Comparison of toxic responses to acetaminophen challenge in ICR mice originating from different sources / 한국실험동물학회지

Acetaminophen (APAP) is the most common antipyretic analgesic worldwide. However, APAP overdose causes severe liver injury, especially centrilobular necrosis, in humans and experimental animals. At therapeutic dosage, APAP is mainly metabolized by sulfation and glucuronidation, and partly by cytochrome P450–mediated oxidation. However, APAP overdose results in production of excess reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), by cytochromes P450; NAPQI overwhelms the level of glutathione (GSH), which could otherwise detoxify it. NAPQI binds covalently to proteins, leading to cell death. A number of studies aimed at the prevention and treatment of APAP-induced toxicity are underway. Rats are more resistant than mice to APAP hepatotoxicity, and thus mouse models are mainly used. In the present study, we compared the toxic responses induced by APAP overdose in the liver of ICR mice obtained from three different sources and evaluated the usability of the Korl:ICR stock established by the National Institute of Food and Drug Safety Evaluation in Korea. Administration of APAP (300 mg/kg) by intraperitoneal injection into male ICR mice enhanced CYP2E1 protein expression and depleted hepatic GSH level 2 h after treatment accompanied with significantly increased level of hepatic malondialdehyde, a product of lipid peroxidation. Regardless of the source of the mice, hepatotoxicity, as evidenced by activity of serum alanine aminotransferase, increased from 8 h and peaked at 24 h after APAP treatment. In summary, hepatotoxicity was induced after the onset of oxidative stress by overdose of APAP, and the response was the same over time among mice of different origins.

Comparative study of liver injury induced by high-fat methionine- and choline-deficient diet in ICR mice originating from three different sources / 한국실험동물학회지

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. It is characterized by the accumulation of lipids without alcohol intake and often progresses to non-alcoholic steatohepatitis (NASH), liver fibrosis, and end-stage liver diseases such as cirrhosis or cancer. Although animal models have greatly contributed to the understanding of NAFLD, studies on the disease progression in humans are still limited. In this study, we used the recently reported high-fat L-methionine-defined and choline-deficient (HFMCD) diet to rapidly induce NASH and compared the responses to HFMCD in ICR mice from three different countries: Korea (supplied by the National Institute of Food and Drug Safety Evaluation), USA, and Japan during 6 weeks. Feeding HFMCD did not cause significant differences in weight gain in comparison with mice fed control diet. Relative weight of the liver increased gradually, while the relative weight of the kidneys remained unchanged. The parameters of liver injury (serum activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) increased rapidly from 1 week and remained elevated for as long as 6 weeks. Histopathological analysis showed that the accumulation of hepatic lipids induced by HFMCD was prominent at 1 week after diet supplementation and increased further at 6 weeks. Inflammatory markers were significantly increased in a time-dependent manner by HFMCD. The mRNA levels of TNF-α and IL-6 were elevated approximately 15-fold relative to control diet and that of IL-1β was increased more than 20-folds at 6 week after the onset of HFMCD intake. In addition, mRNA expression of fibrosis markers such as α-SMA, TGFβ1, and Col1a1 were also significantly increased at 6 week. In summary, the responses of Korl:ICR mice by intake of HFMCD diet were similar to those of ICR mice from other sources, which suggests that Korl:ICR mice is also a useful resource to study the pathogenesis of diet-induced NAFLD.

Comparative study of fatty liver induced by methionine and choline-deficiency in C57BL/6N mice originating from three different sources / 한국실험동물학회지

Non-alcoholic fatty liver disease (NAFLD) is believed to be the most prevalent liver disease worldwide and a major cause of chronic liver injury. It is characterized by lipid accumulation in the absence of significant alcohol consumption and frequently progresses to steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Although many studies have been conducted to better understand NAFLD since it was first recognized, there are still many gaps in knowledge of etiology, prognosis, prevention and treatment. Methionine-choline deficient (MCD) diet, a well-established experimental model of NAFLD in rodents, rapidly and efficiently produces the clinical pathologies including macrovesicular steatosis and leads to disease progression. In this study, we measured the response to MCD diet in C57BL/6N mice obtained from three different sources; Korea NIFDS, USA, and Japan. We evaluated changes in body weight, food consumption, and relative weights of tissues such as liver, kidney, gonadal white adipose tissue, inguinal white adipose tissue, and brown adipose tissue. These basic parameters of mice with an MCD diet were not significantly different among the sources of mice tested. After 3 weeks on an MCD diet, histopathological analyses showed that the MCD diet induced clear fat vacuoles involving most area of the acinus in the liver of all mice. It was accompanied by increased serum activities of alanine aminotransferase and aspartate aminotransferase, and decreased levels of serum triglyceride and cholesterol. In conclusion, the response of C57BL6N mice originating from different sources to the MCD diet showed no significant differences as measured by physiological, biochemical, and histopathological parameters.

Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources / 한국실험동물학회지

Doxorubicin is a widely used chemotherapeutic agents and is now part of standard therapeutic regimens for a variety of cancers (eg, hematopoietic malignancies and advanced solid tumors of the breast, ovary, thyroid, and bone). However, a potentially lethal and dose-dependent cardiotoxicity that appears within a short time after treatment limits the usage of doxorubicin in cancer patients. Although the mechanism of doxorubicin-induced cardiotoxicity is not completely understood, it is thought that free radical-induced oxidative stress and excessive production of reactive oxygen species are primary drivers of its toxicity. In this study, we compared the doxorubicin-induced cardiotoxicity of ICR mice obtained from three different sources and evaluated the utility of Korl:ICR stock established by the Korean FDA. Because doxorubicin-induced cardiotoxicity is thought to involve the excessive generation of ROS followed by oxidative stress, we determined the representative tissue index of oxidation, lipid peroxidation, and antioxidant, glutathione (GSH), as well as the parameters of heart injury. Doxorubicin treatment successfully induced cardiotoxicity as evidenced by histological examination and serum parameters (eg, levels of LDH and CK activities) in ICR mice. It was accompanied by increased lipid peroxidation and a decrease in both cysteine and GSH, further supporting previous reports that oxidative stress is a potential mechanism of doxorubicin-induced cardiotoxicity. Of interest, we did not observe a significant difference in doxorubicin-induced cardiotoxicity among mice of different origins. Collectively, our results suggest that Korl:ICR strain may be useful in the research of doxorubicin-induced cardiotoxicity.

Erratum: Comparative study of fatty liver induced by methionine and choline-deficiency in C57BL/6N mice originating from three different sources / 한국실험동물학회지

One of the authors' names was misprinted.

Erratum: Comparison of doxorubicin-induced cardiotoxicity in the ICR mice of different sources / 한국실험동물학회지

One of the authors' names was misprinted.

A Comparison of the Resting Energy Expenditure of Korean Adults Using Indirect Calorimetry / 대한지역사회영양학회지

The purpose of this study was to provide baseline data for revising the recommended energy intake for Korean adults. We recruited 290 adults so as to determine their resting energy expenditure (REE) and energy intake. The REE was measured by indirect calorimetry. We also calculated the REE from prediction equations formulated by World Health Organization (WHO). The energy intake for two consecutive days was assessed using the 24 hour recall method. The body weight, lean body mass (LBM) and percentage body fat were measured using the INBODY 3.0 system. We compared the results of three age groups; 20 to 29 years, 30 to 49 years and 50 years or more. The average energy intake of each age group was below the 7th Korean Recommended Dietary Allowances (RDA). The average energy intake was lower in the older age groups. However, no difference was observed among the age groups when the energy intake as a percentage of the Korean RDA was compared. Our measurement of the REE was higher than the REE calculated by the WHO's method. Correlation coefficients between the measured and the calculated values of REE for all age groups showed significant correlations (r = 0.475-0.672). As the ages of all the subjects increased, the REE/kg of body weight decreased. There were no significant differences in the REE / kg of the LBM between the different age groups; however, the REE/kg of the LBM was higher in the female group than in the male group. Negative correlations of the REE with the age (r = -0.242) and body fat ratio (r = -0.313) were observed; positive correlations of the REE with the BMI (r = 0.265), height (r = 0.570), weight (r = 0.562) and LBM (r = 0.586) were also found (p < 0.01).

The Development of a Simple Evaluation Questionnaire for Screening the Overweight-type Dietary Pattern in 30 to 49 Year Old Adults / 대한지역사회영양학회지

A study was performed to develop as a screening tool the Simple Evaluation Questionnaire for Screening the Overweight-type Dietary Pattern in 30 to 49 Year Old Adults. We used the data from the 30 to 49 year old subjects who participated in the three surveys - the health behavior survey, the dietary habit survey and the food intake survey - as the National Health and Nutrition Survey 1998. The 3,598 adults were classified into to two body fatness groups of normal (including underweight) and overweight (including obese) on the basis of their relative body weight (RBW). When comparing variables between the two groups, significant differences were found in gender, education, job, employment status, perceived health status, sadness / depression state, stress level, age, number of diseases, age when overweigh-tedness started, maximum body weight, sleep length, drinking pattern (yes / no), amount of alcoholic drinks, frequency of intoxication or drunkeness, amount of alcoholic drinks when drunk, intensity of exercise, frequency of exercise, exercise duration, skipped meals, small meals and drug supplements. In terms of food intake, there were significant differences in the daily food intake in terms of breakfast, dinner, daily kimchi and dairy products. In terms of mealtimes, we found differences in the amount of cooked rice at breakfast, kimchi at lunch, soup / kuk at dinner, fresh vegetables for snacks, fried foods for snacks between breakfast and lunch, and fruits / juices for snacks between lunch and dinner. After developing questions with indicators and analyzing the indicators by logistic regression analysis three times, we chose 10 questions for a simple evaluation of dietary patterns for the overweight-type category in order to give one point each. Among them we selected two questions to add one additional point and one question to add two additional points. The average scores of the overweight and normal groups, as shown by the developed questionnaire, were 5.97 +/-2.36 and 7.36 +/-2.21, respectively. A score of seven points was selected as the cut-off point. We examined the sensitivity, specificity and positive predictive value of the questionnaire to the results of 67%, 59% and 62%, respectively.