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      Curcumin, an Active Constituent of Turmeric Spice: Implication in the Prevention of Lung Injury Induced by Benzo(a) Pyrene (BaP) in Rats

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          Abstract

          Benzo(a)pyrene (BaP) is a well-known carcinogen and enhances oxidative stress and apoptosis and also alters several molecular pathways. Curcumin is an active ingredient of Curcuma longa, and it has potent anti-inflammatory, antioxidant activity that defends cells from oxidative stress and cell death. The objectives of the present study were to explore the protective effects of curcumin against long-term administration of BaP induced disturbances in lungs of rats. Male rats were randomly divided into four groups: saline control, BaP only, BaP + curcumin, and curcumin only. Lung histopathology, electron microscopy, inflammatory cytokine release, antioxidant levels, apoptosis, and cell cycle were examined. Instillation of BaP significantly increased infiltration of inflammatory cells in alveolar space and inflammatory cytokine in blood. BaP induced lung tissue alterations including mild bronchitis, scant chronic inflammatory cell infiltrate in the wall of the respiratory bronchiole, and mild intra-alveolar haemorrhage. However, these alterations were found to be significantly less as mild inflammatory cell infiltrate in curcumin plus BaP treated group. Furthermore, electron microscopy results also showed necrotic changes and broken cell membrane of Type-II epithelial cell of alveoli in BaP group, which was reduced after adding curcumin treatment. In addition, we found BaP plus curcumin treatment effectively reduced inflammatory cytokines Tumour Necrosis Factor alpha (TNF-α), Interleukin 6 (IL-6), and C-reactive protein (CRP) levels in blood serum. Moreover, the levels of tunnel staining and p53 expression were significantly increased by BaP, whereas these changes were noticeably modulated after curcumin treatment. BaP also interferes in normal cell cycle, which was significantly improved with curcumin treatment. Overall, our findings suggest that curcumin attenuates BaP -induced lung injury, probably through inhibiting inflammation, oxidative stress and apoptosis in lung epithelial cells, and improving cell proliferation and antioxidants level. Thus, curcumin may be an alternative therapy for improving the outcomes of Benzo(a)pyrene-induced lung injury.

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          Regulation of superoxide dismutase genes: implications in disease.

          Numerous short-lived and highly reactive oxygen species (ROS) such as superoxide (O2(.-)), hydroxyl radical, and hydrogen peroxide are continuously generated in vivo. Depending upon concentration, location, and intracellular conditions, ROS can cause toxicity or act as signaling molecules. The cellular levels of ROS are controlled by antioxidant enzymes and small-molecule antioxidants. As major antioxidant enzymes, superoxide dismutases (SODs), including copper-zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase, and extracellular superoxide dismutase, play a crucial role in scavenging O2(.-). This review focuses on the regulation of the sod genes coding for these enzymes, with an emphasis on the human genes. Current knowledge about sod structure and regulation is summarized and depicted as diagrams. Studies to date on genes coding for Cu/ZnSOD (sod1) are mostly focused on alterations in the coding region and their associations with amyotrophic lateral sclerosis. Evaluation of nucleotide sequences reveals that regulatory elements of the sod2 gene reside in both the noncoding and the coding region. Changes associated with sod2 lead to alterations in expression levels as well as protein function. We also discuss the structural basis for the changes in SOD expression associated with pathological conditions and where more work is needed to establish the relationship between SODs and diseases.
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            Potential anticancer properties and mechanisms of action of curcumin.

            Curcumin, a yellow substance belonging to the polyphenols superfamily, is the active component of turmeric, a common Indian spice, which is derived from the dried rhizome of the Curcuma longa plant. Numerous studies have demonstrated that curcumin possesses anti-oxidant, anti-inflammatory and anticancerous properties. The purpose of this review is to focus on the anti-tumor effects of curcumin. Curcumin inhibits the STAT3 and NF-κB signaling pathways, which play key-roles in cancer development and progression. Also, inhibition of Sp-1 and its housekeeping gene expressions may serve as an important hypothesis to prevent cancer formation, migration, and invasion. Recent data have suggested that curcumin may act by suppressing the Sp-1 activation and its downstream genes, including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in a concentration-dependent manner in colorectal cancer cell lines; these results are consistent with other studies, which have reported that curcumin could suppress the Sp-1 activity in bladder cancer and could decrease DNA binding activity of Sp-1 in non-small cell lung carcinoma cells. Recent data advocate that ER stress and autophagy may as well play a role in the apoptosis process, which is induced by the curcumin analogue B19 in an epithelial ovarian tumor cell line and that autophagy inhibition could increase curcumin analogue-induced apoptosis by inducing severe ER stress. The ability of curcumin to induce apoptosis in tumor cells and its anti-angiogenic potential will be discussed in this review.
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              Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury.

              Catalase plays a major role in cellular antioxidant defense by decomposing hydrogen peroxide, thereby preventing the generation of hydroxyl radical by the Fenton reaction. The degree of catalase deficiency in acatalasemic and hypocatalasemic mice varies from tissue to tissue. They therefore may not be suitable for studying the function of this enzyme in certain models of oxidant-mediated tissue injury. We sought to generate a new line of catalase null mice by the gene targeting technique. The mouse catalase (Cat or Cas1) gene was disrupted by replacing parts of intron 4 and exon 5 with a neomycin resistance cassette. Homozygous Cat knockout mice, which are completely deficient in catalase expression, develop normally and show no gross abnormalities. Slices of liver and lung and lenses from the knockout mice exhibited a retarded rate in decomposing extracellular hydrogen peroxide compared with those of wild-type mice. However, mice deficient in catalase were not more vulnerable to hyperoxia-induced lung injury; nor did their lenses show any increased susceptibility to oxidative stress generated by photochemical reaction, suggesting that the antioxidant function of catalase in these two models of oxidant injury is negligible. Further studies showed that cortical injury from physical impact caused a significant decrease in NAD-linked electron transfer activities and energy coupling capacities in brain mitochondria of Cat knockout mice but not wild-type mice. The observed decrease in efficiency of mitochondrial respiration may be a direct result of an increase in mitochondrion-associated calcium, which is secondary to the increased oxidative stress. These studies suggest that the role of catalase in antioxidant defense is dependent on the type of tissue and the model of oxidant-mediated tissue injury.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                07 February 2020
                February 2020
                : 25
                : 3
                : 724
                Affiliations
                [1 ]Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah 52571, Saudi Arabia; smtrody@ 123456qu.edu.sa (S.A.A.); f_alrumaihi@ 123456qu.edu.sa (F.A.); shly@ 123456qu.edu.sa (M.A.A.); m.alhommrani@ 123456qu.edu.sa (M.F.A.)
                [2 ]Department of Basic Health Sciences, College of Applied Medical Science, Qassim University, Buraidah 52571, Saudi Arabia; 4140@ 123456qu.edu.sa
                Author notes
                [* ]Correspondence: ah.rahmani@ 123456qu.edu.sa ; Tel.: +3800050 (ext. 4835)
                Article
                molecules-25-00724
                10.3390/molecules25030724
                7037262
                32046055
                391fad2e-b7cb-49c7-8a56-bea5ac37faf9
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 January 2020
                : 05 February 2020
                Categories
                Article

                benzo(a)pyrene,lung injury,inflammation,antioxidant,apoptosis

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