Toxicological ResearchPub Date : 2022-09-02eCollection Date: 2023-01-01DOI: 10.1007/s43188-022-00153-1
Daram Yang, Jong Won Kim, Hyuneui Jeong, Min Seok Kim, Chae Woong Lim, Kyuhong Lee, Bumseok Kim
{"title":"Effects of maternal cigarette smoke exposure on the progression of nonalcoholic steatohepatitis in offspring mice.","authors":"Daram Yang, Jong Won Kim, Hyuneui Jeong, Min Seok Kim, Chae Woong Lim, Kyuhong Lee, Bumseok Kim","doi":"10.1007/s43188-022-00153-1","DOIUrl":"10.1007/s43188-022-00153-1","url":null,"abstract":"<p><p>Cigarette smoke (CS) is a dominant carcinogenic agent in a variety of human cancers. CS exposure during pregnancy can adversely affect the fetus. Non-alcoholic fatty liver disease (NAFLD) is considered as a hepatic manifestation of a metabolic disorder, and ranges from simple steatosis to cirrhosis leading to hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is a more severe phase of NAFLD. Recently, there is increasing apprehension about the CS-related chronic liver diseases. Therefore, we examined whether maternal CS exposure could affect the pathogenesis of NASH in offspring. Mainstream CS (MSCS) was exposed to pregnant C57BL/6 mice via nose-only inhalation for 2 h/day, 5 days/week for 2 weeks from day 6 to 17 of gestation at 0, 300, or 600 μg/L. Three-week-old male offspring mice were fed methionine and choline-supplemented (MCS) diet or methionine and choline-deficient including high-fat (MCDHF) diet for 6 weeks to induce NASH. Maternal MSCS exposure increased the severity of NASH by increasing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic total cholesterol (TC) and triglyceride (TG) levels, pro-inflammation, fibrosis, and steatosis in offspring mice. Especially, maternal MSCS exposure significantly downregulated the phosphorylation of AMP-activated protein kinase (AMPK) in MCDHF diet-fed offspring mice. Subsequently, the protein levels of sterol regulatory element-binding protein (SREBP)-1c and stearoyl-CoA desaturase-1 (SCD1) were upregulated by maternal MSCS exposure. In conclusion, maternal MSCS exposure exacerbates the progression of NASH by modulating lipogenesis on offspring mice.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00153-1.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"91-103"},"PeriodicalIF":2.3,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hong-Gyu An, Sangyun Shin, Boyoung Lee, Yeonju Kwon, Tae-Uk Kwon, Yeo-Jung Kwon, Young-Jin Chun
{"title":"Induction of synergistic apoptosis by tetramethoxystilbene and nutlin-3a in human cervical cancer cells.","authors":"Hong-Gyu An, Sangyun Shin, Boyoung Lee, Yeonju Kwon, Tae-Uk Kwon, Yeo-Jung Kwon, Young-Jin Chun","doi":"10.1007/s43188-022-00150-4","DOIUrl":"10.1007/s43188-022-00150-4","url":null,"abstract":"<p><p>2,4,3',5'-Tetramethoxystilbene (TMS) is a selective inhibitor of cytochrome P450 1B1 to block the conversion from estradiol to 4-OH-estradiol. Several studies suggested that TMS may act as a potent anti-cancer agent for hormone-related cancer including cervical cancer. Nutlin-3a is a cis-imidazoline analog that interferes with the interaction between mouse double minute 2 homolog (MDM2) and the tumor suppressor p53. The purpose of the study was to compare the cytotoxic effect of TMS and nutlin-3a treatment individually and in combination in HeLa cells. To assess the potential synergistic effects between TMS and nutlin-3a, low concentrations of TMS and nutlin-3a were simultaneously treated in HeLa cells. Based on cell viability, apoptosis assays, and the increase in cleaved caspase-3 and poly (ADP-ribose) polymerase cleavage, it was demonstrated that the combination with TMS and nutlin-3a exerts a synergistic effect on cancer cell death. Isobologram analysis of HeLa cells noted synergism between TMS and nutlin-3a. The combined treatment increased the expression of mitochondrial pro-apoptotic factors such as Bax and Bak, and decreased the expression of the XIAP. In addition, combination treatment significantly enhanced the translocation of AIF to the nucleus in HeLa cells. In conclusion, the results demonstrate that the combination of TMS and nutlin-3a induces synergistic apoptosis in HeLa cells, suggesting the possibility that this combination can be applied as a novel therapeutic strategy for cervical cancer.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"38 4","pages":"591-600"},"PeriodicalIF":2.3,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532473/pdf/43188_2022_Article_150.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40677049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2022-08-22eCollection Date: 2022-10-01DOI: 10.1007/s43188-022-00144-2
Minjeong Kim, Kyung-Min Lim
{"title":"Melanocytotoxic chemicals and their toxic mechanisms.","authors":"Minjeong Kim, Kyung-Min Lim","doi":"10.1007/s43188-022-00144-2","DOIUrl":"10.1007/s43188-022-00144-2","url":null,"abstract":"<p><p>Melanocyte cell death can lead to various melanocyte-related skin diseases including vitiligo and leukoderma. Melanocytotoxic chemicals are one of the most well-known causes of nongenetic melanocyte-related diseases, which induce melanocyte cell death through apoptosis. Various chemicals used in cosmetics, medicine, industry and food additives are known to induce melanocyte cell death, which poses a significant risk to the health of consumers and industrial workers. This review summarizes recently reported melanocytotoxic chemicals and their mechanisms of toxicity in an effort to provide insight into the development of safer chemicals.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"38 4","pages":"417-435"},"PeriodicalIF":1.6,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532501/pdf/43188_2022_Article_144.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40655039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2022-08-22eCollection Date: 2023-01-01DOI: 10.1007/s43188-022-00146-0
Soo Jin Kim, Kyunghyeon Lee, Jaewoo Park, Miso Park, U Ji Kim, Se-Mi Kim, Keun Ho Ryu, Keon Wook Kang
{"title":"CKD-516 potentiates the anti-cancer activity of docetaxel against epidermal growth factor receptor tyrosine kinase inhibitor-resistant lung cancer.","authors":"Soo Jin Kim, Kyunghyeon Lee, Jaewoo Park, Miso Park, U Ji Kim, Se-Mi Kim, Keun Ho Ryu, Keon Wook Kang","doi":"10.1007/s43188-022-00146-0","DOIUrl":"10.1007/s43188-022-00146-0","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer death. Although docetaxel has been used as a second- or third-line treatment for non-small cell lung cancer (NSCLC), the objective response rate is less than 10%. Hence, there is a need to improve the clinical efficacy of docetaxel monotherapy; combination therapy should be considered. Here, we show that CKD-516, a vascular disruption agent, can be combined with docetaxel to treat epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-resistant NSCLC. CKD-516 was orally bioavailable; neither CKD-516 nor docetaxel affected the mean plasma concentration-time profile or pharmacokinetic parameters of the other drug. CKD-516 and docetaxel synergistically inhibited the growth of H1975 (with an L858R/T790M double mutation of EGFR) and A549 (with a KRAS mutation) lung cancer cell lines. In addition, docetaxel plus CKD-516 delayed tumor growth in-and extended the lifespan of-tumor-bearing mice. Thus, combination CKD-516 and docetaxel therapy could be used to treat EGFR-TKI-resistant NSCLC.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"61-69"},"PeriodicalIF":2.3,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10641720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2022-08-09eCollection Date: 2023-01-01DOI: 10.1007/s43188-022-00147-z
Jihyun Keum, Ki-Young Ryu, Jaesook Roh
{"title":"Radioactive Iodine-induced hypothyroidism interferes with the maturation of reproductive organs during puberty in immature female rats.","authors":"Jihyun Keum, Ki-Young Ryu, Jaesook Roh","doi":"10.1007/s43188-022-00147-z","DOIUrl":"10.1007/s43188-022-00147-z","url":null,"abstract":"<p><p>Animal and human studies suggest that thyroid hormone may have critical roles in the development of the ovary. For example, thyroid deficiency disrupts the ovarian microarchitecture and menstrual cycle in neonate and adult women, respectively. Therefore, it is conceivable that thyroid deficiency might disrupt sexual maturation during the peri-pubertal period. To investigate the impact of radioactive iodine-induced thyroid deficiency on reproductive organs throughout puberty, immature female rats were given water containing radioactive iodine (0.37 MBq/g body weight) twice, on postnatal days 22 and 29. Radioactive iodine-induced hypothyroidism was revealed by low free thyroxin levels. Thyroid deficiency delayed the onset of vaginal opening, reduced ovarian weight and the number of medium-sized follicles and led to elongated uteri. However, there was no effect on the estrous cycle or absolute uterus weight. We conclude that radioactive iodine-induced thyroid deficiency delays sexual maturation and alters normal ovarian growth in peri-pubertal rats.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"53-60"},"PeriodicalIF":1.6,"publicationDate":"2022-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10641716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2022-07-29eCollection Date: 2023-01-01DOI: 10.1007/s43188-022-00145-1
Chilly Gay Remonde, Edson Luck Gonzales, Keremkleroo Jym Adil, Se Jin Jeon, Chan Young Shin
{"title":"Augmented impulsive behavior in febrile seizure-induced mice.","authors":"Chilly Gay Remonde, Edson Luck Gonzales, Keremkleroo Jym Adil, Se Jin Jeon, Chan Young Shin","doi":"10.1007/s43188-022-00145-1","DOIUrl":"10.1007/s43188-022-00145-1","url":null,"abstract":"<p><p>Febrile seizure (FS) is one of the most prevalent etiological events in childhood affecting 2-5% of children from 3 months to 5 years old. Debates on whether neurodevelopmental consequences rise in later life following a febrile seizure or not are still ongoing however there is limited evidence of its effect, especially in a laboratory setting. Moreover, the comparative study using both male and female animal models is sparse. To examine the effect of FS on the behavioral features of mice, both sexes of ICR mice were induced with hyperthermic seizures through exposure to an infrared heat lamp. The mice were divided into two groups, one receiving a single febrile seizure at postnatal day 11 (P11) and one receiving three FS at P11, P13, and P15. Starting at P30 the FS-induced mice were subjected to a series of behavioral tests. Mice with seizures showed no locomotor and motor coordination deficits, repetitive, and depressive-like behavior. However, the FS-induced mice showed impulsive-like behavior in both elevated plus maze and cliff avoidance tests, which is more prominent in male mice. A greater number of mice displayed impaired CAT in both males and females in the three-time FS-induced group compared to the single induction group. These results demonstrate that after induction of FS, male mice have a higher susceptibility to consequences of febrile seizure than female mice and recurrent febrile seizure has a higher chance of subsequent disorders associated with decreased anxiety and increased impulsivity. We confirmed the dysregulated expression of impulsivity-related genes such as 5-HT1A and tryptophan hydroxylase 2 from the prefrontal cortices of FS-induced mice implying that the 5-HT system would be one of the mechanisms underlying the increased impulsivity after FS. Taken together, these findings are useful in unveiling future discoveries about the effect of childhood febrile seizure and the mechanism behind it.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"37-51"},"PeriodicalIF":2.3,"publicationDate":"2022-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10696115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2022-07-22eCollection Date: 2023-01-01DOI: 10.1007/s43188-022-00141-5
Cheol Park, Hyesook Lee, Sung Ok Kim, Eun-Woo Lee, Hyun-Tai Lee, Hyun Ju Kwon, Byung Woo Kim, Gi-Young Kim, Mi Ryeo Kim, Yung Hyun Choi
{"title":"The preventive effect of <i>Mori Ramulus</i> on oxidative stress-induced cellular damage in skeletal L6 myoblasts through Nrf2-mediated activation of HO-1.","authors":"Cheol Park, Hyesook Lee, Sung Ok Kim, Eun-Woo Lee, Hyun-Tai Lee, Hyun Ju Kwon, Byung Woo Kim, Gi-Young Kim, Mi Ryeo Kim, Yung Hyun Choi","doi":"10.1007/s43188-022-00141-5","DOIUrl":"10.1007/s43188-022-00141-5","url":null,"abstract":"<p><p>The aim of the present study is to investigate the preventive effect of water extract of <i>Mori Ramulus</i> (MRWE) on oxidative stress-mediated cellular damages in rat skeletal L6 myoblasts. Our results demonstrated that MRWE pretreatment markedly improved cell survival and suppressed cell cycle arrest at the G2/M phase and apoptosis in hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-treated L6 cells. H<sub>2</sub>O<sub>2</sub>-triggered DNA damage was also notably reduced by MRWE, which since it was correlated with protection of reactive oxygen species (ROS) production. Additionally, H<sub>2</sub>O<sub>2</sub> stimulated cytosolic release of cytochrome <i>c</i> and up-regulation of Bax/Bcl-2 ratio, whereas MRWE suppressed these changes following by H<sub>2</sub>O<sub>2</sub>. Moreover, MRWE inhibited the cleavage of poly(ADP-ribose) polymerase as well as the activity of caspase-3 by H<sub>2</sub>O<sub>2</sub>. Furthermore, MRWE enhanced H<sub>2</sub>O<sub>2</sub>-mediated expression of nuclear factor erythroid 2-associated factor 2 (Nrf2) and its representative downstream enzyme, heme oxygenase-1 (HO-1). However, the protective effects of MRWE on H<sub>2</sub>O<sub>2</sub>-induced ROS production, cell cycle arrest and apoptosis were significantly attenuated by HO-1 inhibitor. In conclusion, our present results suggests that MRWE could protect L6 myoblasts from H<sub>2</sub>O<sub>2</sub>-induced cellular injury by inhibiting ROS generation along with Nrf2-mediated activation of HO-1, indicating this finding may expand the scope of application of <i>Mori Ramulus</i> in medicine.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"25-36"},"PeriodicalIF":2.3,"publicationDate":"2022-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10641715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicological ResearchPub Date : 2022-07-19eCollection Date: 2023-01-01DOI: 10.1007/s43188-022-00143-3
Min-Seok Choi, Seoyoung Kim, Si Eun Lee, Sanghyeon Yeon, Sanghee Park, Jun Yong Yang, Susun An
{"title":"Algorithm for environmental risk assessment of cosmetics to reduce their environmental impact.","authors":"Min-Seok Choi, Seoyoung Kim, Si Eun Lee, Sanghyeon Yeon, Sanghee Park, Jun Yong Yang, Susun An","doi":"10.1007/s43188-022-00143-3","DOIUrl":"10.1007/s43188-022-00143-3","url":null,"abstract":"<p><p>Cosmetics, especially rinse-off personal care products (PCPs), such as shampoo, facial cleanser, and body wash, are composed of various chemicals and are one of the sources of chemicals released into aquatic ecosystems. Therefore, the cosmetic industry strives to reduce the impact of their products on the aquatic environment. In this study, we proposed an algorithm based on persistence, bioaccumulation potential, and toxicity (PBT) for the environmental risk assessment of cosmetics. PBT features are generally used in the evaluation of the environmental impact of chemicals. Based on the PBT assessment, it is possible to predict the short- and long-term effects of chemicals on the environment. Our algorithm derives substance and product scores from PBT features, allowing for the risk assessment of each ingredient in the product. Furthermore, we proposed a criterion for the environmental impact grade through which each component can be classified. We intend to use this grade and factors determined through the algorithm to manufacture products with low environmental impact.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"15-24"},"PeriodicalIF":2.3,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chemokine expression in human 3-dimensional cultured epidermis exposed to PM2.5 collected by cyclonic separation.","authors":"Maori Kono, Tomoaki Okuda, Nami Ishihara, Hiroyuki Hagino, Yuto Tani, Hiroshi Okochi, Chiharu Tokoro, Masayuki Takaishi, Hidefumi Ikeda, Yasuhiro Ishihara","doi":"10.1007/s43188-022-00142-4","DOIUrl":"10.1007/s43188-022-00142-4","url":null,"abstract":"<p><p>Fine particulate matter (PM2.5) exposure has a risk of inducing several health problems, especially in the respiratory tract. The skin is the largest organ of the human body and is therefore the primary target of PM2.5. In this study, we examined the effects of PM2.5 on the skin using a human 3-dimensional cultured epidermis model. PM2.5 was collected by cyclonic separation in Yokohama, Japan. Global analysis of 34 proteins released from the epidermis revealed that the chemokines, chemokine C-X-C motif ligand 1 (CXCL1) and interleukin 8 (IL-8), were significantly increased in response to PM2.5 exposure. These chemokines stimulated neutrophil chemotaxis in a C-X-C motif chemokine receptor 2-dependent manner. The oxidative stress and signal transducer and activator of transcription 3 pathways may be involved in the increased expression of CXCL1 and IL-8 in the human epidermis model. Interestingly, in the HaCaT human keratinocyte cell line, PM2.5 did not affect chemokine expression but did induce IL-6 expression, suggesting a different effect of PM2.5 between the epidermis model and HaCaT cells. Overall, PM2.5 could induce the epidermis to release chemokines, followed by neutrophil activation, which might cause an unregulated inflammatory reaction in the skin.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"1-13"},"PeriodicalIF":2.3,"publicationDate":"2022-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeong-Won Kim, Hyunjun Kim, Hyunjin Park, Ji-Soo Yoon, Myeong-Il Kim, Je-Won Ko, Tae-Won Kim
{"title":"Repeated oral dose toxicity and genotoxicity of a standardized <i>Quisqualis indica</i> extract.","authors":"Jeong-Won Kim, Hyunjun Kim, Hyunjin Park, Ji-Soo Yoon, Myeong-Il Kim, Je-Won Ko, Tae-Won Kim","doi":"10.1007/s43188-022-00140-6","DOIUrl":"10.1007/s43188-022-00140-6","url":null,"abstract":"<p><p><i>Quisqualis indica</i> L. of Combretaceae family is a traditional medicine that is widely used for various gastrointestinal discomfort including stomach pain, constipation, and digestive problem. In this study, the potential repeated dose toxicity and genotoxicity of a standardized <i>Quisqualis indica</i> L. extract (HU033) were determined under good laboratory practice conditions. For the repeated dose toxicity test, HU033 was orally administered to Sprague-Dawley (SD) rats at doses of 500, 1000, and 2000 mg/kg/day for 13 consecutive weeks. The genotoxicity of HU033 was determined with a standard battery of genotoxicity test, including an in vitro bacterial reverse mutation test, an in vitro chromosomal aberration test, and an in vivo micronucleus test. After 13 weeks of repeated dose of HU033 by oral administration, there was no treatment related adverse clinical sign including food consumption, organ weights, and histopathological findings or significant decrement in bodyweight. The no-observed-adverse-effect level of HU033 was higher than 2000 mg/kg in both male and female SD rats. No target organs were identified. In addition, no evidence of HU033 genotoxicity was detected based on results from the bacterial reverse mutation test, chromosomal aberration test, and micronucleus test. Based on results of this study, HU033 could be safely used in food and medical products within the tested dose range.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"38 4","pages":"577-589"},"PeriodicalIF":2.3,"publicationDate":"2022-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532493/pdf/43188_2022_Article_140.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40653553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}