• Journal of Pharmacopuncture
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• v.22 no.1
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• pp.35-40
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• 2019

Objective: Adriamycin (ADR) is an important anti-cancer drug which can cause renal toxicity. Given the known anti-inflammatory and antioxidant effects of Plantago major (P. major), the aim of this study was to determine the effects of hydroalcoholic extract of P. major on ADR- induced nephropathy in rats. Methods: Fifty male Wistar albino rats were randomly divided into 5 groups including: control, ADR (5 mg/kg), ADR + P. major (600 and 1200 mg/kg) and P. major (1200 mg/kg). The animals were treated with P. major extract for 5 consecutive weeks and ADR was intravenously injected on the 7th day of the study. Urine and serum samples were collected on days 0, 14, 21, 28, and 35 for the measurement of serum cholesterol and albumin levels and urine protein excretion rate. At the end of the study, the left kidneys were removed for apoptosis assessment. Results: Administration of ADR significantly decreased serum albumin level and increased serum cholesterol and urine protein excretion rate as well as, apoptotic cell numbers compared to the control group (P < 0.001) while had no effect on glomerular filtration rate (P > 0.05). Treatment with P. major, in both 600 and 1200 mg/kg doses, increased serum albumin level and decreased serum cholesterol concentration, urine protein excretion rate and as well as the number of apoptotic cell compared to the ADR group (P < 0.001). Conclusion: Our results showed that the P. major extract effectively protects against ADR- induced nephropathy by reducing kidney apoptosis and improving renal functioning in rats.

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.138-144
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• 1998

Purpose : The use of cyclosporine and mitomycin in various immunologic or neoplastic disorders has been known to cause wide-ranged nephrotoxic effects including thrombotic microangiopathy. However, the mechanism of nephrotoxicity of these drugs has not been studied adequately, so that present experimental study has been undertaken to find out whether these drugs can cause direct damage to the kidney and to clarify the pathogenetic mechanism of nephrotoxic effect of these drugs. Materials and methods : Sprague-Dawley rats weighing 250-300 gm were used for experimental animals and unilateral renal perfusion technique, modified from the method described by Hoyer et al was used. Isolation of left kidney from systemic circulation was made by clamping aorta and left renal vein and a hole was punctured in the anterior wall of the left renal vein. Cyclosporine (2.5 mg in 4 ml solution) and mitomycin (1.6 mg in 4ml solution) were infused through left renal artery and normal saline was used in control rats. Forty-eight hours after infusion of the drugs, animals were sacrificed and left kidney removed and processed for histologic examination. Total ischemic time of left kidney was less than 15 minutes: Results : Cyclosporine-perfused group showed severe swelling of glomerular endothelial ceil along with swelling of glomerular epithelial cell and interstitial vascular endothelial cell. Mitomycin-perfused group also showed severe swelling of glomerular endothelial and epithelial cells. And in addition to these findings, they demonstrated platelets aggregation, swelling and degranulation of platelets and fibrin accumulation in some of the capillaries, indicating occurrance of thrombotic microangiopathy. Conclusion : present experiment indicates that cyclosporine and mitomycin can cause direct toxic injury to renal endothelial cell. And this direct toxic damage to endothelial cell seems to be an important initiating event for the development of thrombotic microangiopathy.

• Applied Microscopy
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• v.39 no.4
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• pp.325-332
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• 2009

It has been well known that grapefruit seed extract (GSE) have effects on the deodorization and a wide range disinfectant. But anybody do not research about the decomposition-inhibition effect of GSE. The present study was performed to investigate the decomposition-inhibition effect of GSE by measuring the microscope and electroscope observation with passage of time. A total of 30 healthy Sprague-Dawley (SD) rats weighting from 230 gm to 250 gm were used as experimental animals. One group that do not treated by GSE named control group and the other group that treated by 55% GSE named Experimental group. Under ether anesthesia, right kidney was obtained. Put each sample in $37^{\circ}C$ and humidity $80{\pm}5%$ incubator, we obtained each sample after 0 day, 1 day, 2 days, 3 days, 4 days and 5 days. 4 ${\mu}m$ of paraffin sections were obtained, stained H-E stain and observed by use of a microscope. Morphological change in tissue was similar to control 1 day group and experimental 3 days group. Therefore, decomposition-inhibition effect of GSE continued about 2 days and it protected necrosis. According to above results, the author suggest that 55% GSE is an effective decomposition inhibitor until 2 days on $37^{\circ}C$ and humidity $80{\pm}5%$ conditions.

• Journal of Food Hygiene and Safety
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• v.16 no.4
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• pp.349-354
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• 2001

Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. We examined the antioxidative effect of sesamin and sesamolin on the preventing the development of insulin dependent diabetes mellitus using streptozotocin-induced Spraque Dawley diabetic rats. From 48 hours after injection of streptozotocin (60 mg/kg body weight), a portion of diabetic rats were fed with 0.2% sesamin and sesamolin containing diet for 3 weeks. There were significant differences of blood glucose and kidney weight between diabetic ports and control. Sesamin and sesamolin increased glutathione-S-transferase activity in kidney. The concentration of the thiobarbituric acid-reactive substances in the serum, liver, and kidney of diabetic rats administered sesamin and sesamolin decreased significantly as compared with that of the non-treated diabetic group. Dietary sesamin and sesamolin suppressed the oxidative stress in the diabetic rats. These results demonstrated that sesamin and sesamolin are potential and effective antioxidants that can protect the complications associated with diabetes.

• Toxicological Research
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• v.16 no.1
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• pp.47-52
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• 2000

To evaluate the renal toxicity of the antitumor agent, 1-(N-methyl) piperazinyl-3-phenyl-isoquinoline(CWJ-$\alpha$-5), rats were terated with CWJ-$\alpha$-5 (acute : 100mg/kg, i.p., single and subacute : 10mg/kr, i.p., daily for 7 days). The changes in the body weights, water consumption, kidney weights and urine volume after and during the treatment were observed. The concentrations of urinary creatinine, the activities of N-acetyl-$\beta$-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), $\gamma$-glutamyl transpeptidase ($\gamma$-GT) and lactate dehydrogenase (LDH) in 24 hr urine were also determined. The body weight and water consumption were decreased after the acute and subacute administration. However, the excretion of urine was not changed except the 1 day after the acute treatment. The excretion of creatinine was significantly decreased from 1 day after acute administration and continuously decreased. Also the excretion of creatinine was decreased during subacute administration. However, the protein excretion did not changed in both treatment. Those indicate that CWJ-$\alpha$-5 might decrease the metabolic rate of muscle. The urinary activities of NAG, AAP, $\gamma$-GT, and LDH were significantly affected by the drug treatment. The urinary activities of NAG, AAP and $\gamma$-GT were significantly increased 1 and 3 days after the acute administration and then returned to the control value. However, the urinary activities of LDH were increased 7 days after acute treatment. During subacute treatment, the urinary activities of $\gamma$-GT were not changed. However, the urinary activities of NAG, AAP and LDH were only significantly increased after the third administration. These results indicate that either the high acute dose or the subacute administration with low dose of the compound might induce a temporal damage in the kidney cells.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.102-113
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• 2006

Objectives & Methods : To obtain the 50% lethal dose(LD50), approximated lethal dose(ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study into such things as repeated dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male SD rats according to KFDA Guideline 1999-61[KFDA, 1999] at dosage levels of 2,000, 1,000, 500, 250 and 125 mg/kg/$10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. Results & Conclusions : After 2 or 3 days of dosing, 1 or 2 animals in 2,000 mg/kg-dosing groups died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and survivors recovered to normal within 3 or 4 days after dosing. Significant decrease in body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group, from 1 days after dosing compared to those of vehicle control group. Significantly diminished body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy and hemorrhage of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. The value for LD50 found in this study was 2,218.57 mg/kg. ALD in this study was 2,000 mg/kg, and the target organs are considered to be the heart and the kidney.

• Journal of Nutrition and Health
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• v.29 no.6
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• pp.578-589
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• 1996

This study was performed to invstigate the effect of dietary protein level and source on cadmium intoxicification in rats. Forty-eight male rats of Sprague-Dawley strain weighing 171$\pm$3g were blocked into 8 groups of 6 animals according to body weigth, and were raised for 30days. Eight experimental diets different with cadmium(0ppm, 400ppm)and protein(15%, 40%) levels and protein source[casien, I.S.P.(isolated soy protein)] were given to animals for 30days. Food intake, weight gain, food efficiency ratio, liver weight, kidney weight and femur weight were lower in cadmium added group, and higher in high protein groups(40% protein) than medium protein groups(15% protein). But, dietary protein source had no influence on them. Cadmium concerntration of liver was higher in rats fed casein than I.S.P. groups, and cadmium concentration in intestine was higher in high protein groups. In femur both high protein and I.S.P.diets increased cadmium concentrations. MT concdentrations in liver, kidney and intestine were higher in cadmium added group, and kidney intestine MT concentration were higher in high protein group. Absorption and retention rates of cadmium were lower in rat fed I.S.P. than animal fed casein among medium protein groups and cadmium concentration in blood and liver of I.S.P groups were lower than casein groups. But absorption and retention rates of cadmium were similar in high casein and I.S.P. groups. Renal damage by cadmium administration was not seen in all groups. Absorption rates of zinc and copper competing with cadmium in absorption process were lower in high protein groups than medium protein groups and lower in rats fed I.S.P. than casein. In conclusion, weight gain, F.E.R, and MT concentraion of high protein groups were higher than those of medium protein groups and absorption and retention rates of cadmium were lower in high protein groups. From these results, it was shown that cadmium toxicity was alleviated by high dietary protein. Meanwhile, the effect of dietary source on the cadmium toxicity was different with protein level. In medium protein groups absorption and retention rates of cadmium were much lower in rats fed I.S.P. than casein. In high protein groups, cadmium toxicity was not influenced by protein source and absorption and retention rates of cadmium were not different between casein and I.S.P. groups.

• Journal of Nutrition and Health
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• v.6 no.4
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• pp.15-22
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• 1973

Sodium chloride plays an important role as the main condiment at daily meal. It is well known that humans require sodium chloride as an essential nutrient to keep the homeostasis of electrolytes. The amounts of salt intake may be a reflection of geography, culture and food habit rather than necessity. Lee has reported (1962) that Koreans ingest high amounts of sodium chloride in their meals, with an intake of excess carbohydrate (80-90% of total Calories) and low protein in their diet. This includes large amounts of rice, Kimchi and other fermented soybean products common in the Korean diet. This investigation was designed to study the dietary relations of sodium chloride to other nutrients in the Korean diet. Twenty four albino male rats, weighing from 290-300g, were divided into four dietary groups according to the amounts of carbohydrate, protein and fat in the basal diet. Each diet contained a rice powder as a carbohydrate source. Diet I was a control diet, Diet II, low protein, Diet III, low protein and low fat diet and Diet IV, low fat diet. All rats were provided with 3% sodium chloride solution. Diet and salt solution were given ad libitum. The experiment was carried out for 9 weeks during which time the body weight, the food intake, and 3% sodium chloride solution consumption were determined. At the 9th week, the urine was collected the blood sample from the artery of each rat for the analysis of sodium and potassium and other chemical studies. The rats were sacrificed and the kidney, adrenal, liver and spleen were measured, and observed changes of the pathological tissue in the kidney and adrenal. The results were summarized as follows: 1) The growth rate was higher in Diet I than in the other experimental diets (II, III and IV) after 4 weeks. There was no significant difference found between the experimental Diets II, III and IV. 2) The daily food intake was greater in the experimental diets II, III and IV than in the control diet. However, there was no difference among the high carbohydrate diets Diet II, III and IV. 3) The daily water (3% sodium chloride solution) intake was also greater in the Diets II, III and IV, than in the control diet. However, there was no difference between Diets II, III and IV. 4) The concentration of sodium and potassium in the blood were within the normal range in all diets. 5) The amount of sodium chloride in the urine was significantly greater in Diets II, III and IV than in the control diet. Diets II, III, IV had a larger amount of sodium solution consumption. 6) Observation of pathological tissue in the experimental diets found a cell proliferation in the glomerlulus of the kidney, while such change was not found in the control diet.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1243-1252
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• 2002

To experiment the effects between cadmium inhalation toxicity and extracts of Folium Mori, rat inhalation exposure groups were exposed to cadmium aerosol in air by whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cadmium concentration in the air of cadmium aerosol was 1.02㎎/㎥ and mass median diameter(MMD) was 1.40μm. Intraperitoneal injection of extracts of Folium Mori to inhalation exposure groups was done for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were 126.39g/4 weeks and 19.18g/day from inhalation exposure group III, respectively. The highest lung and liver weight were 1.27g and 8.19g from inhalation exposure group II, respectively. The highest kidney weight was 1.805g from inhalation exposure control. The lowest cadmium content in lung was 86.39μg/g from inhalation exposure group III. The lowest cadmium concentration in blood was 7.12㎍/㎗ from inhalation exposure group III. Cadmium concentrations of 40.02㎍/g in liver and 69.18㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. For weekly cadmium concentration in urine, the value of the fourth week from inhalation exposure group III was the highest, 3.12㎍/㎖. For weekly cadmium concentration in feces, the value of the fourth week from inhalation exposure group III was the highest, 2.67 ㎍/g. The highest metallothionein concentration in lung was 74.65㎍/g from inhalation exposure group III and the highest metallothionein concentration in liver was 386.84㎍/g from inhalation exposure group II. The highest metallothionein concentration in kidney was 236.17 ㎍/g from inhalation exposure group II.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.700-710
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• 2003

For the experiment of the effects between cadmium aerosol inhalation toxicity and ethyl acetate extracts of Folium Mori, 4 inhalation exposure groups of rat were exposed to cadmium aerosol in air by whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cadmium concentration in the air was 0.96㎎/㎥ and mass median diameter (MMD) was 2.48㎛ with 1.85 of geometric standard deviation(GSD). Intraperitoneal injections of ethyl acetate extracts of Folium Mori to inhalation exposure groups were performed for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were 159.29/4 weeks in treated group III and 18.45g/day in treated group I, respectively. The highest lung and liver weights were 1.31 g in treated group I and 9.42g in treated group III, respectively. The highest kidney weight was 2.21g from treated group I. The lowest cadmium content in lung was 86.39㎍/g from treated group III and the lowest cadmium concentration in blood was 2.72㎍/㎗ from treated group II. Cadmium concentrations of 22.09㎍/g in liver and 24.82㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. For weekly cadmium concentration in urine, the value of the fourth week from treated group III was the highest, 1.35㎍/㎖. For weekly cadmium concentration in feces, the values of the second and fourth week from treated group I were the highest, 1.11㎍/g. The highest metallothionein concentration in lung was 31.85㎍/g from treated group III and the highest metallothionein concentration in liver was 205.77㎍/g from treated group III. The highest metallothionein concentration in kidney was 206.55㎍/g from treated group III. The highest Hct and Hb values were 38.26% and 11.63g/㎗ from treated group III, respectively. The highest RBC and WBC values were 7.68×106/㎣ and 9.85×10³/㎣ from treated group I, respectively.