Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas

The aim of this study was to investigate the potential protective role of fullerenol C60(OH)24 on doxorubicin-induced liver toxicity using in vivo (female Sprague-Dawley rats) and in vitro (human hepatocellular carcinoma - HepG2; colorectal adenocarcinoma cell lines - Caco-2) approaches. The first (healthy control) and second (control with chemically induced mammary carcinomas) group received saline only. The third, fourth and fifth group (all with breast cancer) were injected (i.p.) with a single dose of doxorubicin (8mg/kg), doxorubicin/fullerenol (100mg/kg of fullerenol 30min before administration of 8mg/kg doxorubicin) and fullerenol (100mg/kg), respectively. Two days after treatment, the rats were sacrificed. Results showed that treatment with doxorubicin alone caused significant changes in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), as well as in the levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) in the liver tissue. These effects were significantly reduced for all investigated parameters by pre-treatment with fullerenol but not for the MDA and GSH level. The HepG2 and Caco-2 cell lines were continuously treated with fullerenol for 12h, 24h, 48h and 96h at concentrations of 10microg/mL and 44microg/mL. With the aim of evaluating the modulating activity of fullerenol on doxorubicin-induced hepatotoxicity, the cell lines were simultaneously treated with doxorubicin (1microm; 5microm) and fullerenol (10microg/mL; 44microg/mL) in different combinations. When the cells are treated with 5microm doxorubicin along with the fullerenol, we can see a significant improvement of the cell capability during the entire time-line. We can conclude that fullerenol has cytotoxic effects on HepG2 by itself, but when the oxidative stress is too high the cytotoxic effects of fullerenol are overcome by its protective role as a strong antioxidant compound.     

Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver

Endotoxemia-induced hepatotoxicity is characterized by disturbed intracellular redox balance, excessive reactive oxygen species (ROS) generation inducing DNA, proteins and membrane lipid damages. In the present study, the protective effects of montelukast (MNT) against Escherichia coli lipopolysaccharides (LPS)-induced oxidative stress were investigated in rat liver. LPS (10 mg/kg, i.p.) was injected and the animals were sacrificed 6 h after LPS challenge. MNT (10 mg/kg) was administered orally for seven successive days before endotoxemia induction. Blood samples were withdrawn for assessing the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and levels of serum total bilirubin, total protein, tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). Livers were dissected out and used for histological examination or stored for the determination of malondialdehyde (MDA), protein carbonyl content (PCC), reduced glutathione (GSH) levels, enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO). Sepsis significantly increased ALT, AST, ALP, LDH, total bilirubin, TNF-α and IL-1β, MPO, MDA and PCC levels and decreased total protein, GSH and enzymatic antioxidants (CAT, SOD and GSH-Px). MNT decreased the markers of liver injury (AST, ALT, ALP, LDH, and total bilirubin), inflammatory biomarkers (TNF-alpha, IL-1β), MDA, PCC and MPO after LPS challenge. In conclusion, MNT abrogates LPS-induced markers of liver injury and suppresses the release of inflammatory and oxidative stress markers via its antioxidant properties and enhancement enzymatic antioxidant activities.     

Diagnostic efficiency of selected biochemical variables to predict the clinical outcome of exertional rhabdomyolysis in Egyptian draft horses

As little is known about redox status in horses with rhabdomyolysis, the present study was carried out to evaluate the diagnostic efficiency of oxidative stress markers as well as selected biochemical variables to predict the clinical outcome of exertional rhabdomyolysis (ER) in Egyptian draft horses. ER was tentatively diagnosed based on the competent case history and physical examination findings and confirmed by elevation of plasma creatine kinase (CK) levels. According to the clinical outcome, the diseased horses were categorized into two groups: survivors (n?=?21) and non-survivors (n?=?10). The analysis of receiver operating characteristic curve (ROC) showed high sensitivity and specificity of CK, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipid peroxides (LPO), malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and Vitamin C. Their cutoff points were >127,778?U/L, >16,100?U/L, >3,433?U/L, >1,294?U/L, >6.8?nmol/L, >14.0?μmol/L, >9.30?μmol/L, <0.62?mmol/L, <2.21?×?10³?IU/g Hb, <60.5?IU/g Hb, and <68.5?mg/dL, respectively. Of the tested variables, CK, LDH, AST, LPO, MDA, and vitamin C appear to have higher sensitivity (100%) and specificity (91%) to predict non-survivorship in examined horses. Our findings suggest that estimation of oxidative stress markers as well as CK, LDH, ALT, and AST not only have diagnostic significance in Egyptian horses with rhabdomyolysis but also can help predict clinical outcomes of such a clinical condition.     

再灌注前干预肥大细胞功能对大鼠肠缺血再灌注后早期肝损伤的影响

 目的：探讨肠缺血后再灌注前干预肥大细胞功能对SD大鼠继发肝脏损伤的影响及机制。方法：35只大鼠随机分成5组：假手术组（S组）、缺血再灌注组（IR组）、缺血再灌注＋色甘酸钠组（IR+C组）、缺血再灌注＋酮替芬组（IR+K组）和缺血再灌注＋compound 48/80 组（IR+CP组）。复制大鼠肠缺血再灌注模型,IR+C、IR+K和IR+CP组分别在再灌注前5 min经尾静脉给予相应药物,S和IR组给予等量生理盐水。再灌注4 h后处死大鼠,观察各组肝脏病理变化及评分,测定血清丙氨酸氨基转移酶（ALT）活性、天冬氨酸氨基转移酶（AST）活性和组胺含量,检测肝脏乳酸脱氢酶（LDH）活性、丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性和肿瘤坏死因子α（TNF-α）、白细胞介素8（IL-8）水平。结果：与S组相比,IR组肝脏病理损伤明显（P<0.05）,血清ALT、AST水平、组胺含量、肝LDH活性、MDA、TNF-α、IL-8水平升高,SOD活性减弱（P<0.05）。与IR组相比,IR+C和IR+K组肝脏损伤减轻,以上指标呈相反趋势（P<0.05）,IR+CP组则加重肝损伤及恶化检测结果（P<0.05）。结论：再灌注前抑制肥大细胞功能可以减轻肠缺血再灌注后早期肝脏损伤,其机制可能与组胺释放、氧化损伤和炎症反应有关。     

Protective effects and antioxidant mechanism of bamboo leaf flavonoids on hepatocytes injured by CCl4

The protective effects and antioxidant mechanisms of bamboo leaf flavonoids (BLFs) on hepatocytes injured by CCl₄ were studied by establishing models of hepatocyte damage induced by CCl₄ and detecting the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione peroxidase (GSH-Px), superoxide dismurase (SOD), malondialdehyde (MDA) content and liver glycogen content. The degree of lesions in liver tissues between model and dosage groups was observed through paraffin sections. Results showed that BLFs significantly inhibit CCl₄-induced liver injury. The ALT and AST activities as well as MDA contents of cells decreased significantly after treatment with BLFs. GSH-Px and SOD activities as well as liver glycogen contents remarkably increased in the flavonoids groups, which exhibited dose-dependent relationships (P < 0.05). The degree of lesions in liver tissues in the BLF groups was microscopically better than that in the model group. BLFs also significantly suppressed hepatocellular injury and death of apoptotic cells. Therefore, BLFs have remarkable protective effects on acute liver injury, which is related to its strong antioxidant capacity to reduce damage in the liver caused by oxidative stress and cell (NCTC-1469) apoptosis. The results of this study provide pharmacological evidence to support the clinical application of BLFs.     

Preliminary study on the protective effect of vitamin C on monosodium glutamate-induced hepatotoxicity in rats

Monosodium glutamate (MSG) is a food additive with a wide range of biological effects but its high dose and prolonged use can cause a toxic effect on the liver. Therefore, the present study was aimed at investigating the role of vitamin C in MSG-induced hepatotoxicity in rats. MSG was administered to rats (by gavage) at a dose of 6 mg/g body weight for 10 days to induce hepatotoxicity, and vitamin C at a dose of 500 mg/kg body weight was coadministered to evaluate its ameliorating effect by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum; superoxide dismutase (SOD) and catalase activities in liver fraction; lipid peroxidation; and liver weight. It was found that MSG significantly (P?<?0.05) induced lipid peroxidation (LPO), increased liver weight, and increased activity of SOD and catalase in the liver of animals. The activity of ALT and AST was also increased in the serum on MSG administration. Vitamin C (500 mg/kg) coadministered with MSG significantly reduced LPO and liver weight and decreased the hepatic activity of catalase, but the activity of SOD was not reduced significantly. Also, a significant reduction in ALT and AST activity was observed. MSG induced oxidative stress and hepatic toxicity in the experimental animals at a dose of 6 mg/g body weight. Vitamin C significantly reduced the oxidative stress and hepatic toxicity induced by MSG, thereby providing a protective effect against the MSG-induced hepatotoxicity. The protective effect is associated with decreased LPO and liver weight and decreased activities of catalase, ALT, and AST.     

对氧磷酶3基因过表达对急性中毒小鼠肝损伤的保护作用及机制

目的 探讨对氧磷酶3（PON3）对急性中毒肝损伤的保护作用及作用机制。 方法 将40只Balb/c小鼠随机分为4组,正常对照（NC）组、敌敌畏（DDVT）对照组、绿色荧光蛋白慢病毒（Lv-GFP）组和重组PON3慢病毒（Lv-PON3）组,每组10只。LV-GFP组和Lv-PON3组小鼠经尾静脉分别注射2×10⁷ TU的Lv-GFP、Lv-PON3慢病毒,3 d后腹腔注射敌敌畏（DDVT）溶液9 mg/kg,DDVT组只需腹腔注射同等剂量DDVT,NC组注射同等剂量生理盐水。各组于DDVT染毒后12 h麻醉处死10只小鼠取肝组织,ELISA法检测各组血清乙酰胆碱酯酶（AChE）、肝功能指标谷丙转氨酶（ALT）和谷草转氨酶（AST）和肝组织氧化应激指标丙二醛（MDA）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）,HE染色法观察肝组织形态学改变,Real-time PCR检测肝组织Kelch样环氧氯丙烷相关蛋白-1（Keap1）、血红蛋白加氧酶（HO-1）和转录因子NF-E2相关因子2（Nrf2） mRNA的表达。 结果 与NC组比较,DDVT组和Lv-GFP组肝组织MDA、ALT、AST水平,HO-1和Nrf2 mRNA表达量明显升高,AChE、CAT、SOD、GSH水平和Keap1 mRNA表达量均明显降低（P<0.05）。与DDVT组比较,Lv-PON3组肝组织MDA、ALT、AST水平,Keap1 mRNA表达量降低,AChE、CAT、SOD和GSH水平均明显著升高,HO-1和Nrf2 mRNA表达量显著上升（P<0.05）。正常对照组肝细胞结构清晰,未出现肝细胞坏死和脂肪病变的情况,DDVT组和Lv-GFP组出现肝细胞坏死和脂肪变性等病理改变,Lv-PON3组肝脏病变组织肝细胞坏死和脂肪变性细胞数有一定的减少。 结论 PON3可通过Keap1-Nrf2/HO-1途径缓解氧化应激反应,改善肝功能,对敌敌畏急性中毒小鼠肝损伤有一定的保护作用。     

小檗碱预防脂多糖性肝损伤的机制研究

目的： 观察小檗碱对脂多糖性肝损伤的防治效果及其作用机制。 方法： 将雄性昆明小鼠随机分成4组：① 对照组：用蒸馏水灌胃（0.01 mL/g），每天1次，共5 d，第5 d灌胃后1 h，腹腔注射生理盐水（0.02 mL/g）；②小檗碱组：用5 g/L中性硫酸小檗碱灌胃（0.01 mL/g），每天1次，共5 d，第5 d灌胃后1 h，腹腔注射生理盐水（0.02 mL/g）； ③ 脂多糖（LPS）组：除腹腔注射LPS（0.02 mL/g，28 mg/kg）外，其余处理同①；④小檗碱防治组：除腹腔注射LPS（0.02 mL/g，28 mg/kg）外，其余处理同②。腹腔注射后2 h和10 h去眼球取血，分别检测各组小鼠血清中TNF-α的含量以及丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的活性；另于腹腔注射后24 h取肝组织标本，观察各组小鼠肝脏的组织学和超微结构的变化,同时测定肝组织MDA的含量及SOD的活性。 结果： LPS组小鼠血清ALT、AST活性明显高于对照组（P＜0.01），而小檗碱防治组小鼠血清ALT和AST活性明显低于LPS组（P＜0.05）。腹腔注射LPS后2 h，LPS组小鼠血清中TNF-α含量明显高于小檗碱防治组。组织学检查发现，LPS组小鼠肝细胞水肿、变性、坏死，肝窦充血；电镜下可见，肝细胞核溶解、部分核膜不完整，线粒体肿胀、嵴消失。小檗碱防治组小鼠肝脏的病理变化明显轻于LPS组。此外，LPS组肝脏组织中MDA的含量明显高于对照组（P＜0.01），而小檗碱防治组肝脏组织中MDA的含量低于LPS组（P＜0.05），但小檗碱防治组肝组织中SOD活性与LPS组比较无显著差异。 结论： 小檗碱可以减轻LPS引起的肝脏损伤，其作用机制可能与其抑制LPS诱导的TNF-α释放，减少肝组织脂质过氧化和保护肝细胞线粒体有关。     

Protective effect of rapamycin against acrylamide-induced hepatotoxicity: The associations between autophagy,apoptosis, and necroptosis

Acrylamide (ACRL) was demonstrated to induce hepatotoxicity and programmed cell death (PCD). Rapamycin (RAPA)-induced autophagy had been reported to limit the progression of hepatocellular injury in experimental models. This research was designed to study two death pathways involved in ACRL-induced hepatotoxicity and the modulating effect of RAPA on the resulting hepatic injury. Thirty-six adult male rats were divided into three groups: control group, ACRL-treated group (20 mg kg/day), and the last group co-treated with ACRL plus RAPA (0.5 mg kg/day). Drugs were administered for 21 days via oral gavage. Blood samples were collected to assess alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Livers were dissected; parts were used for detection of superoxide dismutase (SOD) and malondialdehyde (MDA) tissue levels. Other parts were processed for hematoxylin and eosin, Masson's trichrome staining, immunostaining for microtubule-associated proteins 1A/1B light chain 3B (LC3), ubiquitin-binding protein (p62), caspase-3, and receptor-interacting protein kinase 1 (RIPK1). ACRL induced a significant elevation in ALT, AST, MDA levels, and reduction in the SOD level. ACRL also induced hepatocellular injury, fibrosis, and defective autophagy indicated by elevation of LC3 and p62 and increased p62/LC3 ratio. Moreover, it increased the apoptotic (caspase-3) and necroptotic (RIPK1) markers expression. RAPA significantly reduced liver enzymes, oxidative stress, fibrosis, and improved liver histology. Moreover, RAPA decreased p62/LC3 ratio indicated enhanced autophagy, and significantly reduced caspase-3 and RIPK1 expression. In conclusion, RAPA maintained autophagic activity which may save the hepatocytes from PCD and enhance cell viability.     

Evaluation of prophylactic and therapeutic effects of silymarin on mebendazole-induced hepatotoxicity in cats

The aim of this study was to determine the protective action of silymarin on mebendazole-induced hepatotoxicity in cats. Twenty five healthy cats were randomly allotted into five equal groups. Cats in group A were given mebendazole (single dose 200?mg?kg, p.o.); group B consisted of cats that received silymarin (single dose 30?mg?kg, p.o.) concurrent with mebendazole administration; groups C, D and E were treated as group B, but silymarin was administered 2, 12 and 24?h after mebendazole administration, respectively. The serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total and direct bilirubin were measured before mebendazole administration and 2, 12, 24 and 72?h later as indices of liver injury. A single oral administration of mebendazole significantly elevated serum concentrations of ALT, AST, ALP, LDH (in all cases), and total and direct bilirubin in one cat in group A, after 24?h (P?<?0.05). In groups B and C, levels of serum enzyme activities and total and direct bilirubin remained within normal values, but in group D, levels of serum enzyme activity (in four cases) were higher than normal values and total and direct bilirubin remained within the normal range. In group E, levels of serum enzyme activities (in all cats) and total and direct bilirubin (in one cat) were higher than normal values. In conclusion, silymarin can protect liver tissue against oxidative stress in cats with mebendazole intoxication particularly in the first 2?h after exposure.     

红景天苷对非酒精性脂肪性肝炎大鼠肝组织氧化应激的抑制作用

 目的：观察红景天苷（salidroside ,SDS）对大鼠非酒精性脂肪性肝炎（NASH）肝组织氧化应激的影响。方法：以高脂高胆固醇饮食14周诱导建立大鼠NASH模型,药物干预组在造模第8周末时给予SDS 300 mg·kg-1·d-1体重灌胃连续6周,在14周末检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇（TC）和甘油三酯（TG）,以及肝组织TC、TG、丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）含量的变化,ELISA检测8-异前列腺素F2α(8-iso-PGF2α)的水平变化, HE染色观察肝组织病理学变化,免疫组化观察8-羟基脱氧鸟苷酸（8-OHdG）表达的变化。结果：在14 周末, NASH模型组大鼠肝组织病理学检查显示肝组织呈中重度脂肪变性并同时伴有炎症细胞浸润;与正常对照组相比,NASH模型组大鼠血清ALT、AST、TG和TC,以及肝TG、TC和MDA的含量显著上升,而肝SOD和GSH的含量显著下降,8-iso-PGF2α的水平显著上升,免疫组化显示8-OHdG表达的阳性细胞数显著增多。与模型组相比,SDS药物干预组大鼠ALT、AST、TG、TC、MDA和8-iso-PGF2α的含量均显著下降,而肝SOD和GSH的含量显著上升,肝病理学变化得到显著改善,8-OHdG表达的阳性细胞数明显减少。结论：SDS对高脂高胆固醇饮食诱导的NASH有较好的抑制效果,其机制可能与SDS的抗氧化作用有关。     

蛇菰多糖降低实验性肝损伤大鼠肝脏BDNF和TrkB的表达

目的蛇菰多糖(BPS)对D-半乳糖(D-gal)所致实验性肝损伤大鼠的肝功能及肝组织内BDNF、TrkB蛋白和凋亡相关蛋白表达的影响。方法将大鼠随机分为对照组(control),D-gal组(皮下注射D-半乳糖200 mg/kg),BPS低(D-gal+BPS-L)、中(D-gal+BPS-M)、高(D-gal+BPS-H)剂量组,分别每天灌胃50、100和200 mg/kg BPS,共6周。心脏取血检测血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平;HE染色法观察肝组织形态;免疫组织化学染色检测BDNF和TrkB的定位;Western blot检测BDNF、TrkB、Bcl-2、caspase-3和Bax蛋白表达;ELISA测定肝组织内丙醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果与对照组相比,D-gal组肝细胞水肿、点状坏死;血清ALT和AST水平升高(P<0.05),SOD活性降低、MDA含量升高(P<0.05);Bax、caspase-3、BDNF、TrkB表达增加(P<0.05),Bcl-2表达降低(P<0.05);与D-gal组相比,BP...     

Protective effect of kombucha tea against acetaminophen-induced hepatotoxicity in mice: a biochemical and histopathological study

Acetaminophen overdose causes severe hepatotoxicity leading to liver failure in experimental animals and humans. This study was undertaken to evaluate the protective effect of kombucha tea (KT) against acetaminophen-induced hepatotoxicity. Forty male Balb/c mice were divided into four equal groups: (1) the control group, (2) KT-treated group, (3) acetaminophen-treated group, and (4) KT/acetaminophen-treated group. All mice in group 4 were given KT orally for 7?days before a single hepatotoxic dose of acetaminophen (1,000?mg/kg orally). Activities of liver marker enzymes in serum; aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP); and total protein (TP), albumin (ALB), and direct and total bilirubin levels were determined. Acetaminophen challenge caused significant increases in the levels of bilirubin and liver enzymes (AST, ALT, ALP, and LDH), while TP and ALB levels were reduced significantly. Histopathologic assessments showed that severe glycogen storage in hepatocytes, hepatocellular degeneration and necrosis, mononuclear cell infiltration in portal area, dilation of central veins, and capillarization also reduced in KT/acetaminophen group compared to acetaminophen-treated mice. In conclusion, these findings suggest that KT has protective effect on acetaminophen-induced hepatotoxicity.     

山丹黄参多糖对四氯化碳诱导的慢性肝损伤的保护作用

目的 探讨山丹黄参多糖对四氯化碳（CCl4）小鼠肝损伤的保护作用。方法 将40只小鼠分为正常对照组、实验对照组、山丹黄参多糖1～3组5个组,山丹黄参多糖1～3组分别连续灌胃浓度为12.5、25.0和37.5 g/L的山丹黄参多糖（共28 d,每天2次,每次 0.2ml）,正常对照组和实验对照组灌胃等量的生理盐水,灌胃多糖第3天起,实验对照组：山丹黄参多糖1、2、3组各组小鼠于下午灌胃 2 h后分别腹腔注射0.2％CCl4橄榄油溶液 0.2ml（每3天1次,共9次）,正常对照组腹腔注射等量的生理盐水。用光学显微镜观察肝组织的结构变化,用比色法检测血浆谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)和肝组织超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量的变化,用免疫组织化学法检测Caspase-3及Bax蛋白在肝组织表达的变化。 结果 实验对照组血浆ALT、AST和ALP含量显著升高（P<0.01）,肝组织SOD活力明显降低（P<0.01）,MDA含量显著升高（P<0.01）,肝组织结构不清,肝细胞炎性坏死,空泡化严重,Caspase-3蛋白和Bax蛋白阳性表达明显增强（P<0.01）。山丹黄参多糖各组血浆ALT、AST、ALP活性明显降低,肝组织SOD活力显著升高（P<0.01）,MDA含量明显下降（P<0.01）,肝索清晰,炎性坏死减少,肝细胞结构清晰,Caspase-3及Bax蛋白阳性表达明显减少（P<0.01）。结论 山丹黄参多糖可提高细胞抗氧化活性,具有抗炎、抗氧化、抑制细胞凋亡和保护肝细胞等作用,能有效减轻CCl4对肝组织的损伤,且在一定范围内呈剂量效应。     

Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological,Immunohistochemical, and Biochemical Study

Potassium bromate (KBrO₃) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO₃ mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO₃ induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO₃ orally twice weekly for 4 weeks and Group 4: received both KBrO₃ and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO₃ induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO₃. Anat Rec, 299:1256–1269, 2016. © 2016 Wiley Periodicals, Inc.     

Effect of Zingiber officinale on liver oxidative status and biochemical parameters in rats exposed to paraquat

Oxidative stress caused by reactive oxygen species is one of the major pathogenesis of important diseases of animals and human. Paraquat is widely used as herbicide. The toxicity of paraquat is through induction of oxidative processes in biological systems. Biochemically, this herbicide interferes with intracellular electron transfer system leading to the formation of superoxide anion. Zingiber officinale (ginger) is widely used as a spice and medical treatment for various diseases. The objective of this study was to assess the effect of different levels of ginger extract on antioxidant status and serum metabolites of rats. Sixty male albino Wistar rats were divided in six groups as follows: control (saline); ginger; paraquat; paraquat with 100, 200, and 400 ginger. After 30 days of treatment, the blood was collected by cardiac puncture. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), reduced glutathione (GSH), and lipid peroxidation were estimated. In paraquat-treated group, the serum levels of ALT, AST, and malondialdehyde (MDA) were markedly raised. Administration of ginger extract with paraquat reduced the serum levels of ALT, AST, and MDA. Hepatic SOD, CAT, GPx, GST, and GSH activities were significantly decreased in paraquat-treated group compared to those of control. However, concurrent administration of paraquat with all concentrations of ginger extract had the opposite effect, where it increased the hepatic SOD, CAT, GPx, GST, and GSH activities near to control. The present study demonstrates that administration of ginger extract to rats modulates the antioxidant enzymes and suggests a possible adaptive mechanism to counteract oxidative stress situation.     

Effects of erdosteine on acetaminophen-induced hepatotoxicity in rats

We investigated the effects of erdosteine on acetaminophen (APAP)-induced hepatotoxicity in rats. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), AST (aspartate aminotransferase), and ALT (alanine transaminase) activities, and malonyldialdehyde (MDA) and nitric oxide levels as oxidant/antioxidant biochemical parameters were investigated with light microscopic evaluation in adult female Wistar Albino rats. APAP administration produced a decrease in hepatic SOD, CAT, and GSH-Px activities, and coadministration of erdosteine (150 and 300 mg/kg) resulted in increases in the activities. MDA and NO levels increased in the APAP group, and erdosteine treatments prevented these increases. Significant elevations in serum AST and ALT levels were observed in the APAP group, and when erdosteine and APAP were coadministered, their serum levels were close to those in the control group. Light microscopic evaluation of livers showed that there were remarkable centrilobular (zone III) hepatic necrosis and mild to moderate sinusoidal congestion in the APAP group, whereas in the erdosteine group, cellular necrosis was minimal and the hepatocytes maintained a better morphology when compared to the APAP group. Erdosteine prevented APAP-induced liver injury and toxic side effects probably through the antioxidant and radical scavenging effects of erdosteine.     

抗衰老Klotho蛋白减轻大鼠乳鼠心肌细胞缺氧/复氧损伤

目的:观察抗衰老Klotho蛋白对大鼠乳鼠原代心肌细胞缺氧/复氧(H/R)损伤的作用并探讨其作用机制。方法:建立大鼠乳鼠心肌细胞H/R模型,并将心肌细胞分为正常对照组、H/R模型组和不同浓度(0.1μmol/L、1μmol/L和10μmol/L)Klotho作用H/R组。观察各组心肌细胞H/R前后搏动频率变化,利用MTT方法检测细胞存活率;测定各组心肌细胞H/R后LDH、CK、AST的漏出量及MDA含量、SOD活性;流式细胞术检测各组心肌细胞的凋亡率;real-time PCR检测各组心肌细胞中内质网应激标记及凋亡相关分子GRP78、CRT和CHOP和caspase-12 mRNA的表达情况;Western blot法检测心肌细胞内内质网应激凋亡蛋白CHOP和caspase-12蛋白表达及Akt磷酸化水平。结果:与正常对照组相比,H/R模型组中心肌细胞搏动频率和细胞存活率显著下降,细胞凋亡率显著升高(P0.05);LDH、CK、AST和MDA含量升高而SOD活性显著降低(P0.05);GRP78、CRT、CHOP和caspase-12 mRNA表达显著增高(P0.05);CHOP和caspase-12蛋白表达随之增高而Akt的磷酸化水平显著降低(P0.05)。与H/R模型组相比,抗衰老Klotho蛋白作用H/R心肌细胞后,心肌细胞搏动频率和细胞存活率显著升高,细胞凋亡率逐渐降低(P0.05),LDH、CK、AST和MDA含量下降而SOD活性显著增高(P0.05),GRP78、CRT、CHOP和caspase-12 mRNA的表达逐渐降低(P0.05),CHOP和caspase-12蛋白表达也随之降低,而Akt磷酸化水平显著增加(P0.05)。结论:抗衰老Klotho蛋白能够提升H/R损伤后心肌细胞的存活率,抑制细胞凋亡,通过抵抗氧化应激和过度内质网应激反应发挥作用,并与激活Akt磷酸化有关。     

Investigation of relationship between idiopathic hypercalciuria and urinary enzyme activities

In patients with uncomplicated idiopathic hypercalciuria renal function is normal except for increased renal calcium excretion. In this study, the level of fractional urinary enzyme excretion was assessed in relation to calciuria. Fourteen patients with a mean age of 5.8 +/- 0.8 years who had daily urinary calcium excretion more than 4 mg/kg and with otherwise normal renal function tests were included in the study. None of the patients manifested either renal calculus or nephrocalcinosis. Fourteen normal children with a mean age of 5.4 +/- 0.74 were included in the control group. The level of the urinary N-acetyl beta-D glucosaminidase (NAG) to creatinine ratio, fractional aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) excretion were not significantly different compared to the control group (p > 0.05). The patients were subdivided according to the type of hypercalciuria. The levels of NAG/creatinine ratio, fractional ALT, AST, ALP, LDH excretion were not significantly different in the absorptive type of calciuria group compared to the control group (p > 0.05). In conclusion, hypercalciuria during childhood which is 6.46 +/- 1.83 mg/kg/day is not related to the levels of NAG/creatinine ratio, fractional ALT, AST, ALP and LDH excretion in urine.     

重组人肝再生增强因子可逆转免疫损伤性肝纤维化

目的:了解重组人肝再生增强因子(hALR)抗免疫损伤性肝纤维化的活性。方法:建立人血白蛋白免疫损伤性大鼠肝纤维化模型。模型完成后予hALR 腹腔注射。观察肝纤维化大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)水平,肝组织胶原蛋白含量及肝脏病理学改变。结果:重组人肝再生增强因子(hALR)可降低肝纤维化大鼠的ALT、AST、LDH水平;肝组织胶原蛋白含量的测定表明hALR治疗组大鼠肝组织胶原含量明显低于模型组及阴性对照组;病理组织切片也发现hALR治疗组大鼠肝纤维化程度较模型组及阴性对照组明显减轻。结论:重组人肝再生增强因子(hALR)可逆转免疫损伤性大鼠肝纤维化。