Hepatic Lipid Peroxidation Levels Research Articles

Can Alpha-Pinene Prevent Methotrexate-Induced Cardiac and Hepatic Damage?

The effects of alpha-pinene (AP), a monoterpenoid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, on methotrexate (MTX)-induced cardiac and hepatic damage were investigated in this study. Male Sprague-Dawley rats were divided into Control, Vehicle, AP, MTX, and AP+MTX groups (n=7). AP (50 mg/kg/day, 14 days) was applied subcutaneously in the AP and AP+MTX groups. MTX (20 mg/kg) was injected three days before sacrification. Serum CK-MB, troponin T, ALT, and AST levels, as well as cardiac and hepatic MDA, GSH, caspase-3, and p53 levels, were measured by ELISA. Histological changes in tissues were evaluated by scoring in terms of tissue damage and cellular degeneration parameters after hematoxylin-eosin staining. MTX caused significant increase in serum CK-MB, troponin T, ALT, and AST levels, hepatic and cardiac lipid peroxidation, GSH depletion, and caspase-3 level. However, tissue levels of p53 did not change significantly. MTX-induced histological deterioration was observed in both tissues. These MTX-induced changes were significantly reduced in the AP+MTX group. Present results show that MTX-induced cardiac and hepatic damage is prevented by AP pretreatment. This protection can be attributed to the antioxidant and anti-apoptotic properties of AP. Considering the importance of MTX in cancer treatment, AP appears to have highly promising potential as a cardioprotective and hepatoprotective agent in anti-tumoral therapy.

Protective Effects of Xanthine Derivatives Against Arsenic Trioxide-Induced Oxidative Stress in Mouse Hepatic and Renal Tissues.

In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.

SAT665 Effects Of Weight Cycling On Hepatic Protein Carbonylation And Lipid Peroxidation

Abstract Disclosure: M.A. Djalali-Gomez: None. J.A. Bogart: None. S. Duran Ortiz: None. D.E. Berryman: None. J.J. Kopchick: None. E.O. List: None. Over two-thirds of the U.S. population is overweight or obese which has been shown to increase oxidative stress. Oxidative stress damages biological molecules such as lipids, proteins, and DNA, ultimately contributing to the development of numerous diseases including cancer and diabetes. Increasing awareness of the health issues caused by obesity leads many to attempt weight loss. Unfortunately, successful weight loss is usually temporary as an estimated 80% of individuals who lose weight will gain it back within a year. Repeated cycles of weight gain and weight loss are known as weight cycling. While the prevalence of obesity and weight cycling has increased in recent years, research on the long-term health consequences of weight cycling is limited. In the current study, we evaluated how diet stability (i.e., weight-cycled diets vs stable diets) and immediate diet (i.e., diet at the time of tissue collection; high fat vs low fat) affect oxidative stress by measuring hepatic lipid peroxidation and protein carbonylation from mice exposed to long term weight cycling or a stable diet regimen with high or low-fat diets. Our results indicate that the immediate diet significantly impacted hepatic oxidative stress, as mice on a high-fat diet prior to sacrifice had significantly greater levels of hepatic protein carbonylation (p=.020) as well as hepatic lipid peroxidation (p=.010) compared to mice on a low-fat diet. Importantly, our results also indicate that diet stability significantly impacted hepatic oxidative stress as weight cycled mice had significantly greater levels of hepatic protein carbonylation (p=.030) and hepatic lipid peroxidation (p=.008) compared to mice fed stable diets. Overall, our results indicate that weight cycling, independent of immediate diet, increases oxidative damage in the livers of mice compared with mice fed stable (non-cycled) diet regimens. Presentation: Saturday, June 17, 2023

Preventing acute liver injury via hepatocyte-targeting nano-antioxidants.

Acute liver injury (ALI) is a severe liver disease that is characterized by sudden and massive hepatocyte necrosis and deterioration of liver functions. Oxidative stress is increasingly recognized as a key factor in the induction and progression of ALI. Scavenging excessive reactive oxygen species (ROS) with antioxidants has become a promising therapeutic option, but intrinsically hepatocyte-targeting antioxidants with excellent bioavailability and biocompatibility are yet to be developed. Herein, self-assembling nanoparticles (NPs) composed of amphiphilic polymers are introduced to encapsulate organic Selenium compound L-Se-methylselenocysteine (SeMC) and form SeMC NPs, which protect the viabilities and functions of cultured hepatocytes in drug- or chemical-induced acute hepatotoxicity models via efficient ROS removal. After further functionalization with the hepatocyte-targeting ligand glycyrrhetinic acid (GA), the resultant GA-SeMC NPs exhibit enhanced hepatocyte uptake and liver accumulation. In mouse models of ALI induced by acetaminophen (APAP) or carbon tetrachloride (CCl4 ), treatment with GA-SeMC NPs significantly decrease the levels of hepatic lipid peroxidation, tissue vacuolization and serum liver transaminases, while prominently increase that of endogenous antioxidant enzymes. Our study therefore presents a liver-targeting drug delivery strategy for the prevention and treatment of hepatic diseases.

Evaluation of antiobesity and hepatorenal protective activities of Salvia officinalis extracts pre-treatment in high-fat diet-induced obese rats.

The present study evaluated the effects of Hail Salvia officinalis total extract (SOTE) and its high flavonoid fraction (SOHFF) on the high-fat diet (HFD)-induced obesity and hepatorenal damage in rats. Salvia officinalisplants were collected from Hail region, Saudi Arabia. Rats were fed HFD and supplemented orally with SOTE (250mgkg-1) or SOHFF (100mgkg-1) or simvastatin (SVS; 10mgkg-1) every day for 8weeks. Compared to the controls, HFD-induced obesity led to significant increases in body weight, body weight gained, blood insulin, leptin, cardiac enzymes (LDH and CPK) activity, and atherogenic index (AI). HFD rats also showed higher levels of hepatic and renal function biomarkers (ALT, urea, and creatinine), as well as lower levels of PPARγ and Nrf2-gene expression and a disrupted lipid profile. Moreover, HFD rats had lower levels of hepatic and renal antioxidant biomarkers (CAT, GPx, SOD, GR, and GSH), accompanied by higher levels of hepatic and renal lipid peroxidation (LPO), nitric oxide (NO), and inflammatory mediators (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)). In addition, histological examination of hepatic and renal tissues revealed histopathological changes that validated the biochemical findings. Compared to HFD group, SOTE and SOHFF treatment led to marked amelioration of all the aforementioned parameters. Collectively, supplementation with SOTE and SOHFF effectively reversed HFD-induced alterations through its antioxidant, hypolipidemic, and anti-inflammatory properties. Hence, SOTE and SOHFF have therapeutic potential in controlling obesity and related pathologies.

Probiotics Alleviate Oxidative Stress in H2O2-Exposed Hepatocytes and t-BHP-Induced C57BL/6 Mice

Antioxidants protect against oxidative stress that can damage proteins, the cellular immune system, and DNA. In recent studies, probiotics have been shown to impart a microbial balance to the gastrointestinal tract, demonstrating significant antioxidant capacity. In this study, the probiotic properties and antioxidant mechanism of probiotics were evaluated in HepG2 cells and in an animal model. The characteristics of Lactococcus lactis MG5125, Bifidobacterium bifidum MG731, and Bifidobacterium animalis subsp. lactis MG741, which were used as lactic acid bacteria in this study, were analyzed. The results revealed the safety and stability of these probiotics in the gastrointestinal tract because they did not cause hemolysis and had excellent intestinal adhesion (75–84%). In HepG2 cells, the three probiotics alleviated H2O2-induced oxidative stress by mediating lipid peroxidation and glutathione levels and upregulating antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. In the tBHP-induced mouse model, administration of the three probiotics reduced hepatic aspartate transaminase, alanine transaminase, and lipid peroxidation levels. In conclusion, Lc. lactis MG5125, B. bifidum MG731, and B. lactis MG741 showed considerable antioxidant activity both in vitro and in vivo.

Aging Induces Hepatic Oxidative Stress and Nuclear Proteomic Remodeling in Liver from Wistar Rats.

Aging is a continuous, universal, and irreversible process that determines progressive loss of adaptability. The liver is a critical organ that supports digestion, metabolism, immunity, detoxification, vitamin storage, and hormone signaling. Nevertheless, the relationship between aging and the development of liver diseases remains elusive. In fact, although prolonged fasting in adult rodents and humans delays the onset of the disease and increases longevity, whether prolonged fasting could exert adverse effects in old organisms remains incompletely understood. In this work, we aimed to characterize the oxidative stress and nuclear proteome in the liver of 3-month- and 24-month-old male Wistar rats upon 36 h of fasting and its adaptation in response to 30 min of refeeding. To this end, we analyzed the hepatic lipid peroxidation levels (TBARS) and the expression levels of genes associated with fat metabolism and oxidative stress during aging. In addition, to gain a better insight into the molecular and cellular processes that characterize the liver of old rats, the hepatic nuclear proteome was also evaluated by isobaric tag quantitation (iTRAQ) mass spectrometry-based proteomics. In old rats, aging combined with prolonged fasting had great impact on lipid peroxidation in the liver that was associated with a marked downregulation of antioxidant genes (Sod2, Fmo3, and Cyp2C11) compared to young rats. Besides, our proteomic study revealed that RNA splicing is the hepatic nuclear biological process markedly affected by aging and this modification persists upon refeeding. Our results suggest that aged-induced changes in the nuclear proteome could affect processes associated with the adaptative response to refeeding after prolonged fasting, such as those involved in the defense against oxidative stress.

Effect of Nigella sativa enriched diet on biochemical variables and antioxidant damage caused by silver nanoparticles toxicity in the African catfish, Clarias gariepinus

The present study aimed to investigate the effect of silver nanoparticles (AgNPs) (50 mg/L) on the behavioral changes, biochemical alterations, oxidative stress, and the histopathological changes in liver tissues of African catfish, clarias gariepinus. In addition to the potential role of Nigella sativa (NS) in ameliorating these effects. Fish were divided into four groups: group 1 was control fed on the basal diet, group 2 was fed on 3% (NS) of basal diet, group 3 was exposed to 50 mg/L AgNPs, and group 4 was exposed to 50 mg/L AgNPs and fed on 3% (NS) for 30 days. Results revealed that catfish in the group (3) exposed to AgNPs exhibited changes in skin pigmentation and abnormal behavior in the swim. A significant elevation (P<0.05) in levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) of catfish exposed to AgNPs compared to the control fish. Furthermore, a marked increase in hepatic lipid peroxidation (LPO), catalase (CAT), total antioxidant (TAC), glutathione (GSH), and superoxide dismutase (SOD) levels were recorded in the group (3). Alternatively, feeding exposed catfish to AgNPs on 3% (NS) for 30 days, decreased the levels of ALP, AST, and ALT, improved the oxidative damage in liver tissues and attenuated the histological changes in hepatic tissues of C. gariepinus (group 4). Hence, this study suggested that (NS) has hepatoprotective and antioxidant effects in African catfish against AgNPs toxicity.

Acute toxicity and effects of the Roundup Transorb®, a glyphosate-based herbicide, on freshwater teleost matrinxã, Brycon amazonicus

The aim of this study was to evaluate the susceptibility of the Neotropical freshwater fish matrinxa, Brycon amazonicus, exposed to Roundup Transorb®, a newer commercial formulation 50% stronger than the ordinary mixtures and with a new technology for quicker absorption and faster translocation. The median lethal concentration (96 h-LC50) was determined, and the effects of a sublethal concentration on oxidative stress biomarkers were evaluated in the liver, gills, white muscle, and heart. During the acute toxicity test, fish mortality progressively increased with RT concentration along with behavioral abnormalities were detected. The calculated 96 h-LC50 value of RT was found as 1.21 mg/L. Fish exposed to 0.5 mg/L of RT (40% of 96 h-LC50) showed a significant increase in the hepatic somatic index (HSI) with a concomitant decrease in Fulton's condition factor (K). The sublethal exposure also induced significant increases (p < 0.05) in the hepatic lipid peroxidation (LPO) levels, reduced glutathione (GSH) content, and catalase (CAT) activity, with a concomitant decrease in the glutathione S-transferase (GST) activity. In the gills, RT exposure induced significant increases in the GST activity, GSH and LPO levels, whereas CAT activity was inhibited. RT also induced CAT and GST activities together with the content of GSH and LPO levels in the white muscle. On the other hand, significant decreases in the CAT and GST activities were detected in the heart with a marked increase in the GSH content and no changes in LPO levels. Therefore, the exposure to 0.5 mg/L of RT induced oxidative stress in the liver, gills and white muscle with tissue-specific responses related to antioxidant defenses. This study demonstrated that B. amazonicus is sensitive to Roundup Transorb® at sublethal and environmentally relevant concentrations, even at short-term exposures. The use of Roundup Transorb® should be carefully monitored due to its adverse non-target impacts.

Phyllanthin prevents diethylnitrosamine (DEN) induced liver carcinogenesis in rats and induces apoptotic cell death in HepG2 cells

Liver cancer is a critical clinical condition with augmented malignancy, rapid progression, and poor prognosis. Liver cancer often initiates as fibrosis, develops as cirrhosis, and results in cancer. For centuries, medicinal plants have been incorporated in various liver-associated complications, and recently, research has recognized that many bioactive compounds from medicinal plants may interact with targets related to liver disorders. Phyllanthin from the Phyllanthus species is one such compound extensively used by folklore practitioners for various health benefits. However, most practices continue to be unrecognized scientifically. Hence, in this work, we investigated the protective role of phyllanthin on diethylnitrosamine (DEN) induced liver carcinoma in Wistar Albino rats and the anti-tumor potential on human hepatocellular carcinoma (HCC) HepG2 cells. The DEN-challenged liver cancer in experimental rats caused increased liver weight, 8-OHD, hepatic tissue injury marker, lipid peroxidation, and tumor markers levels. Remarkably, phyllanthin counteracted the DEN effect by ameliorating all the liver function enzymes, oxidative DNA damage, and tumor-specific markers by enhanced anti-oxidant capacity and induced caspase-dependent apoptosis through the mTOR/ PI3K signaling pathway. MTT assay demonstrated that phyllanthin inhibited the HepG2 cell growth in a dose-dependent manner. Fascinatingly, phyllanthin did not demonstrate any substantial effect on the normal cell line, HL7702. In addition, HepG2 cells were found in the late apoptotic stage upon treatment with phyllanthin as depicted by acridine orange/ethidium bromide staining. Overall, this work offers scientific justification that phyllanthin can be claimed to be a safe candidate with potential chemotherapeutic activity against HCC.

Beneficial effects of anthocyanin-rich peels of Myrtaceae fruits on chemically-induced liver fibrosis and carcinogenesis in mice

Hepatocellular carcinoma (HCC) arising from fibrosis/cirrhosis is the most common type of primary liver cancer. Conversely, a higher intake of fruits and vegetables might play a protective role in HCC risk. Recently, Myrtaceae family tropical fruits have raised great interest due to the high levels of anthocyanins especially in their peels, which are usually discarded upon consumption. Anthocyanins are antioxidant pigments known to have beneficial effects in vivo/in vitro cancer bioassays. Thus, we evaluated whether dietary Myrciaria jaboticaba, Syzygium cumini, and Syzygium malaccense fruit peel powders reduce fibrosis and hepatocarcinogenesis in mice. Female C3H/HeJ mice were submitted to the model of diethylnitrosamine/carbon tetrachloride-induced liver fibrosis and carcinogenesis. Concomitantly, mice received a basal diet containing 2% of M. jaboticaba, S. cumini, or S. malaccense fruit peel powders, obtained by convective drying, for 10 weeks. M. jaboticaba peel powder showed the highest levels of total anthocyanins, while S. cumini peel powder displayed the greatest diversity of these pigments. All Myrtaceae family peel powders reduced the serum levels of the liver injury marker alanine aminotransferase. M. jaboticaba peel feeding reduced the incidence of liver preneoplastic foci, hepatocyte proliferation (Ki-67), and the protein levels of hepato-mitogen tumor necrosis factor-alpha (TNF-α). M. jaboticaba peel feeding also diminished liver lipid peroxidation and increased total glutathione levels. S. cumini peel feeding reduced hepatic collagen, lipid peroxidation, and TNF-α levels while increased catalase activity. Although S. malaccense peel powder, which displayed the lowest anthocyanin levels, decreased oxidative stress, and cytokine levels, no effects were observed on liver fibrosis or preneoplastic lesion outcomes. Findings indicate a protective effect of anthocyanin-rich M. jaboticaba and S. cumini peel powder feeding on preneoplastic lesion development and fibrosis, respectively. Results indicate that differential biological responses may be attributed to distinct anthocyanin profiles and levels, assigning a functional/market value to the underutilized peel fraction.

Qing-Yu-Mu, an Herbal Formula, Reduces Hepatic Oxidative Stress in Rats Fed a High-Frying Oil Diet and Ameliorates Carbon Tetrachloride-Induced Liver Injury.

Qing-Yu-Mu (QYM) is an herbal formula used to prevent and treat liver disease in Taiwan. In this study, the hepatoprotective effects of QYM were evaluated in two experimental models. First, rats were fed a high-frying oil (FO) diet containing 1.25% QYM for 5 weeks to investigate effects of QYM on hepatic oxidative stress and antioxidant enzyme activities. Then, protective effects of QYM on carbon tetrachloride (CCl4)-induced chronic liver injury were evaluated. Results show that QYM treatment reduced FO diet-induced hepatic lipid peroxidation and reactive oxygen species levels and increased glutathione (GSH) S-transferase activity. A higher reduced GSH/oxidized GSH (GSSG) ratio was observed after QYM treatment. Furthermore, QYM ameliorated CCl4-induced liver injury by reducing the activity of plasma alanine aminotransferase and histological lesions in the liver. QYM also increased the level of hepatic GSH and activities of GSH peroxidase and superoxide dismutase. Finally, chlorogenic acid, chrysophanol, and apigenin were found to be present in relative abundance in QYM. Results show that QYM may exhibit a hepatoprotective effect by reducing oxidative stress and increasing antioxidant activity in the liver.

Dietary supplementation with Gracilaria sp. by-products modulates stress response, antioxidant and immune systems of gilthead seabream (Sparus aurata) exposed to crowding

By-products obtained from seaweed processing appear as a promissory source of bioactive compounds that could be included in aquafeed to improve the sustainability of aquaculture. Therefore, the present study aimed to evaluate the effects of dietary supplementation with by-products obtained from the seaweed Gracilaria sp. on the stress response, antioxidant, and immune systems of gilthead seabream (Sparus aurata) exposed to an acute crowding event. For this, fish were fed six experimental diets: (i) a diet containing a commercial antioxidant (CTR), (ii) a diet without antioxidant addition (NO-AOX), (iii) a NO-AOX diet with 0.5% ethanolic extract (0.5% EE), (iv) a NO-AOX diet with 5% ethanolic waste (5% EEW), (v) a NO-AOX diet with 5% agar waste (5% AW), and (vi) a NO-AOX diet with 2.5% agar waste (2.5% AW) for 59 days. After this period, fish were exposed to 1 h of crowding (100 kg m−3) and sampled immediately after 0 and at 24 h post-crowding. Our results showed that the fish-fed AW and EEW diets showed lower plasma cortisol levels than those fed the CTR diet, suggesting an improved stress response to crowding on these groups. No differences were detected on hepatic lipid peroxidation levels between dietary groups after crowding. However, the fish fed 0.5% EE diet showed lower hepatic glutathione reductase (GR) activity than fish fed the NO-AOX diet. Additionally, glutathione peroxidase (GPx) activity was decreased in the liver of fish fed 2.5% and 5% AW diets compared with the other dietary groups. Concerning immune parameters, the plasma peroxidase activity was higher in fish fed the 2.5% AW diet than fish fed NO-AOX or 5% EEW diets, suggesting a modulatory effect of dietary AW at 2.5% in the humoral immune response in crowded fish. Results suggest that dietary supplementation with AW, particularly when supplemented at 2.5%, could be used as a dietary tool to mitigate oxidative stress when improving immune response in gilthead seabream exposed to a stressor as crowding.

Effects of insulin treatment on hepatic CYP1A1 and CYP2E1 activities and lipid peroxidation levels in streptozotocin-induced diabetic rats.

Reactive oxygen species (ROS) and lipid peroxidation (LPO) levels may increase in diabetic state and lead to oxidative stress, which plays a critical role in the progression of diabetes. There are various sources of ROS, including cytochrome P450 monooxygenases (CYP450s), which may be modulated in terms of their activities and expressions under diabetic conditions. This study is aimed to investigate the effects of streptozotocin-induced diabetes and insulin treatment on hepatic cytochrome P450 1A1 (CYP1A1) and cytochrome P450 2E1 (CYP2E1) activities and LPO levels. Methods: CYP1A1 and CYP2E1 activities were measured with ethoxyresorufin O-deethylase and p-nitrophenol hydroxylase activities, respectively. LPO levels were then corroborated via thiobarbituric acid reactive substances. Results: In diabetic rats, a marked 2.1- and 2.4-fold increase in hepatic CYP1A1 activity and 1.8- and 1.6-fold increase in hepatic CYP2E1 activity were observed compared to controls and insulin-treated diabetic rats, respectively. Hepatic LPO levels in diabetic rats did not significantly change compared to controls. However, in insulin-treated diabetic rats, LPO levels are 0.92- and 0.89-fold remarkably decrease compared to controls and diabetics, respectively. Conclusion: The present study suggests that insulin might have a useful role in the modulation of CYP1A1 and CYP2E1 activities as well as LPO levels in the liver of diabetic rats.

Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis

AbstractAlthough the serum-abundant metal-binding protein transferrin (encoded by the Trf gene) is synthesized primarily in the liver, its function in the liver is largely unknown. Here, we generated hepatocyte-specific Trf knockout mice (Trf-LKO), which are viable and fertile but have impaired erythropoiesis and altered iron metabolism. Moreover, feeding Trf-LKO mice a high-iron diet increased their susceptibility to developing ferroptosis-induced liver fibrosis. Importantly, we found that treating Trf-LKO mice with the ferroptosis inhibitor ferrostatin-1 potently rescued liver fibrosis induced by either high dietary iron or carbon tetrachloride (CCl4) injections. In addition, deleting hepatic Slc39a14 expression in Trf-LKO mice significantly reduced hepatic iron accumulation, thereby reducing ferroptosis-mediated liver fibrosis induced by either a high-iron diet or CCl4 injections. Finally, we found that patients with liver cirrhosis have significantly lower levels of serum transferrin and hepatic transferrin, as well as higher levels of hepatic iron and lipid peroxidation, compared with healthy control subjects. Taken together, these data indicate that hepatic transferrin plays a protective role in maintaining liver function, providing a possible therapeutic target for preventing ferroptosis-induced liver fibrosis.

Protective effects of Allium sativum essential oil rich in disulfides against deltamethrin induced oxidative stress and hepatotoxicity in rats

The purpose of our study was to evaluate the antioxidant potential of Allium sativum essential oil (ASEO) and the protective effects against deltamethrin (D) induced hepatic toxic effects in Wistar rats. Twenty-four male rats were divided into four groups as follows: control, ASEO, D and ASEO + D. Rats were orally gavaged with ASEO (200 mg/kg body weight) and D (7.2 mg/kg body weight) for 4 weeks. The ASEO revealed radical scavenging activity (DPPH) with IC50 = 47.66 ± 2.51 µg/mL, and the lipid peroxidation activity (the β-carotene bleaching method) with IC50 = 0.034 ± 0.007 µg/mL. Analyzed by GC–MS, ASEO confirm that disulfides (38%) and eugenol (15%) were the main components of garlic oil. In terms of in vivo study, deltamethrin exposure induced a significant increase in the biochemical serum parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), hepatic lipid peroxidation (LPO) level, advanced oxidized protein products (AOPP), and carbonyl protein accompanied by decrease in the activities of SOD, CAT, GPX and the levels of GSH (p < 0.01). This toxic effect was confirmed by histological study. The pretreatment with ASEO significantly mended the hepatic toxicity produced by deltamethrin. This finding revealed that ASEO are capable of ameliorating the hepatic oxidative damage induced by deltamethrin.

Protective effects of Sasa veitchii extract on acute ethanol‐induced hepatotoxicity in mice

ABSTRACTAimHigh alcohol consumption leads to alcohol‐related disease. The aim of this study was to explore the effects of Sasa veitchii extract (SE) on ethanol‐induced liver injury.MethodsOf four groups of 7‐week‐old male mice (control, SE, ethanol, and SE + ethanol groups), SE and SE + ethanol groups were orally treated with SE once a day for 3 days. Twenty‐four hours after the last administration, the SE + ethanol and ethanol groups were intraperitoneally injected with ethanol (2 g/kg). The mice in each group were euthanized 24 h after ethanol administration, and blood and livers were collected.ResultsHistopathological examination of the livers of ethanol‐treated mice revealed a depletion of glycogen. Ethanol injection resulted in high plasma levels of alanine aminotransferase and aspartate aminotransferase and high levels of hepatic lipid peroxidation and inflammatory cytokines. Pretreatment with SE reversed all these changes in SE + ethanol mice compared to that in the ethanol group. Moreover, SE injection increased the hepatic protein levels of aldehyde dehydrogenase 2.ConclusionOur results show that SE protected the mice against acute ethanol‐induced hepatic injury by modulating oxidative stress and ethanol metabolism, and hence, could be explored for treatment of alcohol‐related disease.

Curcumin nanoparticles ameliorate hepatotoxicity and nephrotoxicity induced by cisplatin in rats.

The present work was conducted to investigate the effect of curcumin nanoparticles (CUR NPs) on cisplatin-induced hepatotoxicty and nephrotoxicity in rats. Rats were divided randomly into the following: control, rats treated daily with CUR NPs (50mg/kg body wt/day) for 14days, rats treated with a single dose of cisplatin (12mg/kg body wt, i.p), and rats treated with a single dose of cisplatin followed by a daily administration of CUR NPs for 14days. Cisplatin-induced hepato- and nephrotoxicity were evaluated by histological examinations and biochemical analyses of liver and kidney functions. Cisplatin induced significant increases in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and in the levels of bilirubin, urea, uric acid and creatinine. In addition, the levels of hepatic and renal lipid peroxidation (MDA), nitric oxide (NO), and serum tumor necrosis factor-α (TNF-α) increased significantly. However, cisplatin significantly decreased hepatic and renal reduced glutathione levels and renal Na+/K+-ATPase activity. Treatment with CUR NPs ameliorated almost all the biochemical changes induced by cisplatin and improved the histopathological alterations in liver and kidney. In conclusion, the present findings indicate that CUR NPs offered an effective protection against cisplatin-induced hepatotoxicity and nephrotoxicity through its antioxidant and anti-inflammatory properties.

Oxidative stress in liver of grass carp Ctenopharyngodon idella naturally infected with Saprolegnia parasitica and its influence on disease pathogenesis

Fungal diseases are one of the major problems in freshwater fish culture and have been linked to significant losses and high mortality rate, and saprolegniosis caused by Saprolegnia parasitica is the most important oomycete affecting freshwater fish worldwide. The hepatic pathophysiology of infection remains poorly understood and is limited only to histopathological alterations. Thus, the aim of this study was to evaluate whether tissue oxidative damage can be considered a pathway linked to liver damage during S. parasitica infection in grass carp (Ctenopharyngodon idella). Grass carp was divided into two groups (n = 12 per tank, in triplicate), as follows: uninfected group (without cotton-like tuft) used as control; and infected group (with presence of cotton-like tuft; naturally infected with S. parasitica). Hepatic reactive oxygen species (ROS) and lipid peroxidation (LPO) levels were higher in fish naturally infected by S. parasitica compared with uninfected fish, while no significant difference was observed regarding hepatic carbonyl protein levels. Hepatic antioxidant capacity against peroxyl radical (ACAP) levels, as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) activities, was lower in fish naturally infected by S. parasitica compared with uninfected fish. No significant difference was observed between groups regarding glutathione reductase (GR) activity. Histopathological analyses of infected fish revealed generalized cytoplasmic necrosis, and condensation and pyknosis of the hepatocyte nucleus. Based on these evidences, S. parasitica infection elicits oxidative damage via (a) increased ROS production, (b) decreased ROS elimination, and (c) inhibition of enzymatic and non-enzymatic antioxidant defense system. In summary, a disease causes oxidative stress in fish naturally infected, and this oxidative disturbance may contribute directly speed up to disease pathogenesis.

Haloperidol increases hepatic lipid peroxidation promoted by high-fat diet in rats

This study aimed to evaluate the effects of the treatment with haloperidol (HAL) associated with a high-fat diet (HF) on hepatic and renal damage, intracellular magnesium (Mg2+) levels, and abdominal fat content. Young male Wistar rats were fed with high-fat diet or control diet during 48 weeks and, at the 24-week, part of animals began to be co-treated with HAL (1 mg/Kg/day intramuscularly). After 4 weeks of the drug administration, the livers and kidneys were removed for analyses. The results showed that HF diet significantly increased lipid peroxidation in the hepatic tissue of treated animals, when compared to animals treated with control diet (P&lt;0.05). Moreover, HF associated with HAL further increased the hepatic lipid peroxidation levels (P&lt;0.05). In contrast, HF and/or HAL did not promote significant changes in renal lipid peroxidation levels. We also found a negative correlation between intracellular Mg2+ levels and abdominal fat content among all animals. In conclusion, the data presented suggest adverse interactions between HAL and HF on liver. Furthermore, the negative correlation between the intracellular Mg2+ levels and the abdominal fat accumulation suggest a possible involvement of Mg2+ in the metabolic syndrome development associated with a HF diet.