The 5-HT1A Agonist Buspirone Decreases Liver Oxidative Stress and Exerts Protective Effect Against CCl4– Toxicity

We aimed to study the effect of buspirone, an anxiolytic drug and 5-HT1A agonist on liver injury induced by carbon tetrachloride (CCl4) in rats. Rats were orally treated with CCl4 (2.8 mL/kg in olive oil) along with buspirone at 10, 20 or 30 mg/kg once daily starting with CCl4 and for one week thereafter. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities were determined in the serum. Markers of oxidative stress: lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH), nitric oxide (nitrite/nitrate) levels were measured in the liver. Moreover, paraoxonase 1 activity was determined in the liver and serum. The administration of CCl4 led to significant increases in serum ALT, AST, and ALP activities. Results showed that there were significantly increased hepatic MDA, nitrite and decreased GSH levels. PON1 activity decreased both in the liver and serum, respectively. The immunohistochemical investigations using anti-caspase-3 antibody revealed that CCl4 caused apoptosis to many hepatocytes. DNA studies showed that CCl4 caused hypoploidy in hepatocytes. Rats treated with 20-30 mg/kg buspirone showed significant decrease in serum ALT and AST by 19.5-34.3% and 24.2-31.4%, respectively. Serum ALP decreased by 21.7% after 30 mg/kg buspirone. In the liver, the higher dose of the drug resulted in decreased MDA (by 15.8%), decreased nitric oxide (17.4%) and increased GSH (by 20.1%). Significantly increased serum PON1 activity by 43.9-53.5% was observed after treatment with 20-30 mg/kg buspirone. On histopathologic examination of liver sections, there was mild protective effect for the drug at 30 mg/kg. Sections stained with anti- caspase- 3 confirmed the results obtained from histopathological examination. Moreover, buspirone given at 30 mg/kg resulted in an increase in % of cells containing normal values of DNA. These results indicate that buspirone decreases liver oxidative stress and exerts protective effect against CCl4- toxicity. The study thus indicates more beneficial effects of buspirone as an anxiolytic drug and that the drug could be used safely in patients with liver disease.

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The beneficial effects of l-cysteine on brain antioxidants of rats affected by sodium valproate

Human & Experimental Toxicology ◽

10.1177/0960327117695634 ◽

2017 ◽

Vol 36 (11) ◽

pp. 1212-1221 ◽

Cited By ~ 3

Author(s):

RZ Hamza ◽

NS El-Shenawy

Keyword(s):

Oxidative Stress ◽

Cerebral Cortex ◽

Protective Effect ◽

Brain Tissue ◽

Sodium Valproate ◽

Histopathological Examination ◽

Control Group ◽

High Dose ◽

Beneficial Effects ◽

The Brain

Oxidative stress caused by sodium valproate (SV) is known to play a key role in the pathogenesis of brain tissue. The present study was designed to evaluate the protective effect of l-cysteine (LC) on the antioxidants of brain tissue of rats. The animals were divided into six groups: control group 1 was treated with saline as vehicle, groups 2 and 3 were treated with low and high doses of SV (100 and 500 mg/kg, respectively), group 4 was treated with LC (100 mg/kg), and groups 5 and 6 were treated with low-dose SV + LC and high-dose SV + LC, respectively. All the groups were treated orally by gastric tube for 30 successive days. Some antioxidant parameters were determined. Brain tissue (cerebral cortex) of SV-treated animals showed an increase in lipid peroxidation (LPO) and reduction in activity of enzymatic antioxidant and total antioxidant levels. Histopathological examination of cerebral cortex of SV rats showed astrocytic swelling, inflammation, and necrosis. After 4 weeks of the combination treatment of SV and LC daily, results showed significant improvement in the activity of cathepsin marker enzymes and restored the structure of the brain. LC was able to ameliorate oxidative stress deficits observed in SV rats. LC decreased LPO level and was also able to restore the activity of antioxidant enzymes as well as structural deficits observed in the brain of SV animals. The protective effect of LC in SV-treated rats is mediated through attenuation of oxidative stress, suggesting a therapeutic role for LC in individuals treated with SV.

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Abstract 15999: The Divergent Effects of Exercise Training After Myocardial Infarction or Pressure Overload Depend Critically on Endothelial Nitric Oxide Synthase

Circulation ◽

10.1161/circ.130.suppl_2.15999 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Yanti Octavia ◽

Elza v Deel ◽

Monique d Waard ◽

Martine d Boer ◽

An Moens ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Exercise Training ◽

Endothelial Nitric Oxide Synthase ◽

Pressure Overload ◽

Beneficial Effects ◽

Enhanced Chemiluminescence ◽

Enos Uncoupling ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

AIMS: Beneficial effects of aerobic exercise training are widely recognized. However, previously we discovered that the positive effects of exercise depend on the underlying cause of cardiac failure. Here we tested the hypothesis that endothelial nitric oxide synthase (eNOS) dependent regulation of the balance between nitric oxide and superoxide (O2•-) is critically involved in determining the effects of exercise. METHODS: Mice were exposed to 8 weeks of voluntary wheel running exercise training (EX) or sedentary housing (SED) immediately following myocardial infarction (MI), pressure overload from a transverse aortic constriction (TAC), or sham (SH) surgery. Subsequently, left ventricular (LV) ejection fraction (EF) was measured by echocardiography and Picrosirius Red staining was performed to measure collagen content. Additionally, total and NOS-dependent LV O2•- were measured using lucigenin-enhanced chemiluminescence without or with NOS inhibitor, L-NAME. eNOS uncoupling was evaluated by determining eNOS monomer dimer protein ratio and peroxynitrite (ONOO-) levels were measured through luminol-enhanced chemiluminescence. RESULTS: Cardiac dysfunction and fibrosis were ameliorated by exercise in MI but not in TAC mice (Table 1). MI and TAC both increased LV O2•- levels. Strikingly, EX diminished O2•- generation in MI, but exacerbated O2•- generation in TAC (Table 1). Furthermore, the EX-induced increase in O2•- levels in TAC were largely NOS-dependent. Accordingly, MI and TAC-induced eNOS uncoupling was normalized by EX in MI but aggravated in TAC mice (Table 1). Similarly, increased ONOO- levels following MI and TAC were diminished by EX in MI, but exacerbated by EX in TAC (Table 1). CONCLUSIONS: EX reduces eNOS-mediated cardiac oxidative stress in MI. In contrast, beneficial effects of EX are lacking in cardiac pressure-overload following TAC, due to EX-induced aggravation of ONOO- formation, eNOS uncoupling and concomitant oxidative stress.

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Sitagliptin-Dependent Differences in the Intensity of Oxidative Stress in Rat Livers Subjected to Ischemia and Reperfusion

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/2738605 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Małgorzata Trocha ◽

Małgorzata Krzystek-Korpacka ◽

Anna Merwid-Ląd ◽

Beata Nowak ◽

Małgorzata Pieśniewska ◽

...

Keyword(s):

Oxidative Stress ◽

Rat Liver ◽

Ischemia Reperfusion ◽

Antioxidant Properties ◽

Thiobarbituric Acid ◽

Treated Group ◽

Paraoxonase 1 ◽

Pon1 Activity ◽

Tbars Level ◽

Rat Livers

Purpose. Ischemia/reperfusion (IR) is the main cause of liver damage after transplantation. We evaluated the effect of sitagliptin (STG) on oxidative stress parameters in the rat liver under IR. Methods. Rats were treated with STG (5 mg/kg) (S and SIR) or saline solution (C and CIR). Livers from CIR and SIR were subjected to ischemia (60 min) and reperfusion (24 h). During reperfusion, aminotransferases (ALT and AST) were determined in blood samples. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), paraoxonase-1 (PON1), glutathione peroxidase (GPx), and the mRNA expression of SOD1 were determined in liver homogenates after reperfusion. Different regions of livers were also histologically evaluated. Results. The PON1 activity was higher, and the TBARS level was lower in SIR than in CIR. There was an inverse relationship between TBARS and PON1 levels in the whole cohort. The GPx activity was lower in ischemic than in nonischemic groups regardless of the STG treatment. In SIR, the SOD1 activity was higher compared to that in CIR. In S, the expression of SOD1 mRNA was the highest of all examined groups and positively correlated with the SOD1 activity in the whole animal cohort. During IR aminotransferases, the activity in the drug-treated group was lower in all examined points of time. In drug-treated groups, the percentage of steatosis was higher than that in nontreated groups regardless of IR. Conclusions. The protective effect of STG on the rat liver, especially its antioxidant properties, was revealed under IR conditions.

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P59. Protective effect of nitric oxide against arsenic-induced oxidative stress in rice

Nitric Oxide ◽

10.1016/j.niox.2008.06.156 ◽

2008 ◽

Vol 19 ◽

pp. 56

Author(s):

Harminder Pal Singh ◽

Shalinder Kaur ◽

Daizy Rani Batish ◽

Ravinder K Kohli

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Protective Effect

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Protective effect of adenosine triphosphate against sunitinib-related skin damage in rats

Human & Experimental Toxicology ◽

10.1177/0960327120940365 ◽

2020 ◽

Vol 39 (12) ◽

pp. 1737-1746

Author(s):

N Yıldırım ◽

A Karatas ◽

M Cengiz ◽

E Onalan ◽

GN Yazıcı ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Adenosine Triphosphate ◽

Histopathological Examination ◽

Total Antioxidant Status ◽

Stress Index ◽

The Sun ◽

Skin Damage ◽

Cutaneous Side Effects ◽

Total Antioxidant

Cutaneous side effects associated with sunitinib use are a major problem in patients receiving cancer treatment. The aim of this study was to investigate the protective effect of adenosine triphosphate (ATP) against possible skin damage resulting from sunitinib use in rats. Thirty Albino Winstar rats were divided into the following three groups: healthy controls (HCs, n = 10), sunitinib (SUN, n = 10), and sunitinib + ATP (SAT, n = 10). ATP was injected intraperitoneally at a dose of 2 mg/kg. One hour subsequent to the administration of ATP and 0.9% NaCl, the SAT and SUN groups were orally administered a dose of 25 mg/kg sunitinib to the stomach. Macroscopic evaluation of the skin indicated lower levels of skin damage in the SAT group than in the SUN group. As an indicator of oxidative stress, malondialdehyde (MDA), total oxidant status (TOS), and oxidative stress index (OSI) levels were significantly higher in the SUN group than in the HC group, while total glutathione (tGSH) and total antioxidant status (TAS) levels were significantly lower. However, MDA, TOS, and OSI levels were significantly lower in the SAT group than in the SUN group, while tGSH and TAS levels were significantly higher. Histopathological examination revealed keratin plugs with edema, vasopathology, and inflammatory cell infiltration in the SUN group. The SAT group showed less necrotic epithelium, keratin plugs, edema, and vasopathology than the SUN group. ATP can be effective in preventing skin damage caused by sunitinib use by reducing oxidative stress.

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Evaluation of the Potential Cardioprotective Activity of Some Saudi Plants against Doxorubicin Toxicity

Zeitschrift für Naturforschung C ◽

10.1515/znc-2012-5-609 ◽

2012 ◽

Vol 67 (5-6) ◽

pp. 297-307 ◽

Cited By ~ 6

Author(s):

Osama M. Ashour ◽

Ashraf B. Abdel-Naim ◽

Hossam M. Abdallah ◽

Ayman A. Nagy ◽

Ahmed M. Mohamadin ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activities ◽

Histopathological Examination ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Serum Markers ◽

Protective Effects ◽

Medicinal Uses ◽

Cordia Myxa

Doxorubicin (DOX) is an anthracycline antibiotic widely used as a chemotherapeutic agent in the treatment of several tumours. However, its cardiac toxicity limits its use at maximum therapeutic doses. Most studies implicated increased oxidative stress as the major determinant of DOX cardiotoxicity. The local Saudi flora is very rich in a variety of plants of quite known folkloric or traditional medicinal uses. Tribulus macropterus Boiss., Olea europaea L. subsp. africana (Mill.) P. S. Green, Tamarix aphylla (L.) H. Karst., Cynomorium coccineum L., Cordia myxa L., Calligonum comosum L’ Hér, and Withania somnifera (L.) Dunal are Saudi plants known to have antioxidant activities. The aim of the current study was to explore the potential protective effects of methanolic extracts of these seven Saudi plants against DOX-induced cardiotoxicity in rats. Two plants showed promising cardioprotective potential in the order Calligonum comosum > Cordia myxa. The two plant extracts showed potent in vitro radical scavenging and antioxidant properties. They significantly protected against DOX-induced alterations in cardiac oxidative stress markers (GSH and MDA) and cardiac serum markers (CK-MB and LDH activities). Additionally, histopathological examination indicated a protection against DOX-induced cardiotoxicity. In conclusion, C. comosum and C. myxa exerted protective activity against DOX-induced cardiotoxicity, which is, at least partly, due to their antioxidant effect

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Protective Effect of Standardized Extract ofGinkgo bilobaagainst Cisplatin-Induced Nephrotoxicity

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/846126 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Jie Song ◽

Dan Liu ◽

Liang Feng ◽

Zhenhai Zhang ◽

Xiaobin Jia ◽

...

Keyword(s):

Oxidative Stress ◽

Caspase 3 ◽

Porcine Kidney ◽

Beneficial Effects ◽

Protein Levels ◽

Ros Accumulation ◽

Proximal Tubular ◽

Antitumor Compound ◽

Caspase Cascade

Cisplatin (CDDP) is a potent antitumor compound widely used with a notably side effect of nephrotoxicity inducing oxidative stress and apoptosis in kidneys. Standardized extract from the leaves of theGinkgo bilobatrees, labeled EGb761 (EGb), has been available on the market for its beneficial effects. The purpose of this study was to investigate the ability of EGb to prevent the nephrotoxic effect of CDDP and the mechanisms involved. Our results showed that EGb treatment restored the levels of creatinine, BUN, MDA, NO, SOD, CAT, GPx, and GSSG/GSH ratio in kidneys after CDDP injection. EGb also exhibited a tendency to decrease the elevated NF-κB translocation and caspase-3 protein levels in CDDP-treated kidneys. We further used a porcine kidney proximal tubular epithelial (LLC-PK1) cell line, finding that EGb accordingly inhibited ROS accumulation and iNOS increase induced by CDDPin vitro. EGb also attenuated IκB degradation and p65 NF-κB phosphorylation triggered by CDDP in LLC-PK1 cells. But EGb failed to influence CDDP-stimulated caspase cascade. These findings suggested that EGb’s renoprotective effect might be mediated by not only its well-known antioxidant activity but also the anti-inflammatory activity.

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