Pregabalin, a GABA Analogue Protects against Carbon Tetrachloride-Induced Oxidative Stress and Liver Injury in Rats

2021 ◽  
Vol 11 ◽  
Author(s):  
Omar M.E. Abdel-Salam ◽  
Eman R. Youness ◽  
Fatma A. Morsy ◽  
Amany Ameen Sleem
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Dna Fragmentation ◽  
Liver Tissue ◽  
Paraoxonase 1 ◽  
Control Group ◽  
Acute Administration ◽  
Synthetic Analogue ◽  
Serum Aminotransferases

Pregabalin is a synthetic analogue of the neurotransmitter g-aminobutyric acid (GABA) and is used in the treatment of epilepsy and neuropathic pain. The aim of this study was to investigate the effect of pregabalin on toxic liver injury caused by the acute administration of carbon tetrachloride (CCl4). Rats were orally treated with CCl4 for two successive days either alone or along with intraperitoneal pregabalin at doses of 7 and 14 mg/kg. The control group received the vehicle (olive oil). Liver oxidative stress and damage were assessed by determining serum and/or liver tissue levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), DNA fragmentation, serum aminotransferases, paraoxonase-1 (PON-1), and hepatic histopathology. Results showed that CCl4 significantly (i) increased MDA and NO and decreased PON-1 in both serum and liver tissue, and (ii) decreased liver GSH content and induced marked hepatic DNA fragmentation. CCl4 treatment caused liver tissue injury as evidenced by significantly increased serum aminotransferases. In line with the above biochemical changes, the liver of CCl4-treated rats exhibited massive steatosis, vacuolar degeneration, cloudy swelling, and necrosis. In CCl4-treated rats, pregabalin given at the dose of 14 mg/kg significantly reduced the increments in MDA, NO, serum aminotransferases, and hepatic DNA fragmentation. Liver GSH was unaltered but hepatic and serum PON-1 activity increased after administering pregabalin which also improved, though not normalized, liver tissue histopathology. Collectively, these results suggest that the administration of pregabalin is associated with a reduction in experimental liver injury caused by CCl4. (First online: Apr 12, 2021)

scholarly journals Aloperine attenuates carbon tetrachloride-induced mouse hepatic injury via Nrf2/HO-1 pathway

2020 ◽  
Vol 19 (5) ◽  
pp. 983-988
Author(s):  
Rui Xiong ◽  
Shuzhong Shan ◽  
Xiaoming Wang ◽  
Xiaowen Zhang ◽  
Haixia Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Hepatic Injury ◽  
Acute Liver Injury ◽  
Control Group ◽  
Histopathological Analysis ◽  
Dependent Manner ◽  
Oxidative Stress Biomarkers ◽  
Cox 2

Purpose: To investigate whether aloperine pretreatment ameliorates acute liver injury in carbon tetrachloride (CCl4)-treated mice.Methods: Mice were injected with CCl4 and orally administered aloperine. Blood samples and liver tissues were used for histopathological and biochemical analyses, respectively. Protein expression levels were determined by western blotting.Results: Histopathological analysis indicate that aloperine pretreatment significantly alleviated CCl4- induced mouse hepatic injury. CCl4 treatment induced the upregulation of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine amino transferase (ALT), and total bilirubin (p < 0.05). However, these alterations were significantly inhibited by aloperine treatment. Moreover, aloperine pretreatment markedly decreased (p < 0.05) the CCl4-induced expression of oxidative stress biomarkers, including malondrialdeline (MDA), glutathione (GSH), catalase (CAT), and  superoxide dismutase (SOD). Compared to the control group, the protein levels of Nrf2, HO-1, iNOS, and COX-2 were significantly increased in the CCl4 group, while Nrf2 and HO-1 were upregulated. Furthermore, iNOS and COX-2 were downregulated in mouse liver in CCl4 + aloperine group compared to CCl4 group in a concentration-dependent manner (p < 0.05).Conclusion: Aloperine pretreatment appears to markedly upregulate Nrf2 and HO-1 and downregulate iNOS and COX-2 to suppress hepatic injury in mice. Thus, aloperine is a promising treatment for acute liver injury. Keywords: Hepatic injury, Aloperine, Oxidative stress, Nrf2/HO-1 pathway

The Effect of Immunosuppression on Selected Antioxidant Parameters in Patients with Graves’ Disease with Active Thyroid-Associated Orbitopathy

2020 ◽  
Author(s):  
Magdalena Londzin-Olesik ◽  
Beata Kos-Kudla ◽  
Jacek Karpe ◽  
Aleksandra Nowak ◽  
Mariusz Nowak
Keyword(s):  
Oxidative Stress ◽  
Clinical Symptoms ◽  
Immunosuppressive Treatment ◽  
Serum Vitamin ◽  
Serum Levels ◽  
Paraoxonase 1 ◽  
Control Group ◽  
Graves Disease ◽  
Methylprednisolone Treatment ◽  
Antioxidant Parameters

Abstract Background and Study Aims Thyroid-associated orbitopathy, the most common extrathyroidal manifestation of Graves’ disease, is an autoimmune inflammation of orbital soft tissue. We report the study assessing the effect of immunosuppressive treatment with methylprednisolone on selected antioxidant parameters in patients with Graves’ disease with active thyroid-associated orbitopathy. Patients and Methods Activity and serum levels of selected antioxidant parameters as well as lipid peroxidation products were determined in a group of 56 patients with active thyroid-associated orbitopathy at three time-points: at baseline, after the discontinuation of intravenous methylprednisolone treatment and at 3 months after the discontinuation of additional oral methylprednisolone treatment. A control group consisted of 20 healthy age- and sex-matched volunteers. Results We found an increased activity of superoxide dismutase and glutathione peroxidase and increased serum levels of uric acid, malondialdehyde and conjugated dienes, as well as a reduced activity of paraoxonase-1 and reduced serum vitamin C level in the study group at baseline. Systemic intravenous and oral methylprednisolone therapy led to normalization of activity and concentration of the most studied parameters. Conclusion Results of our study confirmed that oxidative stress is one of the factors involved in the pathogenesis of thyroid-associated orbitopathy and the methyloprednisolone treatment is effective in reducing both clinical symptoms and oxidative stress in patients with this disease.

scholarly journals Curcumin Decreased Oxidative Stress, Inhibited NF-κB Activation, and Improved Liver Pathology in Ethanol-Induced Liver Injury in Rats

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Suchittra Samuhasaneeto ◽  
Duangporn Thong-Ngam ◽  
Onanong Kulaputana ◽  
Doungsamon Suyasunanont ◽  
Naruemon Klaikeaw
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Early Stage ◽  
Control Group ◽  
Liver Pathology ◽  
Sprague Dawley ◽  
Hepatocyte Apoptosis ◽  
Sod Activity ◽  
Ethanol Group ◽  
Liver Histopathology

To study the mechanism of curcumin-attenuated inflammation and liver pathology in early stage of alcoholic liver disease, female Sprague-Dawley rats were divided into four groups and treated with ethanol or curcumin via an intragastric tube for 4 weeks. A control group treated with distilled water, and an ethanol group was treated with ethanol (7.5 g/kg bw). Treatment groups were fed with ethanol supplemented with curcumin (400 or 1 200 mg/kg bw). The liver histopathology in ethanol group revealed mild-to-moderate steatosis and mild necroinflammation. Hepatic MDA, hepatocyte apoptosis, and NF-κB activation increased significantly in ethanol-treated group when compared with control. Curcumin treatments resulted in improving of liver pathology, decreasing the elevation of hepatic MDA, and inhibition of NF-κB activation. The 400 mg/kg bw of curcumin treatment revealed only a trend of decreased hepatocyte apoptosis. However, the results of SOD activity, PPARγprotein expression showed no difference among the groups. In conclusion, curcumin improved liver histopathology in early stage of ethanol-induced liver injury by reduction of oxidative stress and inhibition of NF-κB activation.

Oxydative stress markers and cytokine levels in rosuvastatin-medicated hypercholesterolemia patients

2018 ◽  
Vol 44 (4) ◽  
pp. 530-538
Author(s):  
Aysun Çetin ◽  
İhsan Çetin ◽  
Semih Yılmaz ◽  
Ahmet Şen ◽  
Göktuğ Savaş ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Interleukin 1 ◽  
Paraoxonase 1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Phenotypic Effect ◽  
Necrosis Factor Alpha ◽  
Stress Markers ◽  
Tnf Α ◽  
Before And After

Abstract Background Limited research is available concerning the relationship between oxidative stress and inflammation parameters, and simultaneously the effects of rosuvastatin on these markers in patients with hypercholesterolemia. We aimed to investigate the connection between cytokines and oxidative stress markers in patients with hypercholesterolemia before and after rosuvastatin treatment. Methods The study consisted of 30 hypercholesterolemic patients diagnosed with routine laboratory tests and 30 healthy participants. The lipid parameters, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), paraoxonase-1 (PON1) and malondialdehyde (MDA) levels in controls and patients with hypercholesterolemia before and after 12-week treatment with rosuvastatin (10 mg/kg/day), were analyzed by means of enzyme-linked immunosorbent assay. Results It was found that a 12-week cure with rosuvastatin resulted in substantial reductions in IL-1β, IL-6 and TNF-α and MDA levels as in rising activities of PON1 in patients with hypercholesterolemia. Before treatment, the PON1 levels were significantly negatively correlated with TNF-α and IL-6 in control group, while it was positively correlated with TNF-α in patients. Conclusion Our outcomes provide evidence of protected effect of rosuvastatin for inflammation and oxidative damage. It will be of great interest to determine whether the correlation between PON1 and cytokines has any phenotypic effect on PON1.

scholarly journals Pemberian Ekstrak Floret Pisang Raja (Musa x paradisiaca) Mencegah Penurunan Kadar Superoksida Dismutase (SOD) pada Hati Mencit (Mus musculus) BALB/c dengan Aktivitas Fisik Berlebih

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Okky Irtanto ◽  
Alex Pangkahila ◽  
IGM Aman
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Mus Musculus ◽  
Liver Tissue ◽  
Day Treatment ◽  
Control Group ◽  
P Value ◽  
Control Group Design ◽  
Group Design ◽  
Post Test

Abstract: Overtraining accelerates aging due to the excessive production of free radicals that can cause oxidative stress. Banana floret extract contains bioactive compounds with antioxidant capacity which can increase the body's defence to deal with the oxidative stress by increasing the level of superoxide dismutase (SOD). This study was aimed to prove that the banana (Musa x paradisiaca) floret extract could prevent the decrease of superoxide dismutase (SOD) levels in overtraining-induced mice (Mus musculus) BALB/c liver. This was a true experimental study with the post-test only control group design. Subjects were 36 male mice (Mus musculus), BALB/c strain, 12 weeks old, weighing 20-22 g, which were divided into two groups with 18 mice each. The control group (P0) was treated with a placebo of 1 ml aquadest and overtrained for 14 days meanwhile the treatment group (P1) was treated with banana (Musa x paradisiaca) floret extract of 400 mg/kgBW/day and overtrained for 14 days. The results showed that after 14-day treatment, the mean SOD level in the liver tissue of the P0 group was 568.82±9.558 U/mg protein whereas in the P1 group was 588.37±10.629 U/mg protein (P < 0.01). The t-independent test showed a t value of -5.804 and a P value of 0.000 which indicated that after treatment, the levels of SOD in liver tissue of both groups were significantly different. Conclusion: Banana (Musa x paradisiaca) floret extract could prevent the decrease of superoxide dismutase (SOD) levels in the liver tissue of overtraining-induced mice (Mus musculus) BALB/c.Keywords: banana floret, SOD, liver, overtrainingAbstrak: Aktivitas fisik berlebih mempercepat penuaan karena meningkatkan produksi radikal bebas yang dapat menyebabkan stres oksidatif. Ekstrak floret pisang mengandung senyawa bioaktif dengan kapasitas antioksidan yang dapat meningkatkan pertahanan tubuh dalam menghadapi stres oksidatif melalui peningkatan kadar superoksida dismutase (SOD). Penelitian ini bertujuan untuk membuktikan bahwa pemberian ekstrak floret pisang raja (Musa x paradisiaca) dapat mencegah penurunan kadar SOD pada hati mencit (Mus musculus) BALB/c dengan aktivitas fisik berlebih. Jenis penelitian ialah eksperimental murni dengan post test only control group design. Subjek penelitian ialah 36 ekor mencit (Mus Musculus) BALB/c, jantan, berumur 12 minggu, berat badan 20-22 gr, yang dibagi menjadi dua kelompok masing-masing berjumlah 18 ekor mencit. Kelompok kontrol (P0) diberikan plasebo berupa aquadest sebanyak 1 ml dengan aktivitas fisik berlebih selama 14 hari, dan kelompok perlakuan (P1) diberikan ekstrak floret pisang raja (Musa x paradisiaca) dosis 400 mg/kgBB mencit per hari dicampur aquadest hingga 1 ml dengan aktivitas fisik berlebih selama 14 hari. Hasil penelitian menunjukkan rerata kadar SOD jaringan hati pada kelompok kontrol (P0) sesudah perlakuan (post-test) ialah 568,82±9,558 U/mg protein, sedangkan pada kelompok perlakuan (P1) ialah 588,37± 10,629 U/mg protein. Analisis kemaknaan dengan T-Independent mendapatkan nilai t= -5,804 dan nilai P = 0,000 yang menunjukkan bahwa sesudah perlakuan (post-test), kadar SOD jaringan hati pada kedua kelompok berbeda sangat bermakna. Simpulan: Ekstrak floret pisang raja (Musa x paradisiaca) dapat mencegah penurunan kadar SOD pada hati mencit (Mus musculus) BALB/c dengan aktivitas fisik berlebih.Kata kunci: floret pisang raja, SOD, hati, aktivitas fisik berlebih

scholarly journals A Preliminary Study on the Effect of Hydrogen Gas on Alleviating Early CCl4-Induced Chronic Liver Injury in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1933
Author(s):  
Jianwei Wang ◽  
Quancheng Cheng ◽  
Jinyu Fang ◽  
Huiru Ding ◽  
Huaicun Liu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Tissue ◽  
Uncoupling Protein ◽  
Liver Cells ◽  
Hydrogen Gas ◽  
Chronic Liver ◽  
Control Group ◽  
Protective Mechanism ◽  
Chronic Liver Injury ◽  
Ucp2 Expression

As a small-molecule reductant substance, hydrogen gas has an obvious antioxidant function. It can selectively neutralize hydroxyl radicals (•OH) and peroxynitrite (ONOO•) in cells, reducing oxidative stress damage. The purpose of this study was to investigate the effect of hydrogen gas (3%) on early chronic liver injury (CLI) induced by CCl4 and to preliminarily explore the protective mechanism of hydrogen gas on hepatocytes by observing the expression of uncoupling protein 2 (UCP2) in liver tissue. Here, 32 rats were divided into four groups: the control group, CCl4 group, H2 (hydrogen gas) group, and CCl4 + H2 group. The effect of hydrogen gas on early CLI was observed by serological tests, ELISA, hematoxylin and eosin staining, and oil red O staining. Immunohistochemical staining and Western blotting were used to observe the expression of UCP2 in liver tissues. We found that CCl4 can induce significant steatosis in hepatocytes. When the hydrogen gas was inhaled, hepatocyte steatosis was reduced, and the UCP2 expression level in liver tissue was increased. These results suggest that hydrogen gas might upregulate UCP2 expression levels, reduce the generation of intracellular oxygen free radicals, affect lipid metabolism in liver cells, and play a protective role in liver cells.

scholarly journals Hydroethanolic Extract of Defatted Buchholzia coriacea Seeds Alleviates Tamoxifen-Induced Hepatic Triglyceride Accumulation, Inflammation and Oxidative Distress in Rat

Medicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Ayokanmi Ore ◽  
Abideen Idowu Adeogun ◽  
Oluseyi Adeboye Akinloye
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Liver Injury ◽  
Hepatic Function ◽  
Protein Carbonyls ◽  
Control Group ◽  
Hepatic Triglyceride ◽  
Triglyceride Accumulation ◽  
Group I ◽  
Hydroethanolic Extract

Background: Tamoxifen (TMX) has proven to be effective in the prevention and treatment of breast cancer. However, long-term use of TMX is associated with hepatic steatosis, oxidative liver injury and hepatocarcinoma. Buchholzia coriacea seeds (BCS) have been widely applied in traditional medicine due to their nutritional and therapeutic potentials. This study investigates the protective effect of hydroethanolic extract of (defatted) B. coriacea seeds (HEBCS) against TMX–induced hepatotoxicity in rats. Methods: Thirty-six (36) male albino rats were divided into six groups (n = 6/group). Group I served as control. Group II received 50 mg/kg/day TMX orally (p.o.) (TMX) for 21 days, group III received TMX plus 125 mg/kg/d HEBCS p.o. (HEBCS 125) for 21 days, group IV received TMX plus 250 mg/kg/d HEBCS p.o. (HEBCS 250) for 21 days and rats in group V and VI received HEBCS 125 and HEBCS 250 respectively for 21 days. Results: Compared with the control, TMX caused a significant increase (p < 0.05) in serum hepatic function biomarkers: alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase by 57%, 60% and 68% respectively. TMX also caused a significant increase in hepatic triglycerides level by 166% when compared with control and a significant decrease in serum HDL-cholesterol level by 37%. Compared with control, hepatic marker of inflammation, tumour necrosis factor alpha (TNF-α) increased significantly by 220%, coupled with significant increase in expression of interleukin 6 and cyclooxygenase 2. There was also significant increase in levels of Biomarkers of oxidative stress, nitric oxide, malondialdehyde and protein carbonyls in the TMX group by 89%, 175% and 114% respectively when compared with the control. Hepatic antioxidants, reduced glutathione (GSH) level and activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) decreased significantly in the TMX group by 35%, 67%, 41%, 59% and 53% respectively when compared with the control. However, HEBCS at 250 mg/kg significantly protected against TMX–induced hepatotoxicity by decreasing hepatic triglyceride content, serum hepatic function biomarkers, hepatic inflammation and oxidative stress with significant improvement in hepatic antioxidant system. Histopathological findings show that HEBCS alleviate TMX–induced hepatocyte ballooning. Conclusions: Current data suggest that HEBCS protected against TMX–induced hepatotoxicity in rats. HEBCS may be useful in managing TMX–induced toxicities in breast cancer patients. It may also be helpful against other forms of liver injury involving steatosis, inflammation, free radicals, and oxidative damage.

scholarly journals Hepatoprotective effects of hydroethanolic extracts of Crocus sativus tepals, stigmas and leaves on carbon tetrachloride induced acute liver injury in rats

2021 ◽  
Vol 25 (2) ◽  
pp. 178-188
Author(s):  
Sabir Ouahhoud ◽  
◽  
Ilham Touiss ◽  
Amine Khoulati ◽  
Iliass Lahmass ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Total Bilirubin ◽  
Liver Weight ◽  
Crocus Sativus ◽  
Male Rats ◽  
Control Group ◽  
Distilled Water ◽  
Relative Liver Weight ◽  
Hepatoprotective Effects

Introduction: The present study investigated the hepatoprotective effects of stigmas, tepals and leaves of Crocus sativus on carbon tetrachloride (CCL4) induced liver injury in rats. Methods: Hydroethanolic extracts of Crocus sativus (stigmas, tepals and leaves) were administrated daily for 14 days by oral gavage. In the present study, 30 male rats divided into five groups were treated as 1: normal rats gavaged with distilled water; 2: intoxicated rats gavaged with distilled water and injected with CCL4; 3: rats treated with stigmas extract and injected with CCL4; 4: rats treated with tepal extract and injected with CCL4; 5: rats treated with leaf extract and injected with CCL4. Bodyweight and the relative liver weight were determined. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total cholesterol, triglycerides, bilirubin direct and total, total protein, albumin, urea and creatinine measured in plasma. Malondialdehyde (MDA) was quantified in liver homogenate. Results: The experimental data showed that the stigmas and tepals extracts significantly prevented weight body loss and improved the relative liver weight. They significantly protected against elevation of ALT, AST, direct bilirubin, total bilirubin, LDH, ALP, creatinine and MDA. Also, they enhanced significantly total proteins and albumin compared to the CCL4 control group. Moreover, leaves reduced ALT, AST, total bilirubin, LDH and MDA significantly. Conclusion: In conclusion, these results suggest that tepals, stigmas, and leaves extracts of Crocus sativus have hepatoprotective effects on CCL4 induced liver injury in rats.

scholarly journals Pharmacoprophylaxis of liver diseases: creating a new hepatoprotector

2020 ◽  
Vol 17 ◽  
pp. 00061
Author(s):  
Svetlana Zykova ◽  
Sergey Shurov ◽  
Aleksey Savinkov ◽  
Nino Gugushvili ◽  
Vladimir Talismanov
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Toxic Effect ◽  
Alanine Aminotransferase ◽  
Liver Diseases ◽  
Hepatoprotective Activity ◽  
Control Group ◽  
Biochemical Indicators ◽  
Intact Group ◽  
Biochemical Studies

The article presents a study of the hepatoprotective activity of a tricyclic heterocycle, which refers to 5, 6, 7, 8-tetrahydroquinolines. The effect of 8, 8-dimethyl-5-p-tolyl-8, 9-dihydro-2H-pyrido [4, 3, 2-de] cinnolin-3 (7H) was studied on rats under the influence of the model of toxic hepatosis induced by carbon tetrachloride to find out the indicators of peroxidation and biochemical indicators. Biochemical studies have shown that modelling toxic fat hepatosis caused by the inception of carbon tetrachloride to rats increased the activity of alanine aminotransferase by 2.5 times more compared with the intact group, indicating the development of oxidative stress induced by the treatment of pyrido [4, 3, 2] Cinnol I that reduced the toxic effect of CTC by 79.9 %. Mexidol had a less pronounced hepatoprotective effect: the activity of Alanine aminotransferase on animals of the second group was lower by 29.2 % than on rats from the control group. Thus, a new compound with hepatoprotective activity has been developed and studied.

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