Hepatic Malondialdehyde Levels Research Articles

Naringin prevents cyclophosphamide-induced hepatotoxicity in rats by attenuating oxidative stress, fibrosis, and inflammation

Cyclophosphamide (CYCP), a synthetic alkylating antineoplastic, disrupts both cancerous and non-cancerous cells to cause cancer regression and multi organotoxicity respectively. CYCP-induced hepatotoxicity is rare but possible. Evidence has shown that naringin has several beneficial potentials against oxidative stress, inflammation, and fibrosis. This study examined the chemoprotective potentials of naringin on exited radical scavenging, hepatic integrity, oxidative stress, fibrosis, and inflammation in CYCP-mediated hepatotoxicity. Rats were pre-treated orally by gavage for fourteen consecutive days with three doses (50, 100, and 200 mg/kg) of naringin before single CYCP (200 mg/kg, i.p.) administration. Subsequently, the rats were euthanized; blood and liver were removed, and assessed for serum and hepatic enzymes, oxidative stress, inflammation, and gene expression dynamics. Naringin concentrations required for 50% scavenging hydroxyl radical and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) radical cation were 0.32 mg/mL and 0.39 mg/mL, respectively. Pretreatment with naringin significantly (p < 0.05) abolish CYCP-induced changes in the activities of serum and hepatic ALT, AST, GGT, ALP, and LDH. Pretreatment with naringin remarkably (p < 0.05) reversed CYCP-mediated increases in hepatic levels of malondialdehyde, hydroperoxide, and nitric oxide; reverse CYCP-induced decreases in the hepatic glutathione levels, activities of catalase, glutathione peroxidase, and glutathione reductase; and also attenuated CYCP-induced upregulation of expression of hepatic chemokine (C-C motif) ligand 2 (CCL2), interferon alpha1 (IFN-α1), interleukine-1β, interleukine-1 receptor, and transforming growth factor beta 1 (TGF-β1). Taken together, different doses of naringin can prevent CYCP-induced oxidants generation, hepatocytes dysfunctions, oxidative stress as well as inflammatory perturbations in rats when pre-administered for as few as 14 days.

Bioactive Compounds from Mango peels (Mangifera indica .Tommy Atkins) And Demonstration of its Cytotoxicity and CCl4 Induced Hepatotoxicity in Rat

Mangifera indica (Tommy Atkins) peels, commonly known as mango, is a pharmacologically, ethnomedically, and phytochemically diverse plant. Peels is a major by-product during processing of mango fruit into pulp. In the present study, Thirteen pure bioactive compounds were isolated from methanolic peels extract. Six of them are new ellagitannins,namely,1,2,3,4,6 -Penta-O-galloyl-s-4C1-glupyranose (3); 2,3,6-Tri-O-galloyl-(α/β)-4C1-glucopyranose(4); 2,3-Di-O-galloyl-(α/β)-4C1-glucopyranose,Nilocitin(6);3,6-Di-O-galloyl-(α/β)-4C1-glucopyranose(8);1,6 -Di-O-galloyl- β-4C1-glucopyranose (9) ; 1,3-Di-O-galloyl-β-4C1- glucose (11), which were analyzed for the first time from M. indica (Tommy Atkins) peels. The ameliorative effect of the methanolic extract of M. indica (Tommy Atkins) peels towards the CCl4-induced hepatotoxicity in male Wistar rats through measuring certain biochemical parameters content in the liver were analyzed. The CCl4-treated rats showed a significant decline in the studied the serum levels of high-density lipoprotein (HDL), albumin (A) as well as the hepatic levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD) , glutathione reductase (GR), elevation in the levels of total lipids (TL), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), globulin (G), total bilirubin (TBil) , alanine and aspartate aminotransferase and alkaline phosphatase (ALAT and ASAT, ALP) and the hepatic levels of malondialdehyde (MDA). In contrast, the administration of methanol extract, notably improved all the studied parameters. This study showed that CCl4 administration to Wistar rats, at a high dose level, could induce a hepatic injury in addition to certain metabolic alterations. The work was extended to investigate tissue histopathology. Thus, results suggest that the peels extract can be a potential source of an attractive candidate for ameliorating of hepatotoxicity induced by CCl4 through scavenging free radicals, improved liver functions, and normalizing the liver histopathological architecture.

Hepatoprotective effect of Betulin against Cisplatin‐induced toxicity via inhibiting apoptotic and Nek7‐independent NLRP3 inflammasome pathways: An in vivo study

Background Despite its wide use, cisplatin induces serious multiorgan toxicity via stimulating vicious inflammatory, oxidative stress and apoptotic cascades. Betulin is a naturally occurring triterpene that has been shown to protect against cisplatin-induced nephrotoxicity, yet its protective effect against cisplatin-induced hepato- and cardiotoxicity has not been studied. Aim of the work Here we investigated the potential protective effect of betulin against cisplatin-induced hepatotoxicity in rats and the potential underlying mechanism of this effect. Methods Induction of cisplatin acute hepatotoxicity was achieved by single intraperitoneal injection of 10 mg/kg in the middle of the experimental model timeframe. Betulin treatment (8 mg/kg) was intraperitoneally injected daily for total period of 10 days. Results Treatment with betulin significantly improved biochemical liver functions as indicated by restoring cisplatin disrupted levels of serum Aspartate transaminase (AST), Alanine transaminase (ALT), albumin and total bilirubin. In addition, betulin significantly improved histopathological structural features of liver tissues and significantly reduced hepatic tissue fibrosis turnover. Betulin hepatoprotective effect was mediated via reducing cisplatin-provoked oxidative stress, inflammation and apoptosis. Specifically, betulin increased hepatic total antioxidant capacity and decreased hepatic malondialdehyde levels compared to cisplatin group. In addition, betulin significantly attenuated cisplatin-induced NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome pathway activation as evident by downregulating hepatic tissue levels of NLRP3, caspase-1 and interleukin-1β (IL-1β). Interestingly, despite of the cisplatin-induced upregulation of the hepatic NLRP3 interacting protein, mitotic kinase NIMA-related kinase 7 (Nek7), betulin did not induce any significant alteration of its levels in liver tissues. Betulin significantly reduced cisplatin-induced apoptosis induction as indicated by significant reduction of the apoptotic proteins P53 and Bax, significant reduction of caspases-8, -9 and -3 and upregulation of the anti-apoptotic protein Bcl2. Conclusion To the best of our knowledge, this is the first study to address the hepatoprotective effect of betulin against cisplatin-induced liver injury through modulation of inflammatory and apoptotic pathways.

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: promising activity without the risk of hepatic adverse effect

BackgroundComplementary remedies such as the Chinese herb ‘Sheng Ma’ (Black cohosh; Actaea racemosa ‘AR’) are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products.MethodsWe investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS).ResultsBeneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes.ConclusionThis study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk.

Antioxidant effects of gum arabic on gentamycin-induced hepatotoxicity in rats

Background Gum arabic (GA) is an exudate obtained from Acacia senegal and A. seyal, and it contains a large amount of nonviscous soluble fiber. Experimental studies revealed its strong antioxidant properties. Gentamycin-induced hepatotoxicity has been reported in experimental animals. Gentamycin induces hepatoxicity mainly by generating free radicals and enhancing oxidative stress. Aim This study aimed to investigate the involvement of oxidative stress and the alteration of the oxidant–antioxidant balance in gentamycin-induced hepatotoxicity. In addition, this study explored the possible protection that can be afforded by GA, given its antioxidant potential. Materials and methods Forty adult male Albino rats’ weighing was used in this study. The animals were randomly divided into four groups. Group I served as control, which received normal mouse diet. Group II orally received GA through a gastric feeding tube for 8 days. Group III received a daily intraperitoneal injection of gentamycin. Group IV received gentamycin intraperitoneally plus orally for 8 days. Results The results of this study revealed significant elevation of serum alanine transaminase, hepatic malondialdehyde level, glutathione peroxidase, and glutathione S-transferase activities and reduction of hepatic Reduced Glutathione (GSH) and glutathione reductase activities in gentamycin-treated animals. Administration of GA with gentamycin intake restored the altered parameters to their normal values, whereas hepatic glutathione peroxidase and glutathione S-transferase activities were enhanced further. Conclusion This study demonstrated the antioxidant effect of GA and its protective role against gentamycin-induced hepatocyte injury. More studies are warranted to further reveal the underlying mechanisms of the antioxidant properties of GA, especially at the structural and molecular levels.

Quercetin prevents cadmium chloride-induced hepatic steatosis and fibrosis by downregulating the transcription of miR-21.

This study investigated if cadmium chloride (CdCl2 )-induced hepatic steatosis and fibrosis and the protective effect of quercetin (QUR) are mediated modulating the activity of miR-21, a known hepatic lipogenic and fibrotic miRNA. Male rats (n=8/group) were divided as control, control + QUR (50 mg/kg; orally), CdCl2 (10 moml/L; drinking water), CdCl2 + miR-21 antagomir (inhibitor) (16 mg/kg/first 3 days), and CdCl2 + QUR (50 mg/kg). Treatments were conducted for 20 weeks, daily. All treatments showed no effect on fasting glucose and insulin levels. Administration of either miR-21 or QUR prevented CdCl2 -induced hepatic damage, as well as lipid droplets and collagen deposition. They also reduced serum levels of ALT and AST and decreased serum and hepatic levels of total cholesterol, triglycerides, and low-density lipoproteins in CdCl2 -treated rats. Concomitantly, they reduced hepatic levels of reactive oxygen species, malondialdehyde, interleukin-6, and tumor necrosis factor-α, suppressed the activation of NF-kb P65, and increased hepatic levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), and superoxide dismutase (SOD). These effects were associated with reduced expression of SREBP1, TGF-β1, Smad3, and collagen1 A and increased expression of PPARα, CPT1, and smad7. Interestingly, QUR significantly lowered levels of miR-21 and increased the protein levels and activity of Nrf2, as well as levels of GSH and SOD in the livers of both the control and CdCl2 -treated rats. Of note, levels of Nrf2 were negatively correlated with the transcription of miR-21. In conclusion: QUR prevents CdCl2 -induced hepatic steatosis and fibrosis mainly through attenuating its ability to upregulate miR-21, at least, by upregulation of Nrf2.

GC/MS-Based Metabolomics Profiling Approach and Determination of Ameliorative effect of Chiliadenus montanus extract towards CCl4 induced Hepatotoxicity in Albino Rats

The current study aimed to evaluate the GC/MS profiling of Chiliadenus montanus leaves extract which consists of 48 compounds, nine of them are major and represented 52.55 % from the total peak areas. The ameliorative effect towards the CCl4-induced hepatotoxicity in male Wistar rats through measuring certain biochemical parameters content in the liver were analyzed. CCl4 diluted 1:9 (v/v) in olive oil was injected intraperitoneally followed by oral administration of methanolic plant extract (200 mg/kg body weight). The CCl4-treated rats showed a significant decline in the studied hematological parameters, the serum levels of high-density lipoprotein (HDL), albumin (A) as well as the hepatic levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD) , glutathione reductase (GR), elevation in the levels of total lipids (TL), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), globulin (G), total bilirubin (TBil) , alanine and aspartate aminotransferase and alkaline phosphatase (ALAT and ASAT, ALP) and the hepatic levels of malondialdehyde (MDA). In contrast, the administration of methanol extract, notably improved all the studied parameters. This study showed that CCl4 administration to Wistar rats, at a high dose level, could induce a hepatic injury in addition to certain hematologic and metabolic alterations. The work was extended to examine tissue histopathology. In conclusion, C. montanus leaves methanol extract, resulted in an attractive candidate for ameliorating of hepatotoxicity induced by CCl4 through scavenging free radicals, improved liver functions, and normalizing the liver histopathological architecture. Yet, the treatment with methanol extract could ameliorate these alterations via their antioxidative effect. Further studies are required in order to identify the molecules responsible of the pharmacological activities.

The Impact of Antarctic Ice Microalgae Polysaccharides on D-Galactose-Induced Oxidative Damage in Mice

Antarctic ice microalgae (Chlamydomonas sp.) are a polysaccharide-rich natural marine resource. In this study, we evaluated the impact of Antarctic ice microalgae polysaccharides (AIMP) on D-galactose-induced oxidation in mice. We conducted biological and biochemical tests on tissue and serum samples from mice treated with AIMP. We found that AIMP administration was associated with improved thymus, brain, heart, liver, spleen, and kidney index values. We also found that AIMP treatment inhibited the reduced aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, superoxide dismutase, glutathione peroxidase, and glutathione levels as well as the increased serum, splenic, and hepatic nitric oxide and malondialdehyde levels arising from oxidation in these animals. Pathological examination revealed that AIMP also inhibited D-galactose-induced oxidative damage to the spleen, liver, and skin of these animals. AIMP was additionally found to promote the upregulation of neuronal nitric oxide synthase, endothelial nitric oxide synthase, cuprozinc-superoxide dismutase, manganese superoxide dismutase, catalase, heme oxygenase-1, nuclear factor erythroid 2-related factor 2, γ-glutamylcysteine synthetase, and NAD(P)H dehydrogenase [quinone] 1 as well as the downregulation of inducible nitric oxide synthase in these animals. High-performance liquid chromatography analysis revealed AIMP to be composed of five monosaccharides (mannitol, ribose, anhydrous glucose, xylose, and fucose). Together, these results suggest that AIMP can effectively inhibit oxidative damage more readily than vitamin C in mice with D-galactose-induced oxidative damage, which underscores the value of developing AIMP derivatives for food purposes.

Effects of high fructose diet on lipid metabolism and the hepatic NF-κB/ SIRT-1 pathway

ABSTRACT The liver is the primary site for fructose metabolism; therefore, the liver is susceptible to fructose related metabolic disturbances including metabolic insulin dysfunction, dyslipidemia and inflammation. We investigated whether astaxanthin (ASX) can modify hepatic nuclear factor-kappa B (NF-κB)/sirtuin-1 (SIRT-1) expression to alter oxidative stress caused by ingestion of excess fructose in rats. The animals were divided randomly into two x two factorially arranged groups: two regimens were given either water (W) or 30% fructose in drinking water (F). These two groups were divided further into two subgroups each: two treatments, either orally with 0.2 ml olive oil (OO) or 1 mg ASX/kg/day in 0.2 ml olive oil (ASX). Fructose administration increased serum glucose, triglycerides and very low density lipoproteins, and decreased serum concentration of high density lipoproteins; fructose did not alter serum total cholesterol. Excess fructose decreased hepatic superoxide dismutase (SOD) and increased hepatic NF-κB and MDA levels. ASX treatment increased hepatic SIRT-1 and decreased hepatic NF-κB and malondialdehyde (MDA) levels. ASX treatment decreased hepatic NF-κB and increased SOD levels, but did not alter MDA level in rats fed high fructose. ASX administration ameliorated oxidative stress caused by excess fructose by increasing hepatic NF-κB and SIRT-1 expression.

Effects of concurrent eight-week aerobic trainings and Rosa canina L. fruit hydroalcoholic extract on liver enzymes and malondialdehyde of liver in male rats following an acute aerobic exercise until exhaustion

Background: Rosa canina L. has high levels of carotenoids, flavonoids and, vitamin C antioxidant compounds that can withstand the destructive effects of exhaustive exercise-induced oxidative stress. The present study aims to investigate the effects of concurrent eight-week aerobic training and Rosa canina L. fruit hydroalcoholic extract on some liver enzymes and malondialdehyde of liver in male rats following an acute aerobic exercise until exhaustion. Methods: The present research was an experimental study. Forty male Wistar rats were randomly divided into four groups (N=10): placebo (without exercise + distilled water 2 ml supplement), supplement (without exercise + Rosa canina L extract, 100 mg/kg), exercise (8 weeks exercise + distilled water 2 ml), combined (8 weeks exercise + Rosa canina L extract, 100 mg/kg). At the end of the experiment, half of the rats were killed immediately before exhaustive exercise; while the other half were killed immediately after performing an acute exhaustive exercise on the treadmill. Serum enzymes AST, ALT, and hepatic malondialdehyde levels were measured by ELISA and thiobarbituric acid methods, respectively. Results: The results show that in all groups except the combined group serum AST, ALT, and malondialdehyde of the liver were significantly increased following an acute exhaustive exercise compared to the prior exhaustive exercise (P&lt;0.05). Conclusion: The use of Rosa canina L Fruit hydroalcoholic extract with aerobic exercise prevented the increase of hepatic malondialdehyde and serum enzymes AST, ALT levels following an acute exhausting exercise.

Contribution of polyol pathway, p16, and tristetraprolin to chemically induced liver injury

Background Hepatocellular carcinoma (HCC) is the most common cause of mortality and morbidity related to cancer in Egypt. Garlic with its organosulfur content has the ability to lower the risk of certain cancers. Aims The aim was to see the importance of polyol pathway, redox status, p16, and RNA-binding protein tristetraprolin (TTP) in chemically induced liver injury and subsequent cancer in addition to the role played by garlic extract in chemoprevention. Materials and methods In total, 50 male rats were allocated in four groups at random. Group II received garlic extract (0.4 g/100 g body weight) by oral gavage, HCC was induced chemically in groups III and IV by single intraperitoneal dose of diethylnitrosamine (200 mg/kg body weight) and maintained on a weekly subcutaneous injection of carbon tetrachloride (3 ml/kg body weight) for 10 weeks. Group IV received garlic extract in parallel with the induction. Hepatic p16 and TTP levels were immunoassayed. Moreover, hepatic function tests, aldose reductase activity, and redox status (malondialdehyde and catalase) were evaluated, in addition to the histological evaluation. Results Aspartate aminotransferase, alanine aminotransferase, hepatic malondialdehyde level, and aldose reductase activity were increased in the HCC group upon induction. Meanwhile, serum albumin, hepatic p16 and TTP level, and catalase activity were decreased. Garlic administration in parallel with the induction reverses the obtained biochemical changes and protected against chemical induction of HCC. Histological findings confirmed the laboratory results. Conclusion Garlic could protect against diethylnitrosamine/carbon tetrachloride −induced HCC and so it may be effective in protecting the liver against chemically induced hepatocyte damage and cancer.

Ameliorating and anti-inflammatory role of Balanites aegyptiaca aqueous extract on Doxorubicin-induced hepatotoxicity in male Wistar rats

Background and objective Doxorubicin (Doxo) is an antibiotic that used in cancer treatment, with many complications like hepatotoxicity. The objective of this study was to explore the ameliorative effect of Balanites aegyptiaca aqueous extract (BAE) against Doxo-induced hepatotoxicity in male rats. Materials and methods Adult male Wistar rats (140–160 g) were randomly divided into six groups (10 animals each) as follows: group I, normal rats act as a control group; group II, rats ingested with BAE (200 mg/kg) for 4 weeks; group III, rats intoxicated (intraperitoneal) with Doxo (0.5 mg/kg) for 4 weeks; group IV, rats ingested with BAE in combination with Doxo injection for 4 weeks; group V, rats ingested with BAE for 4 weeks before Doxo injection for another 4 weeks; and group VI, rats ingested with BAE for 4 weeks after Doxo injection. Results The results revealed all BAE regimens succeeded to decrease the hepatotoxicity induced by Doxo. This was evidenced by the significant reduction of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, urea, creatinine, tumor necrosis factor alpha, and interleukin-1beta levels, as well as hepatic malondialdehyde and nitric oxide levels. Moreover, a marked increase was observed in serum protein and albumin levels, as well as hepatic-reduced glutathione, superoxide dismutase, and catalase values. The obvious histopathological regenerations came in line with both serum and tissue biochemical findings. The Doxo-BAE combined regimen exhibited the highest potential of amelioration. Conclusion As a promising supplement, BAE exhibited hepatoprotective potential against Doxo-induced hepatic injuries; this could be mechanized through its antioxidant and radical scavenging exhibition of its bioactive constituents.

Modulatory effect of Polyalthia longifolia leaves against cadmium-induced oxidative stress and hepatotoxicity in rats.

Background Cadmium serves as a major pollutant in the environment and it has been documented for its widespread harmful effects. This study sought to investigate the prophylactic and the curative effects of aqueous and methanolic leaf extracts of Polyalthia longifolia against cadmium-induced hepatotoxicity in rats. Methods Animals in group I served as the normal control and administered distilled water only for 14 days, group II was administered cadmium (4 mg/kg/body weight) for 7 days, groups III and IV rats served as the prophylactic group and were pre-treated with P. longifolia aqueous and methanolic leaf extract for 7 days and then exposed to cadmium for another 7 days, serving as pre-treatment group, groups V, VI, VII, and VIII served as curative groups and were first exposed to cadmium for 7 days and then post-treated with 100 and 200 mg/kg body weight of aqueous extract and 100 and 200 mg/kg body weight of methanolic extract P. longifolia for another 7 days. Results Pre- and post-treatment with both extracts of P. longifolia revealed a significant hepatoprotective ability by decreasing the alanine transaminase, alkaline phosphatase, aspartate transaminase, acid phosphatase, gamma glutamyl transferase enzymatic activities were elevated due to cadmium intoxication. Pre- and post-treatment with aqueous and methanolic extract of P. longifolia extract significantly decreased hepatic malondialdehyde levels, together with an improvement in the antioxidant status of superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase, and reduced glutathione of rats exposed to cadmium. Histopathology examinations also confirm the above biochemical findings. Conclusion The findings from this work suggested that P. longifolia may be beneficial in ameliorating the cadmium-induced hepatotoxicity and oxidative stress in rats.

Chemoprevention of DMH-Induced Early Colon Carcinogenesis in Male BALB/c Mice by Administration of Lactobacillus Paracasei DTA81.

We evaluated the effects of the probiotic candidate Lactobacillus paracasei DTA81 (DTA81) on liver oxidative stress, colonic cytokine profile, and gut microbiota in mice with induced early colon carcinogenesis (CRC) by 1,2-dimethylhydrazine (DMH). Animals were divided into four different groups (n = 6) and received the following treatments via orogastric gavage for 8 weeks: Group skim milk (GSM): 300 mg/freeze-dried skim milk/day; Group L. paracasei DTA81 (DTA81): 3 × 109 colony-forming units (CFU)/day; Group Lactobacillus rhamnosus GG (LGG): 3 × 109 CFU/day; Group non-intervention (GNI): 0.1 mL/water/day. A single DMH dose (20 mg/kg body weight) was injected intraperitoneally (i.p), weekly, in all animals (seven applications in total). At the end of the experimental period, DTA81 intake reduced hepatic levels of carbonyl protein and malondialdehyde (MDA). Moreover, low levels of the pro-inflammatory cytokines Interleukin-6 (IL-6) and IL-17, as well as a reduced expression level of the proliferating cell nuclear antigen (PCNA) were observed in colonic homogenates. Lastly, animals who received DTA81 showed an intestinal enrichment of the genus Ruminiclostridium and increased concentrations of caecal acetic acid and total short-chain fatty acids. In conclusion, this study indicates that the administration of the probiotic candidate DTA81 can have beneficial effects on the initial stages of CRC development.

Suppression of inflammatory cascades via novel cinnamic acid nanoparticles in acute hepatitis rat model

Hepatitis was characterized by extreme inflammation and hepatocellular damage. Therefore, the current study aimed to gain insights into the modulation role of Cinnamic acid nanoparticles (CANPs) against acute hepatitis induced by d-Galactosamine and gamma radiation exposure (D-Gal/radiation) in the rat model and to suggest the implied molecular mechanism of CANPs. Acute hepatitis seriousness and the serum enzyme activities of ALT, AST, and ALP have been diminished upon oral administration of CANPs. Besides, the hepatic tissue levels of malondialdehyde (MDA) and nitric oxide (NO) have been significantly decreased, and the total antioxidant activity (TAO) depletion was extremely restored. Furthermore, the reduction of hepatic damage caused by pretreatment with CANPs was accompanied by significant suppression in the levels of hepatic proinflammatory cytokines (TNF-α, IL-1β, and IL-18), NF-κB, NLRP3, caspase-1 and proapoptotic protein BAX whereas anti-apoptotic protein Bcl-2 level significantly elevated as compared with D-Gal/radiation-induced acute hepatitis (AH) group. Also, CANPs suppress the D-Gal/radiation-induced IL-1β, IL-18, and ASK1 mRNA gene expression and the protein expression of TLR4 and MyD88 in the hepatic tissue. These biochemical parameters are confirmed by histological examination of the liver tissues. The present results indicated that CANPs can protect the hepatic cells from damage by both its anti-inflammatory and antioxidant influence as well as by modulating oxidation cellular pathways that have contributed to the acute severity of hepatitis. Also, CANPs is capable of suppressing apoptosis. Consequently, Nanoparticles of Cinnamic acid have the medicinal ability to protect the liver from acute hepatitis.

The Potential Hepatoprotective and Antioxidant Activities of Astragalus davisii against Paracetamol Induced Liver Damage in Rats

The current study aimed to estimate in vitro antioxidant effect of Astragalus davisii (A. davisii) extract. Further, the possible protective effect of A. davisii against paracetamol (PCM)-induced liver injury was assessed in rats. A. davisii was tested for its antioxidant activity using DPPH radical scavenging assay. The hepatoprotective potential of the extract was assessed in rats following oral administration for 7 days. Liver injury was induced in rats following oral administration of PCM overdose. Hepatic biomarkers; alanine-aminotransferase, aspartate-aminotransferase, alkaline-phosphatase, γ-glutamyl transferase and bilirubin were increased, while total protein and albumin were reduced in PCM control animals. Additionally, the activities of superoxide dismutase (SOD), catalase and glutathione-peroxidase (GPx) and the levels of glutathione were significantly declined, while levels of hepatic malondialdehyde (MDA) were significantly elevated in PCM alone treated rats. Oral administration of A. davisii (400 mg/kg) prior to PCM inhibited the elevation in the levels of liver damage markers in serum and protected against oxidative stress. Histopathological remarks confirmed the hepatoprotective potential of the extract. The results suggest that A. davisii extract at 400 mg/kg protects liver against injury induced by PCM overdose.

Regulating effect of Lactobacillus plantarum CQPC03 on lipid metabolism in high-fat diet-induced obesity in mice.

Probiotics are regard as safety approaches for preventing and treating some chronic diseases. This study investigated the regulating effect of Lactobacillus plantarum CQPC03 (LP-CQPC03) on lipid metabolism in high-fat diet (HFD)-induced obesity in mice. The results showed that administration of LP-CQPC03 at a concentration of 1.0×109 CFU/kg body weight inhibits HFD-induced obesity and improves lipid metabolism in the liver and serum. LP-CQPC03 intervention attenuated obesity-induced hepatic tissue damage, led decreases in hepatic triglyceride (42.02mmol/gprot), total cholesterol (3.85mmol/gprot), and LDL-C (1.03mmol/gprot), and an increase in HDL-C (1.07mmol/gprot). The same tendencies were observed in serum of HFD-fed mice. LP-CQPC03 intervention led a decrease in serum levels of aspartic transaminase, alanine transaminase, and alkaline phosphatase. LP-CQPC03 alleviated inflammation by increasing the level of interleukin (IL)-4 and IL-10, and decreasing the levels of pro-inflammatory factors, including IL-6, IL-1β, tumor necrosis factor-α, and interferon-γ. LP-CQPC03 also increased activities of SOD and GSH-Px in liver significantly and dropped the hepatic malondialdehyde (MDA) level from 3.39nmol/gprot to 1.90nmol/gprot. RT-qPCR results showed that the lipid metabolism-improving effect of LP-CQPC03 was performed by upregulating the expression of carnitine palmitoyltransferase 1, lipoprotein lipase, catalase, and superoxide dismutase 1. This study indicates that L. plantarum CQPC03 might be a potential probiotic that can help mitigate the adverse effects of excessive lipids on the liver, and prevent or alleviate high-energy intake-related obesity. PRACTICAL APPLICATIONS: Intaking high-energy foods is a potential risk of lipid metabolic disorder. Therefore, it is necessary to seek an effective and safe approach for preventing the obesity-related disease. This study found that LP-CQPC03 limited the rate of increase in body weight of mice fed on HFD, maintained normal hepatic tissue morphology, and exhibited a strong regulating effect on lipid metabolism. And the threshold concentration of LP-CQPC03 for the lipid-lowering effect was 1.0×109 CFU/kg body weight. Therefore, LP-CQPC03 is a potential probiotic for preventing or alleviating high-energy intake-related obesity.

Oregano (Origanum vulgare), St John's-wort (Hypericum perforatum), and lemon balm (Melissa officinalis) extracts improved the growth rate, antioxidative, and immunological responses in Nile tilapia (Oreochromis niloticus) infected with Aeromonas hydrophila

The present study was designed to evaluate the effects of ethanolic extracts of Hypericum perforatum (HP), Origanum vulgare (ORG), and Melissa officinalis (MOF) on Nile tilapia (Oreochromis niloticus) juveniles. Fish (16.92 ± 0.28 g) were randomly divided into seven groups fed on diets with 0 % (CTR), and two levels (0.2 % and 0.5 %) from each plant extract for 60 days. Final body weight, weight gain %, specific growth rate, and feed conversion ratio were significantly improved in the groups fed with ORG and MOF at 0.5 % (P < 0.05). Moreover, ORG 0.5 % and MOF 0.5 % groups showed a significant increase in RBCs and WBCs counts as well as the hematocrit and hemoglobin values (P < 0.05). Besides, significant enhancement was noticed in the levels of intestinal digestive enzymes in the MOF 0.5 % group (P < 0.05). Activities of hepatic superoxide dismutase, glutathione peroxidase, catalase were significantly improved, meanwhile, the hepatic malondialdehyde levels were significantly decreased in all groups fed on phytogenic diets compared to the CTR group (P < 0.05). Furthermore, ORG 0.5 % and MOF 0.5 % groups showed a significant increase in serum total protein, and alternative complement activity (ACH50) (P < 0.05). Attractively, serum lysozyme levels were significantly increased while serum endotoxin values decreased in all groups fed on phytogenic diets. Furthermore, the MOF 0.5 % group showed the highest activities of skin mucus lysozyme, ACH50, and protease (P < 0.05), meanwhile mucosal total immunoglobulins were the highest in ORG 0.5 % and both levels of MOF. ORG 0.5 % and MOF 0.5 % groups showed the highest protection levels of fish following challenge with pathogenic Aeromonas hydrophila. Conclusively, this comparative study showed that both ORG and MOF extract at a 0.5 % level can effectively improve the growth, health, and immune status of Nile tilapia juveniles.

Ameliorative effects of hexane extract of Garcinia kola seeds Heckel (Clusiaceae) in cisplatin-induced hepatorenal toxicity in mice

Garcinia kola seed is used to manage liver diseases in ethnomedicine. However, there is limited information on its role in Cisplatin (CIS)-induced toxicity. Here, we investigated the potential of hexane extract of Garcinia kola (HEGK) in lessening CIS-induced hepatorenal- and gene- toxicity. Male mice (22 ± 3 g) randomly assigned into groups (n = 5) were treated for five days: Corn oil only, HEGK (200 mg/kg), CIS (20 mg/kg; i.p; 48-hours), CIS + HEGK (100 mg/kg), CIS + HEGK (200 mg/kg), CIS + Quercetin (25 mg/kg), and Quercetin(25 mg/kg). Corn oil, HEGK, and Quercetin were administered daily by gavage. GC-MS revealed the presence of 9,19-Cyclolanost-24-en-3-ol as the most abundant component in HEGK, with an LC50 of 1023 µg/mL. HEGK significantly (p < 0.05) scavenged DPPH, inhibited lipid peroxidation and exhibited reducing activity dose-dependently. CIS treatment increased (p < 0.05) urinary albumin and creatinine by 18 and 56%, respectively, serum levels of total bilirubin, creatinine, and hepatic transaminases, while albumin decreased (p < 0.05) by 57%. CIS treatment increased renal and hepatic malondialdehyde (MDA) levels by 67 and 70% individually, while the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels were decreased (p < 0.05). Furthermore CIS-induced the formation of mononucleated polychromatic erythrocytes (mnPCEs) 150% in the bone marrow of mice. Histology revealed necrosis of hepatocytes, congestion of renal interstitial vessel, and hyperplasia of the Kupffer cells. Pretreatment with HEGK reduced the levels of MDA, mnPCEs, and increased the activities of antioxidant enzymes and restored GSH to levels comparable in control mice. Taken together, HEGK ameliorated CIS-toxicity via the activation of the antioxidative pathways and mitigated genotoxicity by mitigating mnPCEs formation in mice.

Effects of dietary thyme (Zataria multiflora) extract on antioxidant and immunological responses and immune-related gene expression of rainbow trout (Oncorhynchus mykiss) juveniles

Effects of dietary hydroalcoholic extract of Zataria multiflora (ZE) on growth performance, plasma and hepatic antioxidant capacities, and humoral and skin mucus immune parameters were evaluated in rainbow trout (Oncorhynchus mykiss) juveniles. in vitro tests showed that ZE had antioxidant property comparable to butylated hydroxytoluene (BHT) at 100–200 μg/mL concentrations, although its antioxidant property was lower than BHT at concentration below 100 μg/mL. Moreover, ZE had anti-bacterial activity against Aeromonas hydrophila, which was 30–50% lower than that of tetracycline. After feeding the fish with diets supplemented with 0 (CT, 1 (ZE1), 2 (ZE2), and 3 (ZE3) g/kg ZE for eight weeks, there were no significant differences in growth performance and feed efficiency among the treatments; however, the fish in ZE2 and ZE3 treatments showed significantly higher survival than the fish in CT treatment. Blood leukocyte counts, plasma globulin, total immunoglobulin, lysozyme and bactericidal activity against A. hydrophila in ZE2 and ZE3 groups were significantly higher than that of CT group. All the ZE-treated groups had higher plasma complement activity compared to the CT group. Mucosal lysozyme and bactericidal activities of the ZE2 fish were significantly higher than the other treatments. Expression of tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, and lysozyme genes increased in head kidney of the fish treated with ZE; the highest increases were related to the ZE2 treatment. Plasma total antioxidant (TA) activities of ZE2 and ZE3 treatments were significantly higher than that of the CT treatment. Plasma and hepatic superoxide dismutase (SOD) and catalase (CAT) activities of ZE2 group were significantly higher than the other treatments. Plasma malondialdehyde (MDA) levels were significantly lower in ZE2 treatment, compared to the other treatments. However, hepatic MDA level of ZE2 treatment was significantly lower than those of the ZE1 and CT treatments. In conclusion, dietary ZE supplementation level of 2 g/kg is suggested for rainbow trout feed supplementation to augment fish survival, antioxidant and immune strength.