Geniposide protects against acute alcohol-induced liver injury in mice via up-regulating the expression of the main antioxidant enzymes

Geniposide (GP) is one of main compounds in Gardenia jasminoides Ellis, with both medicinal and nutritional value. This study was designed to determine, for the first time, how GP from G. jasminoides protects against acute alcohol-induced liver injury, and the underlying mechanisms. Mice were orally administered alcohol (6.0 g/kg body mass) 2 h after intragastric administration of GP and bifendate, every day for 7 continuous days. Six hours after the alcohol was administered, levels of serum alanine/aspartate transaminase (ALT/AST), hepatic lipid peroxidation (LPO), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), copper- and zinc-containing superoxide dismutase (CuZn-SOD), and catalase (CAT), and mRNA expression of CuZn-SOD and CAT were assayed. The results demonstrated that GP (20.0, 40.0, or 80 mg/kg) significantly reversed the excessive, alcohol-induced elevation in both serum ALT/AST and hepatic LPO levels. Moreover, hepatic GSH, GST, GPx, CuZn-SOD, and CAT levels were all decreased in the alcohol-treated mice, whereas treatment with GP reversed these decreases. Further analysis indicated that hepatic mRNA expression of CuZn-SOD and CAT in the alcohol-treated mice was significantly down-regulated, whereas GP up-regulated such decreases. Taken together, this study shows that GP protects against acute alcohol-induced liver injury via up-regulating the expression of the main antioxidant enzymes, and thus ameliorates alcohol-induced oxidative stress injury in the liver.

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Gender-related difference in liver injury induced by Dioscorea bulbifera L. rhizome in mice

Human & Experimental Toxicology ◽

10.1177/0960327110389926 ◽

2010 ◽

Vol 30 (9) ◽

pp. 1333-1341 ◽

Cited By ~ 42

Author(s):

Junming Wang ◽

Qingning Liang ◽

Lili Ji ◽

Hai Liu ◽

Changhong Wang ◽

...

Keyword(s):

Liver Injury ◽

Chemical Compound ◽

Liver Lipid ◽

Dependent Manner ◽

Glutathione S Transferase ◽

Stress Injury ◽

Tissue Samples ◽

Female Mice ◽

Dioscorea Bulbifera ◽

Liver Lipid Peroxidation

The present study was undertaken to investigate the gender-related liver injury induced by Dioscorea bulbifera L. (DB), a traditional medicinal plant, in mice, and further explored its hepatotoxic chemical compound. Serum and liver tissue samples were collected at 0, 4, 8, 12 h, after mice were administrated orally with 640 mg/kg ethyl acetate extracts (EF) isolated from DB. After treatments, serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were both significantly elevated. Liver lipid peroxidation (LPO) level increased, while glutathione amounts, glutathione- S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities all decreased in the time-dependent manner. Further analysis demonstrated that ALT and AST activities in female mice were significantly lower than those in male. Meanwhile, liver glutathione amounts and CAT activity in female mice after giving EF for 12 h were both higher than those in male. Further, comparing the liver injury induced by Diosbulbin B isolated from DB with that induced by EF on the basis of chemical analysis for the amounts of Diosbulbin B in EF of DB, we found that Diosbulbin B could be the main hepatotoxic chemical compound in DB. Taken together, our results show that DB can induce gender-related liver oxidative stress injury in mice, and its main hepatotoxic chemical compound is Diosbulbin B, for the first time.

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Dietary Beta-Hydroxy Beta-Methyl Butyrate Supplementation Alleviates Liver Injury in Lipopolysaccharide-Challenged Piglets

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5546843 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Yehui Duan ◽

Bo Song ◽

Changbing Zheng ◽

Yinzhao Zhong ◽

Qiuping Guo ◽

...

Keyword(s):

Liver Injury ◽

Mrna Expression ◽

Basal Diet ◽

Control Group ◽

Protective Effects ◽

Ampk Signaling ◽

Lps Challenge ◽

Hepatic Energy Metabolism ◽

Serum Aspartate Aminotransferase ◽

Underlying Mechanisms

The current study was performed to investigate whether dietary β-hydroxy-β-methylbutyrate (HMB) could regulate liver injury in a lipopolysaccharide- (LPS-) challenged piglet model and to determine the mechanisms involved. Thirty piglets ( 21 ± 2 days old , 5.86 ± 0.18 kg body weight) were randomly divided into the control (a basal diet, saline injection), LPS (a basal diet), or LPS+HMB (a basal diet + 0.60% HMB-Ca) group. After 15 d of treatment with LPS and/or HMB, blood and liver samples were obtained. The results showed that in LPS-injected piglets, HMB supplementation ameliorated liver histomorphological abnormalities induced by LPS challenge. Compared to the control group, the activities of serum aspartate aminotransferase and alkaline phosphatase were increased in the LPS-injected piglets ( P < 0.05 ). The LPS challenge also downregulated the mRNA expression of L-PFK, ACO, L-CPT-1, ICDH β, and AMPKα1/2 and upregulated the mRNA expression of PCNA, caspase 3, TNF-α, TLR4, MyD88, NOD1, and NF-κB p65 ( P < 0.05 ). However, these adverse effects of the LPS challenge were reversed by HMB supplementation ( P < 0.05 ). These results indicate that HMB may exert protective effects against LPS-induced liver injury, and the underlying mechanisms might involve the improvement of hepatic energy metabolism via regulating AMPK signaling pathway and the reduction of liver inflammation via modulating TLR4 and NOD signaling pathways.

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Minocycline inhibits mTOR signaling activation and alleviates behavioral deficits in the Wistar rats with acute ischemia stroke

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319999200831153748 ◽

2020 ◽

Vol 19 ◽

Author(s):

Shengyuan Wang ◽

Chuanling Wang ◽

Lihua Wang ◽

Zhiyou Cai

Keyword(s):

Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Acute Ischemia ◽

Intragastric Administration ◽

Underlying Mechanisms ◽

Signaling Activation ◽

The Brain ◽

Minocycline Therapy

Background: Mammalian target of rapamycin (mTOR) has been evidenced as a multimodal therapy in the path-ophysiological process of acute ischemic stroke (AIS). However, the pathway that minocycline targets mTOR signaling is not fully defined in the AIS pathogenesis. This study is to aim at the effects of minocycline on the mTOR signaling in the AIS process and further discover the underlying mechanisms of minocycline involved in the following change of mTOR signaling-autophagy. Methods: Cerebral ischemia/reperfusion (CIR) rat animal models were established with the transient suture occlusion into middle cerebral artery. Minocycline (50mg/kg) was given by intragastric administration. The Morris water maze was used to test the cognitive function of animals. Immunohistochemistry and immunofluorescence were introduced for testing the lev-els of synaptophysin and PSD-95. Western blot was conducted for investigating the levels of mTOR, p-mTOR (Ser2448), p70S6, p-p70S6 (Thr389), eEF2k, p-eEF2k (Ser366), p-eIF4B (Ser406), LC3, p62, synaptophysin and PSD-95. Results: Minocycline prevents cognitive decline of the MCAO stroke rats. Minocycline limits the expression of p-mTOR (Ser2448) and the downstream targets of mTOR [p70S6, p-p70S6 (Thr389), eEF2k, p-eEF2k (Ser366) and p-eIF4B (Ser406)] (P<0.01), while minocycline has no influence on mTOR. LC3-II abundance and the LC3-II/I ratio were upregu-lated in the hippocampus of the MCAO stroke rats by the minocycline therapy (P<0.01). p62 was downregulated in the hippocampus from the MCAO stroke rats administrated with minocycline therapy(P<0.01). The levels of SYP and PSD-95 were up-regulated in the brain of the MCAO stroke rats administrated with minocycline therapy. Conclusion: Minocycline prevents cognitive deficits via inhibiting mTOR signaling and enhancing autophagy process, and promoting the expression of pre-and postsynaptic proteins (synaptophysin and PSD-95) in the brain of the MCAO stroke rats. The potential neuroprotective role of minocycline in the process of cerebral ischemia may be related to mitigating is-chemia-induced synapse injury via inhibiting activation of mTOR signaling.

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Therapeutic Potential of Biochanin-A Against Isoproterenol-Induced Myocardial Infarction in Rats

Cardiovascular & Hematological Agents in Medicinal Chemistry ◽

10.2174/1871525718666200206114304 ◽

2020 ◽

Vol 18 (1) ◽

pp. 31-36 ◽

Cited By ~ 3

Author(s):

Sangeethadevi Govindasami ◽

Veera Venkata Sathibabu Uddandrao ◽

Nivedha Raveendran ◽

Vadivukkarasi Sasikumar

Keyword(s):

Myocardial Infarction ◽

Antioxidant Enzymes ◽

Therapeutic Potential ◽

Biochanin A ◽

Glutathione S Transferase ◽

Serum Glutamic Oxaloacetic Transaminase ◽

Creatine Kinase Mb ◽

Male Wistar Rats ◽

Detoxifying Enzyme ◽

Cardioprotective Effects

Background: This study determined the effect of Biochanin A (BCA) on isoproterenol (ISO) induced Myocardial Infarction (MI) in male Wistar rats. Methods: Animals (weighing 150-180 g) were divided into four groups, with six animals in each group and pretreated with BCA (10mg/kg Body Weight [BW]) and ɑ-tocopherol (60mg/kg BW) for 30 days; and ISO (20mg/kg BW) was administrated subcutaneously on the 31st and 32nd day. Results: ISO-induced MI rats demonstrated the significant elevation of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, creatine kinase-MB and cardiac troponin; however, concomitant pretreatment with BCA protected the rats from cardiotoxicity caused by ISO. Activities of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase significantly reduced in the heart with ISO-induced MI. Pretreatment with BCA produced a marked reversal of these antioxidant enzymes related to MI-induced by ISO. Conclusion: In conclusion, this study suggested that BCA exerts cardioprotective effects through modulating lipid peroxidation, enhancing antioxidants, and detoxifying enzyme systems.

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Dietary exposure to methyl mercury chloride induces alterations in hematology, biochemical parameters, and mRNA expression of antioxidant enzymes and metallothionein in Nile tilapia

Environmental Science and Pollution Research ◽

10.1007/s11356-021-13014-5 ◽

2021 ◽

Author(s):

Rasha T. M. Alam ◽

Ehsan. H. Abu Zeid ◽

Bouthaina A. Khalifa ◽

Ahmed Hamed Arisha ◽

Rasha M. Reda

Keyword(s):

Antioxidant Enzymes ◽

Mrna Expression ◽

Methyl Mercury ◽

Biochemical Parameters ◽

Nile Tilapia ◽

Dietary Exposure ◽

Mercury Chloride

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Effect of Cross-Sex Hormonal Replacement on Antioxidant Enzymes in Rat Retroperitoneal Fat Adipocytes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/1527873 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Israel Pérez-Torres ◽

Verónica Guarner-Lans ◽

Alejandra Zúñiga-Muñoz ◽

Rodrigo Velázquez Espejel ◽

Alfredo Cabrera-Orefice ◽

...

Keyword(s):

Lipid Peroxidation ◽

Superoxide Dismutase ◽

Antioxidant Enzymes ◽

Glutathione Peroxidase ◽

Glutathione Reductase ◽

Enzymatic Activities ◽

Glutathione S Transferase ◽

Control Groups ◽

Intact Female ◽

Hormonal Replacement

We report the effect of cross-sex hormonal replacement on antioxidant enzymes from rat retroperitoneal fat adipocytes. Eight rats of each gender were assigned to each of the following groups: control groups were intact female or male (F and M, resp.). Experimental groups were ovariectomized F (OvxF), castrated M (CasM), OvxF plus testosterone (OvxF + T), and CasM plus estradiol (CasM + E2) groups. After sacrifice, retroperitoneal fat was dissected and processed for histology. Adipocytes were isolated and the following enzymatic activities were determined: Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). Also, glutathione (GSH) and lipid peroxidation (LPO) were measured. In OvxF, retroperitoneal fat increased and adipocytes were enlarged, while in CasM rats a decrease in retroperitoneal fat and small adipocytes are observed. The cross-sex hormonal replacement in F rats was associated with larger adipocytes and a further decreased activity of Cu-Zn SOD, CAT, GPx, GST, GR, and GSH, in addition to an increase in LPO. CasM + E2exhibited the opposite effects showing further activation antioxidant enzymes and decreases in LPO. In conclusion, E2deficiency favors an increase in retroperitoneal fat and large adipocytes. Cross-sex hormonal replacement in F rats aggravates the condition by inhibiting antioxidant enzymes.

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