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      Evaluation of hematoprotective, hepatoprotective, and anti-inflammatory potentials of chia seed ( Salvia hispanica L.) extract in rats

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          Abstract

          This study was conducted to evaluate the effects of chia seed extract on CCl 4-induced hepatotoxicity, hematological profile, and carrageenan-induced inflammation in rats. Water-ethanol-acetone extract of chia seeds at the doses of 200 and 400 mg/kg body weight/day were applied to evaluate the comparative protective roles. Hematological profile and serum biochemical parameters were measured to evaluate the hematoprotective, and hepatoprotective effects of chia seed extract. Paw thickness and motility level were assessed at 0, 1, 3, 5, and 7 h after sub-planter injection of carrageenan to evaluate the anti-inflammatory potential. Tissue histopathology was performed in both cases. Chia seed extract reduced the elevated level of serum AST and ALT significantly in a dose-dependent manner following intra-peritoneal injection of CCl 4. Histopathological study of the liver tissue exhibited acute impairment of the hepatocytes and liver parenchyma following CCl 4 exposure, which was markedly regenerated by the chia seed extract treatment. Protective effects of the extracts were also evidenced by the RBC count, Hb (%), PCV (%), ESR, and neutrophil count. Chia seed extract was found to inhibit the carrageenan-induced paw edema and increase motility level in a dose-oriented fashion. Histological examination of the paw tissue revealed severe inflammation characterized by massive infiltration of inflammatory cells in the carrageenan group, which was significantly reduced by chia seed extract treatment. The higher dose of chia seed extract showed significant increases in bodyweight gain and feed efficiency ratio but decrease in visceral fat deposition. These results suggest that chia seeds possess potentials for hematoprotective, hepatoprotective, and anti-inflammatory activities.

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          Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model.

          The use of many halogenated alkanes such as carbon tetrachloride (CCl4), chloroform (CHCl3) or iodoform (CHI3), has been banned or severely restricted because of their distinct toxicity. Yet CCl4 continues to provide an important service today as a model substance to elucidate the mechanisms of action of hepatotoxic effects such as fatty degeneration, fibrosis, hepatocellular death, and carcinogenicity. In a matter of dose,exposure time, presence of potentiating agents, or age of the affected organism, regeneration can take place and lead to full recovery from liver damage. CCl4 is activated by cytochrome (CYP)2E1, CYP2B1 or CYP2B2, and possibly CYP3A, to form the trichloromethyl radical, CCl3*. This radical can bind to cellular molecules (nucleic acid, protein, lipid), impairing crucial cellular processes such as lipid metabolism, with the potential outcome of fatty degeneration (steatosis). Adduct formation between CCl3* and DNA is thought to function as initiator of hepatic cancer. This radical can also react with oxygen to form the trichloromethylperoxy radical CCl3OO*, a highly reactive species. CCl3OO* initiates the chain reaction of lipid peroxidation, which attacks and destroys polyunsaturated fatty acids, in particular those associated with phospholipids. This affects the permeabilities of mitochondrial, endoplasmic reticulum, and plasma membranes, resulting in the loss of cellular calcium sequestration and homeostasis, which can contribute heavily to subsequent cell damage. Among the degradation products of fatty acids are reactive aldehydes, especially 4-hydroxynonenal, which bind easily to functional groups of proteins and inhibit important enzyme activities. CCl4 intoxication also leads to hypomethylation of cellular components; in the case of RNA the outcome is thought to be inhibition of protein synthesis, in the case of phospholipids it plays a role in the inhibition of lipoprotein secretion. None of these processes per se is considered the ultimate cause of CCl4-induced cell death; it is by cooperation that they achieve a fatal outcome, provided the toxicant acts in a high single dose, or over longer periods of time at low doses. At the molecular level CCl4 activates tumor necrosis factor (TNF)alpha, nitric oxide (NO), and transforming growth factors (TGF)-alpha and -beta in the cell, processes that appear to direct the cell primarily toward (self-)destruction or fibrosis. TNFalpha pushes toward apoptosis, whereas the TGFs appear to direct toward fibrosis. Interleukin (IL)-6, although induced by TNFalpha, has a clearly antiapoptotic effect, and IL-10 also counteracts TNFalpha action. Thus, both interleukins have the potential to initiate recovery of the CCl4-damaged hepatocyte. Several of the above-mentioned toxication processes can be specifically interrupted with the use of antioxidants and mitogens, respectively, by restoring cellular methylation, or by preserving calcium sequestration. Chemicals that induce cytochromes that metabolize CCl4, or delay tissue regeneration when co-administered with CCl4 will potentiate its toxicity thoroughly, while appropriate CYP450 inhibitors will alleviate much of the toxicity. Oxygen partial pressure can also direct the course of CCl4 hepatotoxicity. Pressures between 5 and 35 mmHg favor lipid peroxidation, whereas absence of oxygen, as well as a partial pressure above 100 mmHg, both prevent lipid peroxidation entirely. Consequently, the location of CCl4-induced damage mirrors the oxygen gradient across the liver lobule. Mixed halogenated methanes and ethanes, found as so-called disinfection byproducts at low concentration in drinking water, elicit symptoms of toxicity very similar to carbon tetrachloride, including carcinogenicity.
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            Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease

            Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide and is strongly associated with the presence of oxidative stress. Disturbances in lipid metabolism lead to hepatic lipid accumulation, which affects different reactive oxygen species (ROS) generators, including mitochondria, endoplasmic reticulum, and NADPH oxidase. Mitochondrial function adapts to NAFLD mainly through the downregulation of the electron transport chain (ETC) and the preserved or enhanced capacity of mitochondrial fatty acid oxidation, which stimulates ROS overproduction within different ETC components upstream of cytochrome c oxidase. However, non-ETC sources of ROS, in particular, fatty acid β-oxidation, appear to produce more ROS in hepatic metabolic diseases. Endoplasmic reticulum stress and NADPH oxidase alterations are also associated with NAFLD, but the degree of their contribution to oxidative stress in NAFLD remains unclear. Increased ROS generation induces changes in insulin sensitivity and in the expression and activity of key enzymes involved in lipid metabolism. Moreover, the interaction between redox signaling and innate immune signaling forms a complex network that regulates inflammatory responses. Based on the mechanistic view described above, this review summarizes the mechanisms that may account for the excessive production of ROS, the potential mechanistic roles of ROS that drive NAFLD progression, and therapeutic interventions that are related to oxidative stress.
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              Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective

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                Author and article information

                Contributors
                Journal
                Vet Anim Sci
                Vet Anim Sci
                Veterinary and Animal Science
                Elsevier
                2451-943X
                28 March 2024
                June 2024
                28 March 2024
                : 24
                : 100349
                Affiliations
                [a ]Department of Pharmacology, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh
                [b ]Department of Fisheries Technology, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh
                Author notes
                [* ]Corresponding author. drzahorul@ 123456bau.edu.bd
                Article
                S2451-943X(24)00016-4 100349
                10.1016/j.vas.2024.100349
                10999476
                38590834
                85a016d9-d2ba-41f2-985c-2a4ae1b8bb1a
                © 2024 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                chia seed,carbon tetrachloride,carrageenan,hepatoprotective,anti-inflammatory

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