Assessment of acute inhalation toxicity of citric acid and sodium hypochlorite in rats

Background@#Citric acid (CA) and sodium hypochlorite (NaOCl) have been used to disinfect animals to protect them against avian influenza and foot-and-mouth disease. @*Objectives@#We performed a good laboratory practice (GLP)-compliant animal toxicity study to assess the acute toxic effects of CA and NaOCl aerosol exposure in Sprague-Dawley rats. @*Methods@#Groups of five rats per sex were exposed for 4 h to four concentrations of the two chemicals, i.e., 0.00, 0.22, 0.67, and 2.00 mg/L, using a nose-only exposure. After a single exposure to the chemicals, clinical signs, body weight, and mortality was observed during the observation period. On day 15, an autopsy, and then gross findings, and histopathological analysis were performed. @*Results@#After exposure to CA and NaOCl, body weight loss was observed but recovered.Two males died in the CA 2.00 mg/L group and, two males and one female died in the 2.00 mg/L NaOCl group. In the gross findings and histopathological analysis, discoloration of the lungs was observed in the CA exposed group and inflammatory lesions with discoloration of the lungs were observed in the NaOCl exposed group. These results suggest that the lethal concentration 50 (LC50) of CA is 1.73390 mg/L for males and > 1.70 mg/L for females. For NaOCl, the LC50 was 2.22222 mg/L for males and 2.39456 mg/L for females. @*Conclusions@#The Globally Harmonized System is category 4 for both CA and NaOCl. In this study, the LC50 results were obtained through a GLP-based acute inhalation toxicity assessment. These results provide useful data to reset safety standards for CA and NaOCl use.

International regulatory considerations pertaining to the development of stem cell-based veterinary medicinal products

Stem cell-based products (SCPs) are an emerging field of veterinary medicine that focuses on the regeneration, repair, or replacement of damaged tissues or organs. However, there are some issues in applying the traditional regulatory guideline for the approval of SCPs as veterinary medicinal products. This article describes the positions of Korea, US, and EU regarding SCPs, and compares the regulatory guidelines of each country for their safety evaluation. Although there are some differences in the regulatory guidelines, similar considerations in identifying the quality of SCPs and their safety has adopted. Overall, these guidelines need to be harmonized among countries.

Identification of urinary microRNA biomarkers for in vivo gentamicininduced nephrotoxicity models

Background@#Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers. @*Objectives@#In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity. @*Methods@#For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats. @*Results@#GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis.We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules.Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein. @*Conclusions@#These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

Guideline on safety evaluation of cell-based medicinal products for animal use

With the increased use of cell therapy in the veterinary sector, there is a growing demand for the development of cell-based medicinal products and the determination of their safety. Currently, the Korean Animal and Plant Quarantine Agency has established a guideline for evaluating the safety of cell-based medicinal products for animal use. The guideline includes items related to definition, classification, management, manufacturing procedure and quality control (standard and test method), stability testing, toxicity testing, pharmacological testing, and performance of clinical trials. In addition, testing protocols related to safety assessment of animal cell-based products such as chromosome karyotyping, tumorigenicity testing, confirmatory testing of biodistribution and kinetics, and target animal safety testing are described in detail. Moreover, because cell-based medicinal products are novel therapies, deviations from traditional designs may be justified in order to obtain relevant safety information on the treatment. Additionally, this guideline can be amended on the basis of new scientific findings.

Therapeutic effect of topical application of curcumin during treatment of radiation burns in a mini-pig model

Curcumin protects the skin against radiation-induced epidermal damage and prevents morphological changes induced by irradiation skin, thereby maintaining the epidermal thickness and cell density of basal layers. In this study, the effects of topical curcumin treatment on radiation burns were evaluated in a mini-pig model. Histological and clinical changes were observed five weeks after radiation exposure to the back (⁶⁰Co gamma-radiation, 50 Gy). Curcumin was applied topically to irradiated skin (200 mg/cm²) twice a day for 35 days. Curcumin application decreased the epithelial desquamation after irradiation. Additionally, when compared to the vehicle-treated group, the curcumin-treated group showed reduced expression of cyclooxygenase-2 and nuclear factor-kappaB. Furthermore, irradiation prolonged healing of biopsy wounds in the exposed area, whereas curcumin treatment stimulated wound healing. These results suggest that curcumin can improve epithelial cell survival and recovery in the skin and therefore be used to treat radiation burns.

Hair Growth Promoting Potential of Phospholipids Purified from Porcine Lung Tissues

BP201, porcine lung tissue-derived phospholipids, consists of phosphatidylcholine as a major phospholipid species. BP201 promoted hair growth after application onto the shaved backs of BALB/c and C3H mice. Its effect was enhanced when applied together with minoxidil (MNX) in C3H mice. When the tissue specimens prepared from the shaved skins of BP201-treated and control mice were microscopically examined, the total numbers of hair follicles in both anagen and telogen phases of BP201-treated mice were significantly higher than those of control mice. The numbers of hair follicles in the anagen phase of BP201-treated mice were also higher than those of control mice. In combination with MNX, BP201 further increased the total number of hair follicles, but did not alter the percentage of hair follicles in the anagenic phase. BP201 also increased the proliferation of human hair follicle dermal papilla cells. Collectively, BP201 possesses hair growth promoting potential, which would suggest its use singly or in combination for hair growth products.

Embryonal rhabdomyosarcoma in the abdominal cavity of an aged Sprague-Dawley rat / 대한수의학회지

We report a spontaneous embryonal rhabdomyosarcoma in the abdominal cavity of an aged (88-week-old) Sprague-Dawley rat. The animal had a firm lobulated 5 x 5 x 4.5 cm mass in the abdominal cavity that was whitish to tan with necrotic and hemorrhagic plaques. Microscopically, the mass contained nodules with spindle or globoid shaped neoplastic cells with abundant eosinophilic cytoplasm and round or elongated nuclei mixed with other spindle cells with a filamentous appearance and scanty cytoplasm. Multinucleated cells and cross-striations were also observed. The neoplastic cells were positive for vimentin, desmin, and alpha-smooth muscle actin, especially the small spindle cells.

Uterine leiomyosarcoma in a wild rat (Rattus norvegicus): usefulness of Ki-67 labeling index for diagnosis / 한국실험동물학회지

Uterine smooth muscle tumor is very rare in laboratory rats and, there has been no report in the wild rodents. Among a total of 400 wild rats captured in Gyeonggi, Gangwon, and Chungbuk provinces of Korea in 2007, 2010, and 2011, we found a uterine spindle cell tumor, diagnosed as smooth muscle cell origin based on differential features of histology and immunohistochemistry. Its incidence was very low, like in the laboratory rats, as under 0.5% for female. Considering generally applied histological and cellular criteria, this case was difficult in differential diagnosis between benign and malignant. Ki-67 labeling index was therefore further investigated, and it ranged from 26.4 to 37.6% in the 10 different areas, representing an average of 32.9+/-0.05%. The Ki-67 labeling index of neoplastic cells near the necrotic area was recorded as 83.5%. According to such high Ki-67 labeling index, it was more likely a malignant leiomyosarcoma, assenting to the previous proposal that Ki-67 labeling index is a significant criterion to differentiate between malignant and benign in the smooth muscle tumors.

Expression of ErbB receptors in the pre-pubertal and pubertal virgin mammary glands of dairy cows / 대한수의학회지

In the present study, we investigated the expression patterns of ErbB family proteins in the pre-pubertal and pubertal mammary glands of dairy cows in association with gland development. For this study, we performed immunohistochemistry for ErbB-1-4 and Ki-67 cell proliferation marker. We found that the pre-pubertal and pubertal mammary glands had typical structures, including ducts and terminal end buds embedded in the stroma, and no development of lobuloalveolar structures. On immunohistochemistry, ErbB-2 and ErbB-3 were strongly expressed in the cytoplasm and nuclei in the epithelial cells of mammary ducts and terminal end buds, and stromal cells, whereas ErbB-1 and ErbB-4 were weakly expressed only in the cytoplasm of gland epithelium and stromal cells, irrespective of the developmental stage. Cell proliferation was inactive in the mammary gland cell compartments in both phases. Thus, expression of the ErbB family in the developing mammary glands was not associated with their functional effects, such as cell proliferation and lobuloalveolar development. In conclusion, ErbB receptors were differentially expressed in the epithelial and stromal cells of virgin mammary glands of dairy cows. Compared with rodent mammary glands, ErbB-3 and ErbB-4 were found to be highly expressed in bovine mammary glands.