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      Indigofera oblongifolia Prevents Lead Acetate-Induced Hepatotoxicity, Oxidative Stress, Fibrosis and Apoptosis in Rats

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      PLoS ONE
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          Abstract

          The current study was aimed to evaluate the preventive effects of Indigofera oblongifolia leaf extract (IOLE) on lead acetate (PbAc)-induced hepatotoxicity in adult male Wistar rats. PbAc was intraperitoneally injected at a dose of 20 mg/kg body weight for 5 days alone or in combination with the IOLE (100 mg/kg). Liver lead concentration and oxidative stress markers such as lipid peroxidation, hydrogen peroxide, nitric oxide, and glutathione content were investigated in addition to the enzymatic antioxidant activities. PbAc injection caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, hydrogen peroxide, and nitric oxide, with a concomitant decline in the glutathione content compared with the control, accompanied by a significant inhibition of antioxidant enzyme activities. The induction of oxidative stress, lead accumulation, and histological alterations in the liver were successfully minimized by pre-administration of IOLE. In addition, the PbAc group showed increase in the levels of Bax, caspase-3, and matrix metalloproteinase-9 proteins, while the expression of Bcl-2 protein was decreased. Prior administration of IOLE significantly mitigated apoptosis and fibrosis in the liver. Finally, the major components in I. oblongifolia extract were identified as polyphenols, flavonoids, and organic acids using liquid chromatography coupled mass spectroscopy. Thus, the findings of the current study revealed that I. oblongifolia had protective, anti-fibrotic, antioxidant, and anti-apoptotic activities on PbAc-induced hepatotoxicity. The beneficial effects of I. oblongifolia were in part mediated by Nrf2/HO-1 pathway.

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          Most cited references28

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          Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids.

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            Oxidative stress-related molecules and liver fibrosis.

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              Emerging role of Nrf2 in protecting against hepatic and gastrointestinal disease.

              Transcription factor NF-E2-related factor 2 (Nrf2) belongs to the basic region-leucine zipper family and is activated in response to electrophiles and reactive oxygen species. Nrf2 coordinately regulates the constitutive and inducible transcription of a wide array of genes involved in drug metabolism, detoxification, and antioxidant defenses. During periods of oxidative stress, Nrf2 is released from sequestration in the cytoplasm and translocates to the nucleus. Nrf2 binds antioxidant response elements (AREs) in the regulatory regions of target genes and activates transcription. Genetically modified mice lacking Nrf2 serve as a useful tool for identifying new ARE-regulated genes and assessing the ability of Nrf2 to confer protection against a variety of pathologies in numerous organs including the liver, intestine, lung, skin, and nervous system. With regards to the liver and gastrointestinal tract, Nrf2 knockout mice are more susceptible to acetaminophen-induced hepatocellular injury, benzo[a]pyrene-induced tumor formation and Fas- and TNFalpha -mediated hepatocellular apoptosis. The higher sensitivity of Nrf2 knockout mice to chemical toxicity is due in part to reduced basal and inducible expression of detoxification enzymes. Nrf2 may also be important in protecting against liver fibrosis, gallstone development, and formation of aberrant crypt foci. Research of Nrf2 has opened up new opportunities in understanding how antioxidant defense pathways are regulated, how oxidative stress contributes to disease progression and may serve as a novel target for designing therapies to prevent and treat diseases in which oxidative stress is implicated.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 July 2016
                2016
                : 11
                : 7
                : e0158965
                Affiliations
                [001]Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
                University of South Alabama Mitchell Cancer Institute, UNITED STATES
                Author notes

                Competing Interests: The author has declared that no competing interests exist.

                Conceived and designed the experiments: AEAM. Performed the experiments: AEAM. Analyzed the data: AEAM. Contributed reagents/materials/analysis tools: AEAM. Wrote the paper: AEAM.

                Article
                PONE-D-16-05462
                10.1371/journal.pone.0158965
                4938219
                27391413
                f55c8aaa-9eb3-4797-b2c2-350a52bfdfc2
                © 2016 Ahmed E. Abdel Moneim

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 3 March 2016
                : 26 June 2016
                Page count
                Figures: 10, Tables: 2, Pages: 18
                Funding
                The author received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Antioxidants
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Hepatocytes
                Biology and Life Sciences
                Anatomy
                Liver
                Hepatocytes
                Medicine and Health Sciences
                Anatomy
                Liver
                Hepatocytes
                Physical Sciences
                Chemistry
                Chemical Elements
                Lead (Element)
                Biology and Life Sciences
                Cell Biology
                Oxidative Stress
                Biology and Life Sciences
                Cell Biology
                Cell Processes
                Cell Death
                Apoptosis
                Biology and Life Sciences
                Biochemistry
                Lipids
                Lipid Peroxidation
                Biology and Life Sciences
                Biochemistry
                Peptides
                Glutathione
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Fatty Liver
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

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