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  • 1.

    【2hr】Tetrabromobisphenol A Induces MMP-9 Expression via NADPH Oxidase and the activation of ROS, MAPK, and Akt Pathways in Human Breast Cancer MCF-7 Cells

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    机译 四溴双酚A通过NADPH氧化酶诱导MMP-9表达，并激活人乳腺癌MCF-7细胞中ROS，MAPK和Akt途径。
    摘要：Tetrabromobisphenol A (TBBPA), the most common industrial brominated flame retardant, acts as a cytotoxic, neurotoxic, and immunotoxicant, causing inflammation and tumors. However, the mechanism of TBBPA-induced matrix metalloproteinase-9 (MMP-9) expression in human breast cancer cells is not clear. In human breast cancer MCF-7 cells, treatment with TBBPA significantly induced the expression and promoter activity of MMP-9. Transient transfection with MMP-9 mutation promoter constructs verified that NF-κB and AP-1 response elements are responsible for the effects of TBBPA. Furthermore, TBBPA-induced MMP-9 expression was mediated by NF-κB and AP-1 transcription activation as a result of the phosphorylation of the Akt and MAPK signaling pathways. Moreover, TBBPA-induced activation of Akt/MAPK pathways and MMP-9 expression were attenuated by a specific NADPH oxidase inhibitor, and the ROS scavenger. These results suggest that TBBPA can induce cancer cell metastasis by releasing MMP-9 via ROS-dependent MAPK, and Akt pathways in MCF-7 cells.
  • 2.

    【2hr】Prevalence of Mycotoxins and Their Consequences on Human Health

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    机译 霉菌毒素的流行及其对人类健康的影响
    摘要：Mycotoxin contamination is a global phenomenon and causes a wide array of negative effects and other complications. This study focused on commonly found mycotoxins in Africa and the possible means of prevention or reduction of their contaminating effects. Mycotoxins are secondary metabolites of mold and fungi; they are generally toxic to living organisms. Hundreds of mycotoxins have been identified thus far, with some, such as aflatoxins, ochratoxins, trichothecenes, zearalenone, fumonisins, and patulin, considered agro-economically important. Several factors contribute to the presence of mycotoxins in food, such as climatic conditions, pest infestation, and poor harvest and storage practices. Exposure to mycotoxins, which occurs mostly by ingestion, leads to various diseases, such as mycotoxicoses and mycoses that may eventually result in death. In light of this, this review of relevant literature focuses on mycotoxin contamination, as well as various methods for the prevention and control of their prevalence, to avert its debilitating consequences on human health. Clear evidence of mycotoxin contamination is present in Africa, and it was therefore recommended that adequate prevention and control of these toxic substances in our food system should be encouraged and that appropriate measures must be taken to ensure food safety as well as the enhanced or long-lifespan of the African populace. Governments, research institutions, and non-governmental organizations should tailor the limited resources available to tackle mycotoxin prevalence, as these will offer the best prospects for successful development of a sustainable food system in Africa.
  • 3.

    【2hr】Thresholds of Genotoxic and Non-Genotoxic Carcinogens

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    机译 遗传毒性和非遗传毒性致癌物阈值
    • 作者：Takehiko Nohmi
    • 刊名：Toxicological Research
    • 2018年第4期
    摘要：Exposure to chemical agents is an inevitable consequence of modern society; some of these agents are hazardous to human health. The effects of chemical carcinogens are of great concern in many countries, and international organizations, such as the World Health Organization, have established guidelines for the regulation of these chemicals. Carcinogens are currently categorized into two classes, genotoxic and non-genotoxic carcinogens, which are subject to different regulatory policies. Genotoxic carcinogens are chemicals that exert carcinogenicity via the induction of mutations. Owing to their DNA interaction properties, there is thought to be no safe exposure threshold or dose. Genotoxic carcinogens are regulated under the assumption that they pose a cancer risk for humans, even at very low doses. In contrast, non-genotoxic carcinogens, which induce cancer through mechanisms other than mutations, such as hormonal effects, cytotoxicity, cell proliferation, or epigenetic changes, are thought to have a safe exposure threshold or dose; thus, their use in society is permitted unless the exposure or intake level would exceed the threshold. Genotoxicity assays are an important method to distinguish the two classes of carcinogens. However, some carcinogens have negative results in in vitro bacterial mutation assays, but yield positive results in the in vivo transgenic rodent gene mutation assay. Non-DNA damage, such as spindle poison or topoisomerase inhibition, often leads to positive results in cytogenetic genotoxicity assays such as the chromosome aberration assay or the micronucleus assay. Therefore, mechanistic considerations of tumor induction, based on the results of the genotoxicity assays, are necessary to distinguish genotoxic and non-genotoxic carcinogens. In this review, the concept of threshold of toxicological concern is introduced and the potential risk from multiple exposures to low doses of genotoxic carcinogens is also discussed.
  • 4.

    【2hr】Quantitative Approaches to Assess Key Carcinogenic Events of Genotoxic Carcinogens

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    机译 评估遗传毒性致癌物关键致癌事件的定量方法
    摘要：Chemical carcinogenesis is a multistep process. Genotoxic carcinogens, which are DNA-reactive, induce DNA adduct formation and genetic alterations in target cells, thereby generating mutated cells (initiation). Subsequently, preneoplastic lesions appear through clonal proliferation of the mutated cells and transform into tumors (promotion and progression). Many factors may influence these processes in a dose-dependent manner. Therefore, quantitative analysis plays an important role in studies on the carcinogenic threshold of genotoxic carcinogens. Herein, we present data on the relationship between key carcinogenic events and their deriving point of departure (PoD). Their PoDs were also compared to those of the carcinogenesis pathway. In an experiment, the liver of rats exposed to 2-amino-3,8-dimethylimidazo-(4,5-f)quinoxaline (MeIQx) was examined to determine the formation of MeIQx-DNA adducts, generation of mutations at LacI transgene, and induction of preneoplastic glutathione S-transferase placental form (GST-P)-positive foci and tumors (benign and malignant). The PoDs of the above key events in the carcinogenicity of MeIQx were increased as the carcinogenesis advanced; however, these PoDs were lower than those of tumor induction. Thus, the order of key events during tumor induction in the liver was as follows: formation of DNA adducts << Mutations << GST-positive foci (preneoplasia) << Tumor (adenoma and carcinoma). We also obtained similar data on the genotoxic and carcinogenic PoDs of other hepatocarcinogens, such as 2-amino-3,8-dimethylimidazo(4,5-f)quinoline. These results contribute to elucidating the existence of a genotoxic and carcinogenic threshold.
  • 5.

    【2hr】Chronological Switch from Translesion Synthesis to Homology-Dependent Gap Repair In Vivo

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    机译 从穿刺合成向体内依赖同源性的间隙修复的时间转换。
    摘要：Cells are constantly exposed to endogenous and exogenous chemical and physical agents that damage their genome by forming DNA lesions. These lesions interfere with the normal functions of DNA such as transcription and replication, and need to be either repaired or tolerated. DNA lesions are accurately removed via various repair pathways. In contrast, tolerance mechanisms do not remove lesions but only allow replication to proceed despite the presence of unrepaired lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS), which is an error-prone strategy and an accurate strategy based on homologous recombination (homology-dependent gap repair [HDGR]). Thus, the mutation frequency reflects the relative extent to which the two tolerance pathways operate in vivo. In the present paper, we review the present understanding of the mechanisms of TLS and HDGR and propose a novel and comprehensive view of the way both strategies interact and are regulated in vivo.
  • 6.

    【2hr】Benchmark Dose Modeling of In Vitro Genotoxicity Data: a Reanalysis

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    机译 体外遗传毒性数据的基准剂量建模：重新分析
    摘要：The methods of applied genetic toxicology are changing from qualitative hazard identification to quantitative risk assessment. Recently, quantitative analysis with point of departure (PoD) metrics and benchmark dose (BMD) modeling have been applied to in vitro genotoxicity data. Two software packages are commonly used for BMD analysis. In previous studies, we performed quantitative dose-response analysis by using the PROAST software to quantitatively evaluate the mutagenicity of four piperidine nitroxides with various substituent groups on the 4-position of the piperidine ring and six cigarette whole smoke solutions (WSSs) prepared by bubbling machine-generated whole smoke. In the present study, we reanalyzed the obtained genotoxicity data by using the EPA’s BMD software (BMDS) to evaluate the inter-platform quantitative agreement of the estimates of genotoxic potency. We calculated the BMDs for 10%, 50%, and 100% (i.e., a two-fold increase), and 200% increases over the concurrent vehicle controls to achieve better discrimination of the dose-responses, along with their BMDLs (the lower 95% confidence interval of the BMD) and BMDUs (the upper 95% confidence interval of the BMD). The BMD values and rankings estimated in this study by using the EPA’s BMDS were reasonably similar to those calculated in our previous studies by using PROAST. These results indicated that both software packages were suitable for dose-response analysis using the mouse lymphoma assay and that the BMD modeling results from these software packages produced comparable rank orders of the mutagenic potency.
  • 7.

    【2hr】Substantial Evidences Indicate That Inorganic Arsenic Is a Genotoxic Carcinogen: a Review

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    机译 大量证据表明无机砷是遗传毒性致癌物：综述
    摘要：Arsenic is one of the most toxic environmental toxicants. More than 150 million people worldwide are exposed to arsenic through ground water contamination. It is an exclusive human carcinogen. Although the hallmarks of arsenic toxicity are skin lesions and skin cancers, arsenic can also induce cancers in the lung, liver, kidney, urinary bladder, and other internal organs. Arsenic is a non-mutagenic compound but can induce significant cytogenetic damage as measured by chromosomal aberrations, sister chromatid exchanges, and micronuclei formation in human systems. These genotoxic end points are extensively used to predict genotoxic potentials of different environmental chemicals, drugs, pesticides, and insecticides. These cytogenetic end points are also used for evaluating cancer risk. Here, by critically reviewing and analyzing the existing literature, we conclude that inorganic arsenic is a genotoxic carcinogen.
  • 8.

    【2hr】Modulation of Inflammatory Cytokines and Islet Morphology as Therapeutic Mechanisms of Basella alba in Streptozotocin-Induced Diabetic Rats

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    机译 炎症细胞因子和胰岛形态的调节，作为链脲佐菌素诱导的糖尿病大鼠中Basella alba的治疗机制
    摘要：The mechanism of the previously reported antidiabetic effect of Basella alba is unknown. This study investigated the role of B. alba aqueous leaf extract in the modulation of inflammatory cytokines and islet morphology in streptozotocin-induced diabetic rats. Forty male Wistar rats, between 8 and 10 weeks old, were randomly divided into four groups (n = 10) and administered the following treatments: Healthy control (H-c) and Diabetic control (D-c) animals received normal saline 0.5 mL/100 g body weight daily, while Healthy Treatment (H-Ba) and Diabetic Treatment (D-Ba) rats received the plant extract 200 mg/kg body weight daily. All treatments were administered by oral gavage. Diabetes was induced in D-c and D-Ba rats by a single intraperitoneal injection of streptozotocin (55 mg/kg body). The body weight and fasting blood sugar (FBS) levels were recorded every week for 4 weeks, after which the rats were euthanized and samples collected for further analysis. After the experiment, FBS level was significantly reduced (p < 0.0001) in rats in the D-Ba group, but increased (p < 0.001) in rats in the D-c group. The absolute (H-c and H-Ba vs D-c, p < 0.05) and relative (D-Ba vs H-c, p < 0.05; D-Ba vs H-Ba, p < 0.005) weights of the pancreases were significantly higher after the experiment. The rats in the D-c group had significantly higher levels of serum interleukin-1β (p < 0.001 vs H-c; p < 0.05 vs H-Ba and D-Ba) and monocyte chemotactic protein-1 (p < 0.0001), but lower levels of interleukin-10 (p < 0.05) in comparison with the other groups. Histopathological examination revealed severe interstitial congestion, reduced islet area (p < 0.0001), and increased islet cell density in the D-c group compared with those in the D-Ba group. From these findings, it was concluded that the aqueous extract of B. alba stimulates the recovery of beta-islet morphology in streptozotocin-induced diabetic rats by modulating the peripheral production of inflammatory cytokines.
  • 9.

    【2hr】Ferulate, an Active Component of Wheat Germ, Ameliorates Oxidative Stress-Induced PTK/PTP Imbalance and PP2A Inactivation

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    机译 阿魏酸，小麦胚芽的活性成分，改善氧化应激诱导的PTK / PTP失衡和PP2A失活
    摘要：Ferulate is a phenolic compound abundant in wheat germ and bran and has been investigated for its beneficial activities. The aim of the present study is to evaluate the efficacy of ferulate against the oxidative stress-induced imbalance of protein tyrosine kinases (PTKs), protein tyrosine phosphatases (PTPs), and serine/threonine protein phosphatase 2A (PP2A), in connection with our previous finding that oxidative stress-induced imbalance of PTKs and PTPs is linked with proinflammatory nuclear factor-kappa B (NF-κB) activation. To test the effects of ferulate on this process, we utilized two oxidative stress-induced inflammatory models. First, YPEN-1 cells were pretreated with ferulate for 1 hr prior to the administration of 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). Second, 20-month-old Sprague-Dawley rats were fed ferulate for 10 days. After ferulate treatment, the activities of PTKs, PTPs, and PP2A were measured because these proteins either directly or indirectly promote NF-κB activation. Our results revealed that in YPEN-1 cells, ferulate effectively suppressed AAPH-induced increases in reactive oxygen species (ROS) and NF-κB activity, as well as AAPH-induced PTK activation. Furthermore, ferulate also inhibited AAPH-induced PTP and PP2A inactivation. In the aged kidney model, ferulate suppressed aging-induced activation of PTKs and ameliorated aging-induced inactivation of PTPs and PP2A. Thus, herein we demonstrated that ferulate could modulate PTK/PTP balance against oxidative stress-induced inactivation of PTPs and PP2A, which is closely linked with NF-κB activation. Based on these results, the ability of ferulate to modulate oxidative stress-related inflammatory processes is established, which suggests that this compound could act as a novel therapeutic agent.
  • 10.

    【2hr】Twenty-Eight-Day Repeated Inhalation Toxicity Study of Aluminum Oxide Nanoparticles in Male Sprague-Dawley Rats

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    机译 雄性Sprague-Dawley大鼠中的氧化铝纳米颗粒28天重复吸入毒性研究
    摘要：Aluminum oxide nanoparticles (Al2O3 NPs) are among the most widely used nanomaterials; however, relatively little information about their risk identification and assessment is available. In the present study, we aimed to investigate the potential toxicity of Al2O3 NPs following repeated inhalation exposure in male Sprague-Dawley rats. Rats were exposed to Al2O3 NPs for 28 days (5 days/week) at doses of 0, 0.2, 1, and 5 mg/m3 using a nose-only inhalation system. During the experimental period, we evaluated the clinical signs, body weight change, hematological and serum biochemical parameters, necropsy findings, organ weight, and histopathology findings. Additionally, we analyzed the bronchoalveolar lavage fluid (BALF), including differential leukocyte counts, and aluminum contents in the major organs and blood. Aluminum contents were the highest in lung tissues and showed a dose-dependent relationship in the exposure group. Histopathology showed alveolar macrophage accumulation in the lungs of rats in the 5 mg/m3 group during exposure and recovery. These changes tended to increase at the end of the recovery period. In the BALF analysis, total cell and neutrophil counts and lactate dehydrogenase, tumor necrosis factor-α, and interleukin-6 levels significantly increased in the 1 and 5 mg/m3 groups during exposure. Under the present experimental conditions, we suggested that the no-observed-adverse-effect level of Al2O3 NPs in male rats was 1 mg/m3, and the target organ was the lung.
  • 11.

    【2hr】Mixture Toxicity of Methylisothiazolinone and Propylene Glycol at a Maximum Concentration for Personal Care Products

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    机译 个人护理用品中最大浓度的甲基异噻唑啉酮和丙二醇的混合物毒性
    摘要：Methylisothiazolinone (MIT) has been used in combination with methylchloroisothiazolinone (CMIT) for cosmetic products such as shampoo, body lotion, and skin care products. The mixture of CMIT/MIT has been found to cause allergic contact dermatitis and is thus no longer permitted for use as a preservative in leave-on cosmetics. However, MIT itself was approved as a stand-alone preservative at a maximum concentration of 100 ppm as the toxicity was derived from CMIT rather than MIT. However, in many countries, allergic skin irritation caused by MIT remains a social concern. In this study, skin irritation was assessed for the presence of MIT, propylene glycol, and their mixture using a 3D human skin model EpiDerm™. Although non-diluted MIT causes serious skin toxicity, skin irritation was not observed at a concentration of 100 ppm, the maximum permissible level for cosmetics and personal care products according to European regulations. Propylene glycol, the most widely used vehicle for MIT, did not cause skin irritation in the 3D skin model. The results are expected to provide information for regulatory policies and guidelines on the use of biocides in consumer products.
  • 12.

    【2hr】Superoxide Dismutase Activity in Small Mesenteric Arteries Is Downregulated by Angiotensin II but Not by Hypertension

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    机译 小肠系膜动脉中的超氧化物歧化酶活性被血管紧张素II下调，但不受高血压的影响
    摘要：Many studies reported reduced antioxidant capacity in the vasculature under hypertensive conditions. However, little is known about the effects of antihypertensive treatments on the regulation of vascular antioxidant enzymes. Thus, we hypothesized that antihypertensive treatments prevent the reduction of antioxidant enzyme activity and expression in the small vessels of angiotensin II-induced hypertensive rats (ANG). We observed the small mesenteric arteries and small renal vessels of normotensive rats (NORM), ANG, and ANG treated with a triple antihypertensive therapy of reserpine, hydrochlorothiazide, and hydralazine (ANG + TTx). Systolic blood pressure was increased in ANG, which was attenuated by 2 weeks of triple therapy (127, 191, and 143 mmHg for NORM, ANG, and ANG + TTx, respectively; p < 0.05). Total superoxide dismutase (SOD) activity in the small mesenteric arteries of ANG was lower than that of NORM. The protein expression of SOD1 was lower in ANG than in NORM, whereas SOD2 and SOD3 expression was not different between the groups. Reduced SOD activity and SOD1 expression in ANG was not restored in ANG + TTx. Both SOD activity and SOD isoform expression in the small renal vessels of ANG were not different from those of NORM. Interestingly, SOD activity in the small renal vessels was reduced by TTx. Between groups, there was no difference in catalase activity or expression in both the small mesenteric arteries and small renal vessels. In conclusion, SOD activity in the small mesenteric arteries decreased by angiotensin II administration, but not by hypertension, which is caused by decreased SOD1 expression.
  • 13.

    【2hr】Erratum to “Distribution of Seven N-Nitrosamines in Food” [Toxicol. Res. 31 (2015) 279–298]

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    机译 关于“食物中7种亚硝胺的分布”的勘误表[毒理学杂志。 Res。 31（2015）279–298]
    摘要：
  • 14.

    【2hr】Erratum to “Anti-Diabetic Effect of Dung Beetle Glycosaminoglycan on db Mice and Gene Expression Profiling” [Toxicol. Res. 34 (2018) 151–162]

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    机译 对“ r虫糖胺聚糖对db小鼠的抗糖尿病作用和基因表达谱的勘误” [毒理学杂志。 Res。 34（2018）151–162]
    摘要：
  • 15.

    【2hr】Systemic and Local Anaphylaxis is Not Induced by Korean Red Ginseng Mixture in Guinea Pigs

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    机译 高丽红参混合物对豚鼠没有全身和局部过敏反应
    摘要：Currently, injuries to customers due to health functional foods are annually increasing. To evaluate the antigenicity of Korean red ginseng mixture (KRGM), we tested for systemic anaphylactic shock and passive cutaneous anaphylaxis in guinea pigs. Based on a comparison of measured body weights, there were no changes in body weight for the KRGM treatment group compared with the control group. In the ovalbumin treated group, however, there was a statistically significant decrease in body weight. For the active systemic anaphylaxis test, after the induction, there were no symptoms that suggested anaphylactic shock in the control and KRGM treatment group. In the ovalbumin treated group, there were symptoms that suggested severe anaphylaxis, and those symptoms included restlessness, piloerection, tremor, rubbing or licking the nose, sneezing, coughing, hyperpnea, dyspnea, staggering gait, jumping, gasping and writhing, convulsion, side position and Cheyne-stokes respiration. All animals died within thirty minutes in the ovalbumin treated group. For the passive cutaneous anaphylaxis test in guinea pigs sensitized to KRGM, each anti-serum was diluted in a stepwise manner. This was followed by an intravenous injection of a mixture of KRGM and Evans blue. The results of the test showed that all the responses were negative in the control and the low-dose and high-dose administration groups. However, in the ovalbumin treated group, all the responses were positive. Based on the above results, there were no anaphylactic responses for up to 12 times the amount of human intake of KRGM in Hartley Guinea-pigs. The results suggest that KRGM is safe as measured by the systemic and local antigenicity in guinea pigs.
  • 16.

    【2hr】A Collaborative Study to Establish the Second Korean National Reference Standard for Snake Venom

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    机译 建立第二个韩国蛇毒国家参考标准的合作研究
    摘要：In 2015, a candidate for the second national reference standard (NRS) of Gloydius snake venom was produced to replace the first NRS of Gloydius snake venom. In the present study, the potencies of the candidate were determined by a collaborative study, and the qualification of the candidate was estimated. The potencies of the candidate were determined by measuring the murine lethal titers and lapine hemorrhagic titers of venom against the regional working reference standard (RWRS) for antivenom using the methods described in the previous report for the first NRS of Gloydius snake venom. Three Korean facilities contributed data from a total of 30 independent assays. Subsequently, two foreign national control research laboratories contributed to this collaborative study. The results were calculated using the Reed-Muench method for lethality and determined using a mixed-effects model for hemorrhage. The general common potencies of the lethal and hemorrhagic titers were obtained from the results of the 30 tests performed at three Korean facilities. The results are expressed in micrograms for 1 test dose (TD) with a 95% confidence interval as follows: a lethal titer of 90.13 μg/TD (95% confidence interval = 87.39~92.86 μg) and a hemorrhagic titer of 10.80 μg/TD (95% confidence interval = 10.46~11.14 μg). In addition, the candidate preparation showed good quality evaluation according to the results of the quality estimation of the candidate and is judged to be suitable to serve as the Korean NRS for snake venom. In conclusion, the second NRS of Gloydius snake venom was established in this study and will be used for national quality control, including a national lot release test of Korean antivenom products.
  • 17.

    【2hr】Metabolic Profiling of Eccentric Exercise-Induced Muscle Damage in Human Urine

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    机译 偏心运动引起的人体尿液肌肉损伤的代谢谱分析
    摘要：Skeletal muscle can be ultrastructurally damaged by eccentric exercise, and the damage causes metabolic disruption in muscle. This study aimed to determine changes in the metabolomic patterns in urine and metabolomic markers in muscle damage after eccentric exercise. Five men and 6 women aged 19~23 years performed 30 min of the bench step exercise at 70 steps per min at a determined step height of 110% of the lower leg length, and stepping frequency at 15 cycles per min. 1H NMR spectral analysis was performed in urine collected from all participants before and after eccentric exercise-induced muscle damage conventionally determined using a visual analogue scale (VAS) and maximal voluntary contraction (MVC). Urinary metabolic profiles were built by multivariate analysis of principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) using SIMCA-P. From the OPLS-DA, men and women were separated 2 hr after the eccentric exercise and the separated patterns were maintained or clarified until 96 hr after the eccentric exercise. Subsequently, urinary metabolic profiles showed distinct trajectory patterns between men and women. Finally, we found increased urinary metabolites (men: alanine, asparagine, citrate, creatine phosphate, ethanol, formate, glucose, glycine, histidine, and lactate; women: adenine) after the eccentric exercise. These results could contribute to understanding metabolic responses following eccentric exercise-induced muscle damage in humans.
  • 18.

    【2hr】Oxidative Stress in Extrahepatic Tissues of Rats Co-Exposed to Aflatoxin B1 and Low Protein Diet

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    机译 黄曲霉毒素B1和低蛋白饮食共同暴露的大鼠肝外组织的氧化应激
    摘要：Early life exposure to aflatoxin B1 (AFB1) and low protein diet through complementary foods during weaning is common in parts of Africa and Asia. This study evaluated the effect of co-exposure to AFB1 and low protein diet on the extrahepatic tissues of rats. Twenty-four three-week old weanling male albino rats were used for this study and were randomly assigned into four groups: group 1 served as control and was fed normal protein diet (20% protein), group 2 was fed low protein diet (5% protein), group 3 was fed normal protein diet + 40 ppb AFB1 while group 4 received low protein diet + 40 ppb AFB1, all for eight weeks. Afterward, biomarkers of anemia (packed cell volume (PCV), hemoglobin) and kidney function (urea, uric acid, and creatinine) were determined in the blood while biomarkers of oxidative stress were determined in the tissues spectrophotometrically. Co-exposure to AFB1 and low protein diet significantly (p < 0.05) decreased body weight gain and PCV, increased biomarkers of kidney functions and induced oxidative stress in the tissues studied. There was significant (p < 0.05) reduction in glutathione concentration while TBARS was significantly increased in the tissues. Co-exposure to AFB1 and low protein diet had additive effects on decreasing the weight gain and potentiation effect of kidney dysfunction in the rats. The co-exposure also decreased antioxidant enzymes and increased oxidant status in the tissues. Our results demonstrate that this co-exposure has deleterious health effects on extrahepatic tissues and should be a public health concern especially in developing countries where AFB1 contamination is common.
  • 19.

    【2hr】Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study

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    机译 研究替诺福韦和替诺福韦纳米颗粒对肝脏和肾脏的器官毒性特征：实验动物研究
    摘要：Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman’s space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.
  • 20.

    【2hr】Modulatory Role of Selenium and Vitamin E, Natural Antioxidants, against Bisphenol A-Induced Oxidative Stress in Wistar Albinos Rats

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    机译 硒和维生素E，天然抗氧化剂对双酚A诱导的Wistar Albinos大鼠氧化应激的调节作用
    摘要：Bisphenol A, an everywhere chemical, is applied as a plasticizer in polycarbonate plastics, which often used in our everyday products and in epoxy resins as protective coatings and linings for food and beverage cans for decades. Human exposure to BPA may lead to adverse effects by interfering with oestrogen receptors. Our present study was conducted to investigate the protective effects of selenium (Se) and vitamin E (Vit E) on BPA-induced damage in the liver of male rats. Animals were randomly divided into four groups: the first group received olive oil and served as control. The second group received both (Se + Vit E) (0.5 mg/kg diet; 100 mg/kg of diet). The third one treated orally by (10 mg/kg b.w.) of BPA. The last group received (Se + Vit E) (0.5 mg/kg diet; 100 mg/kg of diet) concomitantly with (10 mg/kg b.w.) BPA. Exposure to BPA for three weeks engendered a hepatic disorder. An increased AST and ALT enzymatic activity was noticed in BPA-treated group as compared to other groups. Furthermore, a change in glucose, cholesterol, LDL-C, HDL-C, albumin, and bilirubin level was remarkable. Moreover, exposure to BPA increased malondialdehyde levels while reduced gluthatione content was decreased in the liver homogenate. A decrease in glutathione peroxidase, glutathione s-transferase and catalase activities was observed in the same group. Administration of selenium and vitamin E through the diet in BPA treated rats ameliorated the biochemical parameters cited above. In addition, an improvement in activities of liver enzymes was recorded. The histological findings confirmed the biochemical results. The model of this study that we employed characterized the relationships between BPA-induced hepatotoxicity and its alleviation by natural antioxidants like selenium and vitamin E.
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