantly decreased in males of 1,250 and 5,000 ppm groups compared to control group in dose-dependent relationship. In histopathological examination, vacuolation of acinar cells was observed in pancreas of all male and female groups exposed to 1-chloropropane. In conclusion, no observable adverse effect level (NOAEL) was considered to be below 310 ppm/6 h/day, 5 day/week for rats.

• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.12-20
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• 1995

Clofibrate, a peroxisome proliferator, is hepatocarcinogenic in rats in a dose-dependent manner. A total of 70 male and female F344 rats, 5-week-old, were divided into three groups. Rats were fed clofibrate at 0, 0.25, or 0.5% in diet for 30 days. All rats were anesthetized with $CO_2$, blood samples were taken by cardiac puncture for hematology and clinical chemistry, and the rats were killed by exsanguination. Livers, kidenys, pancreas, adrenal glands, spleen, heart, lungs, thyroid gland, reproductive organs, and digestive organs were removed, weighed, later processed, and embedded with paraplast for histological examination. The relative liver and kidney weights with respect to final body weight in the clofibrate-treated group were significantly increased compared with those of control group at all dose levels (p<0.01). It has been suggested that clofibrate may influence on hepatotoxicity by increases in peroxisomal proliferation.

• Journal of Nutrition and Health
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• v.30 no.9
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• pp.1050-1054
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• 1997

In order to study the effects of green juice of Angelica keiskei Koidz on the toxicity of several selected elements, experiments were conducted with mice for a period of six weeks. The results obtained from the experiment are summarized as follows ; 1) Mice fed with 50 ppm of cadmium showed no adverse effects on the growth rate and mortality , but cadmium accumulation into the internal organs. 2) mice fed with 500ppm of lead showed no reduced effect on the growth rate and mortality, but lead accumulation was increased in the internal organs. The administration of green juice slightly reduced lead accumulation in the internal organs. 3) Mice fed with 50 ppm of selenium also showed no serious adverse effect of the growth rate and mortality , but selenium accumulation occurred in the internal organs. The administration of green juice slightly reduced selenium accumulation in the internal organs, but the modes and degrees of reduction in selenium accumulation were not consistent with the internal organs, liver, kidney and pancreas. 4) Mice fed with 500 ppm of chromium showed, numerically , an adverse effect on the growth rate, but showed no statistically significant difference. The administration of green juice rather increased the accumulation of chromium instead of reduction of chromium accumulation in the internal organs.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.31-36
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• 1981

Heavy metals which are present as trace elements in human body have been known to modify various enzymatic reaction. These metals can be essential or non-essential. Zinc, copper and calcium are essential in maintaining some biological processes, whereas non-essential metals such as cadmium, lead and mercury produce accumulatve toxic effect. Cadmium accumulated in pancreas can cause toxicity and damage of pancreatic cells, thereby influencing CHO metabolism. Lead compounds are known to produce toxic effects on the kidney, digestive system and brain fellowed by inhibition of activity of ${\rho}-aminolevulinic$ acid and biosynthesis of hemoproteins and cytochrome. Evidence has been accumulated that zinc not only acts as a cofactor in enzyme reaction but also prevents toxic effect induced by heavy metal such as copper and cadmium. To demonstrate the effect of heavy metals on pancreatic secretion, part of uncinate pancreas was taken and incubated in Krebs-Ringer bicarbonate buffer with heavy metals used. Additional treatment with CCK-OP was performed when needed. After incubation during different period of time, medium was analyzed for amylase activity using Bernfeld's method. The present study was attempted in order to elucidate the effect of several kinds of heavy metal on exocrine pancreatic secretion in vitro. The results obtained are as follows: 1) CCK-OP stimulated significantly amylase release from pancreatic fragments in vitro. 2) CCK-OP response of amylase release from pancreatic fragments was inhibited by treatmant with cadmium, especially high doses of cadmium. 3) CCK-OP response of amylase release from pancreatic fragments was inhibited when pretreated with $10^{-4}M$ copper chloride. 4) Lead chloride at the concentration of $10^{-3}M\;and\;10^{4}M$ stimulated the basal amylase release in vitro but CCK-OP response did not augment by lead chloride. 5) Zine chloride did not affect amylase release from pancreatic fragment in vitro. From the results mentioned above, it is suggested that CCK-OP response was inhibited it the amylase release from pancreatic fragments pretreated with cadmium and copper chloride.

• The Korean Journal of Pharmacology
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• v.11 no.1 s.17
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• pp.47-53
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• 1975

The metabolism of many drugs and also of steroid hormones is mediated by enzymes located in the microsomal fraction in smooth surfaced endoplasmic reticulum of mammalian liver. The duration and intensity of action of many drugs are largely determined by the speed at which they are metabolized in the body. Repeated administration of phenobarbital results in the induction of enzymes that metabolize a number of drugs. Lee et al. reported that daily administration of phenobarbital in rats significantly increased the activities of amylase in the pancreatobiliary juice, but the concentration of cholate in the bile was significantly lower in the treated group than that in the control group. After animals were treated with $CCl_4$, histological changes were shown in the endoplasmic reticulum, decreased microsomal enzyme activity and decreased hepatic protein synthesis were apparent. The purpose of the present report was to study the interaction between a 'microsomal-stimulating' agent such as phenobarbital and a 'microsomal- depressing' agent such as $CCl_4$ on hepatic and pancreatic functions in rats. The results obtained are summarized as follows: 1. The mortality rate of $CCl_4$ treated group was 34% and was decreased this figure to 15% with phenobarbital pretreatment. 2. In animals treated with phenobarbital the volume of biliary-pancreatic secretion was markedly elevated but the volume was decreased significantly in animals treated with $CCl_4$. 3. Total bilirubin output was elevated markedly in the $CCl_4$ treated group of rats pretreated with phenobarbital. The bilirubin concentration was increased in $CCl_4$ treated group and decreased in the group treated phenobarbital alone. 4. The concentration and total output of cholate in the bile were significantly lower in the all experimental group than control group. 5. In the animals treated with phenobarbital alone and phenobarbital plus $CCl_4$, the activity of lipase in pancreatobiliary juice was elevated, while in the animals treated with $CCl_4$ alone no change was observed. 6. The activity of amylase in the pancreatobiliary juice was decreased in the $CCl_4$ treated group, but elevated markedly in phenobarbital group and also elevated in phenobarbital-$CCl_4$ group. By the above results, it is concluded, when the liver was damaged by $CCl_4$, the exocrine function of pancreas and liver was decreased simultaneously. However, in the animals pretreated with phenobarbital, the toxicity of $CCl_4$ on the liver and pancreas was reduced.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.1
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• pp.134-142
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• 2010

Although BinSo-San(BSS), a mixed herbal formula consisted of 11 types of medicinal herbs and have been used as anti-inflammatory agent, In the present study, the acute toxicity (single oral dose toxicity) of lyophilized BSS aqueous extracts was monitored in male and female mice after oral administration according to Korea Food and Drug Administration (KFDA) Guidelines (2005-60, 2005). In order to observe the 50% lethal dose ($LD_{50}$), approximate lethal dosage (ALD), maximum tolerance dosage (MTD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (control) mg/kg (body wt.) according to the recommendation of KFDA Guidelines (2005-60, 2005). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines (2005-60, 2005) with organ weight and histopathology of 12 types of principle organs. We could not find any mortality, clinical signs and changes in the body weights except for dose-independent increases of body weight and gains restricted in 1000 mg/kg of BSS extracts-dosing female group. Hypertrophic changes of lymphoid organs.thymus, spleen and popliteal lymph nodes were detectedat postmortem observation with BSS extracts dose-dependent increases of lymphoid organ weights, and hyperplasia of lymphoid cells in these all three lymphoid organs at histopathological observations. These changes are considered as results of pharmacological effects of BSS extracts or their components, immunomodulating effects, not toxicological signs. In addition, some sporadic accidental findings such as congestion spots, cyst formation in kidney, atrophy of thymus and spleen with depletion of lymphoid cells, and edematous changes of uterus with desquamation of uterus mucosa as estrus cycles were detected throughout the whole experimental groups including both male and female vehicle controls. The significant (p<0.01) increases of absolute weights of kidney and pancreas detected in BSS extracts 1000 mg/kg-treated female group are considered as secondary changes from increases of body weights. The results obtained in this study suggest that the BSS extract is non-toxic in mice and is therefore likely to be safe for clinical use. The LD50 and ALD of BSS aqueous extracts in both female and male mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. In addition, the MTD of BSS extracts was also considered as over 2000 mg/kg because no BSS extracts-treatment related toxicological signs were detected at histopathological observation except for BSS or their component-related pharmacological effects, the immunomodulating effects detected in the present study.

• Journal of the Korean Society of Food Science and Nutrition
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• v.16 no.4
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• pp.262-267
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• 1987

The effect of Schizandrae fructus extract (S.F.E.) on experimentally alloxan-induced diabetes in rabbits and the acute toxicity on mice were studied; $LP_{50}$ of the extract was 21.50g/kg by intraperitoneal administration in mice. S.F.E. showed more rapid recovering effect than the control group : all samples showed excellent effect of lowering the hyperglycemia, that is, the blood glucose level was significantly decreased by 800mg/kg in 2 days and by 200mg/kg in 6 days. SGPT activity was lowered promptly after 4 days in 800mg/kg. Total cholesterol level was not shown significant lowering effect by 200mg/kg, but rapid by 800mg/kg in 6 days; blood urea nitrogen level was decreased gradually in 800mg/kg after 10 days and 14 days in 200mg/kg. In histological studies of pancreas, the sample groups exhibited less karyorrhexis, vacuolar and vesicular change, more stable in contents of ${\beta}-cells$ than the control group.

• Advances in Traditional Medicine
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• v.7 no.1
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• pp.94-99
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• 2007

The present study is aimed at finding the effect of B-20 drops, a homoeopathic formulation, in streptozotocin (STZ) induced diabetic rats. B-20 drops comprises of the constituents derived from plants and other natural sources, and are generally prescribed by the homoeopathic physician, in cases of hyperglycemia and diabetes. The elevated levels of fasting blood glucose and pancreatic lipid peroxides observed in rats treated with STZ were significantly reduced by the treatment of B-20 drops. The reduced liver glycogen contents were also brought back to near normal level by B-20 drops treatment in STZ diabetic rats. STZ induced histopathological changes in pancreas and liver was also partially reversed by B-20 drops. The findings indicate that B-20 drops help in improving the glycogen stores in the liver and prevents STZ induced damage through free radicals by decreasing the pancreatic lipid peroxides levels.