Efficacy and local irritation evaluation of Eriobotrya japonica leaf ethanol extract / 한국실험동물학회지

BACKGROUND: Although Eriobotrya japonica leaves have been studied as a raw material for various cosmetic products, little is known about the anti-oxidant, anti-inflammatory, and anti-melanogenic activities of Eriobotrya japonica leaf ethanol extract (EJEE). METHODS: This study was conducted to evaluate the anti-oxidant, anti-inflammatory, and anti-melanogenic activities of EJEE using different in vitro models. In addition, we investigated the potential irritation of EJEE to skin and eye using animal alternative tests. RESULTS: The total content of polyphenols, one of the active constituents of EJEE, was analyzed by high-performance liquid chromatography and found to contain 88.68 mg tannic acid equivalent/g. EJEE showed a concentration-dependent 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging activity, and a superoxide dismutase-like activity. The anti-inflammatory effect of 0.5% (w/v) EJEE was demonstrated by a reduction in lipopolysaccharide-induced nitric oxide and tumor necrosis factor-alpha levels in RAW 264.7 cells. EJEE also significantly inhibited melanogenesis in melanocyte stimulating hormone-induced B16F1 cells. EJEE did not show any irritation in skin and eye in animal alternative test. CONCLUSIONS: These results indicate that the EJEE possesses anti-oxidant, anti-inflammatory, and anti-melanogenic activities, while it did not induce toxicity or irritation in neither skin nor eye. Therefore, EJEE can be used as a cosmetic ingredient for skin improvement.

Chronic Treatment with Combined Chemotherapeutic Agents Affects Hippocampal Micromorphometry and Function in Mice, Independently of Neuroinflammation

Chemotherapeutic agents induce long-term side effects, including cognitive impairment and mood disorders, particularly in breast cancer survivors who have undergone chemotherapy. However, the precise mechanisms underpinning chemotherapy-induced hippocampal dysfunction remain unknown. In this study, we investigated the detrimental effects of chronic treatment with a combination of adriamycin and cyclophosphamide (AC) on the neuronal architecture and functions of the hippocampi of female C57BL/6 mice. After chronic AC administration, mice showed memory impairment (measured using a novel object recognition memory task) and depression-like behavior (measured using the tail suspension test and forced swim test). According to Golgi staining, chronic AC treatment significantly reduced the total dendritic length, ramification, and complexity as well as spine density and maturation in hippocampal neurons in a sub-region-specific manner. Additionally, the AC combination significantly reduced adult neurogenesis, the extent of the vascular network, and the levels of hippocampal angiogenesis-related factors. However, chronic AC treatment did not increase the levels of inflammation-related signals (microglial or astrocytic distribution, or the levels of pro-inflammatory cytokines or M1/M2 macrophage markers). Thus, chronic AC treatment changed the neuronal architecture of the adult hippocampus, possibly by reducing neurogenesis and the extent of the vasculature, independently of neuroinflammation. Such detrimental changes in micromorphometric parameters may explain the hippocampal dysfunction observed after cancer chemotherapy.

Protective effect of water extract of guibi-tang against pulmonary inflammation induced by cigarette smoke and lipopolysaccharide / 한국실험동물학회지

Water extract of guibi-tang (GB), a traditional Chinese, Japanese, and Korean herbal medicine, is used to treat memory impairment, insomnia, and peptic ulcers. The aim of this study was to investigate the protective effects of GB on pulmonary inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). C57BL/6 mice were used to develop a pulmonary inflammation model by exposing them to CS for 1 h per day for 7 days. LPS was intranasally administered to mice under mild anesthesia on day 5. GB was administered 1 h before CS exposure at doses of 50 or 100 mg/kg for 7 days. Our results showed that GB suppressed the CS and LPS induced elevation in inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), with significant reductions in protein, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels. Histological studies revealed that GB decreased the inflammatory cell infiltration into lung tissue caused by CS- and LPS-exposure. GB also significantly decreased the CS and LPS-induced expression of inducible nitric oxide synthase (iNOS) in the lung tissue. Taken together, GB effectively attenuated airway inflammation caused by CS and LPS. These results indicate that GB is a potential therapeutic herbal formula for pulmonary inflammatory disease.

Inhibitory effects of Pycnogenol®, a pine bark extract, in a rat model of testosterone propionate-induced benign prostatic hyperplasia / 한국실험동물학회지

Benign prostate hyperplasia (BPH) is a male reproductive disease that has gained increasing importance in recent years. The present study investigated whether Pycnogenol® (PYC), a standardized French maritime pine bark extract, could prevent BPH induced by testosterone propionate (TP) in rats. Male Sprague-Dawley rats were randomly divided into five groups of six rats. One group was used as a normal control rats and the other groups received subcutaneous injections of TP for 4 weeks to induce BPH. In the two treatment groups, PYC (20 or 40 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the induction of TP. All rats were sacrificed at the scheduled termination time, the prostates were weighed, and histopathologic examinations were conducted. Dihydrotestosterone (DHT) levels in serum and the prostate were measured, and the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 proteins was investigated. BPH-treated animals showed increases in the relative weight of the prostate, higher concentrations of DHT in serum and the prostate, and higher expression of PCNA and Ki-67 in the prostate; in contrast, PYC-treated animals had significant reductions in these factors compared with the BPH animals. These findings indicated that PYC inhibited the development of BPH and that this was closely associated with a reduction in DHT concentration.

Probiotic properties and adsorption of Enterococcus faecalis PSCT3-7 to vermiculite

The probiotic properties of Enterococcus (E.) faecalis PSCT3-7, a new strain isolated from the intestines of pigs fed dietary fiber containing 50% sawdust, were investigated. E. faecalis PSCT3-7 tolerated a pH range of 3 to 8 and 0.3% bile salts, and it inhibited the growth of Salmonella Typhimurium in a concentration-dependent manner. In addition, E. faecalis showed resistance to several antibacterial agents. Vermiculite, a nutrient and microbial carrier, increased the bile tolerance of the strain. Scanning electron microscope images revealed good adsorption of E. faecalis PSCT3-7 onto vermiculite. E. faecalis PSCT3-7 represents a potential probiotic candidate to administer with vermiculite to swine.

Pine bark extract (Pycnogenol®) suppresses cigarette smoke-induced fibrotic response via transforming growth factor-β1/Smad family member 2/3 signaling / 한국실험동물학회지

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of Pycnogenol® (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth factor-β1 (TGF-β1) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in TGF-β1/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.

Artemisia argyi attenuates airway inflammation in lipopolysaccharide induced acute lung injury model / 한국실험동물학회지

Artemisia argyi is used as a health supplement, tea, and food source in Korea. This study aimed to evaluate the effect of Artemisia argyi (AA) and its active compound, dehydromatricarin A (DA), on the attenuation of airway inflammation in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). The C57BL/6 mice were administered AA (50 mg/kg or 100 mg/kg) and DA (10 mg/kg or 20 mg/kg) by oral gavage from day 0 to 7 days and LPS treated by intranasal instillation 48 hours before the sacrifice. The treatment of AA and DA markedly decreased inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared with that in ALI-induced mice, which was accompanied by a significant reduction in the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BALF. Furthermore, the administration of AA and DA clearly decreased inducible nitric oxide synthase (iNOS) expression and nuclear factor kappa B (NF-κB) phosphorylation in comparison with that in the ALI-induced mice. The histological examination of the lung tissue revealed that the administration of AA and DA suppressed the inflammatory cell infiltration into the peribronchial and alveolar lesions induced by LPS instillation. Collectively, our results indicated that AA and DA effectively decreased the airway inflammatory response induced by LPS instillation. Therefore, AA and DA may offer a potential therapy for airway inflammatory disease.

HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette smoke and lipopolysaccharide / 한국실험동물학회지

HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-α, interleukin (IL)-6 and IL-1β in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD.

Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury / 한국실험동물학회지

In this study, the potential hepatotoxicity of 1,3-dichloro-2-propanol and its hepatotoxic mechanisms in rats was investigated. The test chemical was administered orally to male rats at 0, 27.5, 55, and 110 mg/kg body weight. 1,3-Dichloro-2-propanol administration caused acute hepatotoxicity, as evidenced by an increase in serum aminotransferases, total cholesterol, and total bilirubin levels and a decrease in serum glucose concentration in a dose-dependent manner with corresponding histopathological changes in the hepatic tissues. The significant increase in malondialdehyde content and the significant decrease in glutathione content and antioxidant enzyme activities indicated that 1,3-dichloro-2-propanol-induced hepatic damage was mediated through oxidative stress, which caused a dose-dependent increase of hepatocellular apoptotic changes in the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and immunohistochemical analysis for caspase-3. The phosphorylation of mitogen-activated protein kinases caused by 1,3-dichloro-2-propanol possibly involved in hepatocellular apoptotic changes in rat liver. Furthermore, 1,3-dichloro-2-propanol induced an inflammatory response through activation of nuclear factor-kappa B signaling that coincided with the induction of pro-inflammatory mediators or cytokines in a dose-dependent manner. Taken together, these results demonstrate that hepatotoxicity may be related to oxidative stress-mediated activation of mitogen-activated protein kinases and nuclear factor-kappa B-mediated inflammatory response.

Acute toxicity and cytotoxicity evaluation of Dendrobium moniliforme aqueous extract in vivo and in vitro / 한국실험동물학회지

Dendrobium moniliforme (L.) Sw., an herb of the Orchidaceae family, has long been used in traditional medicine to strengthen bones, nourish the stomach, and promote the production of bodily fluid. Recently, polysaccharides isolated from Dendrobium have been used in functional foods and nutraceutical products. A traditional method to process Dendrobium is to soak fresh stems in an ethanol solution, which is the most important factor to ensure high yields of aqueous-extractable polysaccharides. The present study was carried out to investigate the potential acute toxicity of D. moniliforme aqueous extract (DMAE), by a single oral dose in Sprague-Dawley rats. The test article was orally administered once by gavage to male and female rats at doses of 0, 2,500, and 5,000 mg/kg body weight (n=5 male and female rats for each dose). Throughout the study period, no treatment-related deaths were observed and no adverse effects were noted in clinical signs, body weight, food consumption, serum biochemistry, organ weight, or gross findings at any dose tested. The results show that a single oral administration of DMAE did not induce any toxic effects at a dose below 5,000 mg/kg in rats, and the minimal lethal dose was considered to be over 5,000 mg/kg body weight for both sexes. With respect to cytotoxicity, the cell viability of human embryonic kidney (HEK293) cells was less than 50% when the cells were treated with 10 mg/mL aqueous extract for 24 h.

Diallyl disulfide attenuates acetaminophen-induced renal injury in rats / 한국실험동물학회지

This study investigated the protective effects of diallyl disulfide (DADS) against acetaminophen (AAP)-induced acute renal injury in male rats. We also investigated the effects of DADS on kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), which are novel biomarkers of nephrotoxicity in renal tissues, in response to AAP treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) AAP (1,000 mg/kg), (3) AAP&DADS, and (4) DADS (50 mg/kg/day). AAP treatment caused acute kidney injury evidenced by increased serum blood urea nitrogen (BUN) levels and histopathological alterations. Additionally, Western blot and immunohistochemistry analysis showed increased expression of KIM-1 and NGAL proteins in renal tissues of AAP-treated rats. In contrast, DADS pretreatment significantly attenuated the AAP-induced nephrotoxic effects, including serum BUN level and expression of KIM-1 and NGAL proteins. Histopathological studies confirmed the renoprotective effect of DADS. The results suggest that DADS prevents AAP-induced acute nephrotoxicity, and that KIM-1 and NGAL may be useful biomarkers for the detection and monitoring of acute kidney injury associated with AAP exposure.

Evaluation of 2-week repeated oral dose toxicity of 100 nm zinc oxide nanoparticles in rats / 한국실험동물학회지

The aim of this study was to verify subacute oral dose toxicity of positively charged 100 nm zinc oxide (ZnO(AE100[+])) nanoparticles (NPs) in Sprague-Dawley rats. ZnO(AE100[+]) NPs were administered to rats of each sex by gavage at 0, 500, 1,000, and 2,000 mg/kg/day for 14 days. During the study period, clinical signs, mortality, body weight, food consumption, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. Increased mortality and clinical signs, decreased body weight, feed consumption, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet (PT), and lymphocyte (LYM) and increased white blood cells (WBCs), neutrophils (NEUs), alkaline phosphatase (ALP), and histopathological alterations in the spleen, stomach, and pancreas were observed at 2,000 mg/kg/day. Increased clinical signs, decreased body weight, feed consumption, HB, HCT, MCV, MCH, MCHC, and LYM and increased WBCs, NEUs, ALP, and histopathological alterations in the spleen, stomach, and pancreas were seen at 1,000 mg/kg/day. Increased clinical signs, decreased MCV and MCH and increased histopathological alterations in the stomach and pancreas were found at 500 mg/kg/day. These results suggest that the target organs were the spleen, stomach, and pancreas in rats. The no-observed-adverse-effect level was <500 mg/kg for both sexes.

Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-kappaB Pathways

This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-kappaB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-alpha), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-kappaB, COX-2, iNOS, TNF-alpha, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-kappaB, COX-2, iNOS, TNF-alpha, p-JNK, and p-ERK. These results indicate that DADS prevents CP-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF-kappaB and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.

Effect of probiotic 379D as an alternative to antibiotics for feed supplementation in broiler chickens / 동물의과학연구지

Antibiotics have been used to prevent disease, promote growth rate, and improve feed efficiency. However, the use of antibiotics in livestock has been restricted worldwide due to problems such as bacterial resistance. Therefore, probiotics among alternatives to antibiotics have gained attention in the livestock feed industry these days. This study was conducted to investigate the effects of dietary supplementation with probiotic 379D on safety, growth rate, and feed efficiency. In this study, bacterial strain 379D was isolated from soil and identified as a Bacillus sp. according to 16S rRNA sequence analysis. In an in vitro test, in-gel activity assay and antimicrobial susceptibility test were conducted to evaluate 379D. In an in vivo study, 379D was administered at concentrations of 0.1% and 1% to broiler chickens for 28 days. The results of in-gel activity assay and antimicrobial susceptibility test showed that strain 379D had broad spectrum antimicrobial activity. Furthermore, no adverse 379D-related effects were observed in 0.1% and 1% groups. Feed efficiency was higher in the 379D-treated groups than in the control group. In conclusion, 379D is expected to be used as a safe alternative to antibiotics in a feed supplement and will improve feed efficiency in broiler chickens.

Protective effects of pine bark extract against cisplatin-induced hepatotoxicity and oxidative stress in rats / 한국실험동물학회지

We investigated the protective effects of pine bark extract (pycnogenol(R), PYC) against cisplatin-induced hepatotoxicity and oxidative stress in rats. Twenty-four male rats were divided into the following four groups: (1) vehicle control, (2) cisplatin (7.5 mg/kg), (3) cisplatin & PYC 10 (10 mg/kg/day), and (4) cisplatin & PYC 20 (20 mg/kg/day). A single intraperitoneal injection of cisplatin induced hepatotoxicity, as evidenced by an increase in serum aminotransferase and histopathological alterations, including degeneration/necrosis of hepatocytes, vacuolation, and sinusoidal dilation. In addition, an increase in the malondialdehyde (MDA) concentration and a decrease in the reduced glutathione (GSH) content and catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) activities were observed in the cisplatin-treated rat hepatic tissues. In contrast, PYC treatment effectively prevented cisplatin-induced hepatotoxicity, including the elevation of aminotransferase and histopathological lesions, in a dosedependent manner. Moreover, PYC treatment also induced antioxidant activity by decreasing MDA level and increasing GSH content and SOD and GST activities in liver tissues. These results indicate that PYC has a protective effect against acute hepatotoxicity induced by cisplatin in rats, and that the protective effects of PYC may be due to inhibiting lipid peroxidation and increasing antioxidant activity.

Green tea ameliorates recognition memory defects in acute radiation syndrome caused by gamma irradiation / 동물의과학연구지

An evidence suggests that even low-dose irradiation can lead to progressive cognitive decline as well as memory deficits in both humans and experimental animals in part due to hippocampal dysfunction. To determine whether or not green tea (GT) and epigallocatechin gallate (EGCG) could attenuate memory impairment as well as suppress hippocampal neurogenesis, passive avoidance and object recognition memory test as well as TUNEL assay and immunohistochemical detection with markers of neurogenesis (Ki-67 and doublecortin (DCX)) were performed using adult mice treated with relatively low-dose gamma irradiation (2.0 Gy). GT was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hr preirradiation and at 30 minutes post-irradiation, or orally at a dosage of 250 mg/kg of body weight/day for 7 days before autopsy. EGCG (25 mg/kg of body weight) was administered intraperitonially at 36 and 12 hr pre-irradiation and at 30 minutes post-irradiation. In the passive avoidance and object recognition memory test, mice trained for 1 day after acute irradiation (2 Gy) showed significant memory deficits compared with sham controls. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus increased by 12 h after irradiation. In addition, the numbers of Ki-67- and DCX-positive cells significantly decreased. GT treatment prior to irradiation attenuated memory defects, blocked apoptotic death, as well as reduced the number of DCX-positive cells. Therefore, GT may attenuate memory defects in adult mice exposed to a relatively low dose of radiation possibly by inhibiting the detrimental effects of irradiation on hippocampal neurogenesis.

Evaluation of effect of red ginseng on ovariectomy-induced bone loss in C3H/HeN mice / 동물의과학연구지

Panax ginseng, also known as Korean ginseng, has long been used as a broad tonic in Oriental medicine to augment vitality, health, and longevity, particularly in older people. This study investigated the effects of Korean red ginseng (RG) on bone loss in ovariectomized (OVX) mice. C3H/HeN mice (10-weeks-old) were divided into sham and OVX groups. OVX mice were treated with vehicle, 17beta-estradiol (E2), RG (oral administration, 250 mg/kg/day), or RG (intraperitoneal administration, 50 mg/kg/every other day) for 6 weeks. Serum E2 concentration and alkaline phosphatase (ALP) activity were measured. Tibiae were analyzed using microcomputed tomography. Biomechanical properties and osteoclast surface level were measured. There was no significant difference in the degree of grip strength, body weight, uterine weight, mechanical property, tibiae length, or tibiae weight between the OVX and RG-treated groups. Compared with the OVX group, the serum ALP level was significantly lower in the RG-treated groups. Serum E2 levels and osteoclast surface levels did not change between the OVX and RG-treated groups. RG could not preserve trabecular bone volume, trabecular bone number, trabecular separation, trabecular thickness, structure model index, or bone mineral density of the proximal tibiae metaphysic. In conclusion, there was no definite effect of RG on OVX-induced bone loss in C3H/HeN mice.

Protective effect of diallyl disulfide on cyclophosphamide-induced testicular toxicity in rats / 한국실험동물학회지

This study investigated the protective effects of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced testicular toxicity in male rats. DADS was gavaged to rats once daily for 3 days at 100 mg/kg/day. One hour after the final DADS treatment, the rats were given a single intraperitoneal dose of 150 mg/kg CP. All rats were killed and necropsied on day 56 after CP treatment. Parameters of testicular toxicity included reproductive organ weight, testicular sperm head count, epididymal sperm motility and morphology, epididymal index, and histopathologic examinations. The CP treatment caused a decrease in body weight, testicular sperm head count, epididymal sperm motility, and epididymal index. The histopathological examination revealed various morphological alterations, characterized by degeneration of spermatogonia/spermatocytes, vacuolization, and decreased number of spermatids/spermatocytes in the testis, and cell debris and mild oligospermia in the ductus epididymis. In contrast, DADS pretreatment effectively attenuated the testicular toxicity caused by CP, including decreased sperm head count, epididymal sperm motility, and epididymal index and increased histopathological alterations in the testis and epididymis. These results indicate that DADS attenuates testicular toxicity induced by CP in rats.

4-Week repeated oral dose toxicity study of 1,4-dichlorobutane in rats / 한국실험동물학회지

The present study investigated the potential subacute toxicity of 1,4-dichlorobutane by a 4-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to male rats at dose levels of 0, 100, 300, and 1,000 mg/kg/day for 4 weeks. All rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weight, hematology, serum biochemistry, gross findings, and organ weight were examined. At 1,000 mg/kg/day, an increase in the clinical signs and weights of the liver and kidneys was observed in the male rats. Serum biochemical investigations revealed an increase in alanine aminotransferase, alkaline phosphatase, total cholesterol, total bilirubin, phospholipids, blood urea nitrogen, and gamma glutamyl transferase levels. There were no treatment-related adverse effects in the low and middle-dose groups. In the present experimental conditions, the target organs were determined to be liver and kidney. The no-observed-adverse-effect level was considered to be 300 mg/kg/day in rats.

Establishment of a murine model for radiation-induced bone loss using micro-computed tomography in adult C3H/HeN mice / 한국실험동물학회지

Bone changes are common sequela of radiation therapy for cancer. The purpose of this study was to establish an experimental model of radiation-induced bone loss in adult mice using micro-computed tomography (microCT). The extent of changes following 2 Gy gamma irradiation (2 Gy/min) was studied at 4, 8, 12 or 16 weeks after exposure. Adult mice that received 1, 2, 4 or 6 Gy of gamma-rays were examined 12 weeks after irradiation. Tibiae were analyzed using microCT. Serum markers and biomechanical properties were measured and the osteoclast surface was examined. A significant loss of trabecular bone in tibiae was evident 12 weeks after exposure. Measurements performed after irradiation showed a dose-related decrease in trabecular bone volume fraction (BV/TV) and bone mineral density (BMD), respectively. The best-fitting dose-response curves were linear-quadratic. Taking the controls into accounts, the lines of best fit were as follows: BV/TV (%)= -0.071D2-1.799D+18.835 (r2=0.968, D=dose in Gy) and BMD (mg/cm3) = -3.547D2-14.8D+359.07 (r2=0.986, D=dose in Gy). Grip strength and body weight did not differ among the groups. No dose-dependent differences were apparent among the groups with regard to mechanical and anatomical properties of tibia, serum biochemical markers and osteoclast activity. The findings provide the basis required for better understanding of the results that will be obtained in any further studies of radiation-induced bone responses.