Liver Lipid Peroxidation Levels Research Articles

Investigation on Anti-diabetic Efficacy of a Cucurbitaceae Food Plant from the North-East Region of India: Exploring the Molecular Mechanism through Modulation of Oxidative Stress and Glycosylated Hemoglobin (HbA1c).

The medicinal plants of the Cucurbitaceae family, such as Solena heterophylla Lour. fruits, have significant ethnobotanical value and are readily accessible in North East India. We conducted a study on Solena heterophylla Lour. fruits to evaluate their anti-diabetic activity in vivo, standardize their HPTLC, and profile their metabolites using LC-QTOF-MS. We aimed to explore the molecular mechanism behind their effects on oxidative stress and glycosylated hemoglobin (HbA1c). Firstly, the ethyl acetate fraction of Solena heterophylla Lour. fruits was standardized using Cucurbitacin B as a standard marker by conducting HPTLC evaluation. Next, we delved into analyzing metabolite profiling. In addition, the standardized fraction was utilized in an experimental study to investigate the molecular mechanism of action in an in vivo high-fat diet and a low dose of streptozotocin-induced diabetic model. We have reportedly identified 52 metabolites in the ethyl acetate fraction of Solena heterophylla (EASH). In the in vitro tests, it has been observed that this extract from plants possesses notable inhibitory properties against α-amylase and α-glucosidase. Solena heterophylla fruits with high levels of Cucurbitacin B (2.29% w/w) helped lower FBG levels in animals with EASH treatment. EASH treatment reduced HbA1c levels and normalized liver lipid peroxidation and antioxidant enzyme levels. SGOT, SGPT, and SALP serum enzyme levels also returned to normal. Based on the current evaluation, it was found that EASH exhibited encouraging hypoglycemic effects in diabetic rats induced by a low dose of STZ and high-fat diet, which warrants further investigation.

Hepatoprotective Mechanisms Induced by Spinach Methanolic Extract in Rats with Hyperglycemia-An Immunohistochemical Analysis.

Spinach methanolic extract (SME) has a hepatoprotective effect due to its polyphenolic antioxidants; however, its action in parenchymal (PQ) and non-parenchymal (nPQ) cells remains unknown. This study investigates the hepatoprotective effect of SME on streptozotocin-induced hyperglycemic rats (STZ), focusing on immunohistochemical analyses. Methods: The extract was prepared, and the total polyphenols and antioxidant activity were quantified. Adult male Wistar rats were divided into four groups (n = 8): normoglycemic rats (NG), STZ-induced hyperglycemic (STZ), STZ treated with 400 mg/kg SME (STZ-SME), and NG treated with SME (SME) for 12 weeks. Serum liver transaminases and lipid peroxidation levels in tissue were determined. The distribution pattern and relative levels of markers related to oxidative stress [reactive oxygen species (ROS), superoxide dismutase-1, catalase, and glutathione peroxidase-1], of cytoprotective molecules [nuclear NRF2 and heme oxygenase-1 (HO-1)], of inflammatory mediators [nuclear NF-κB, TNF-α], proliferation (PCNA), and of fibrogenesis markers [TGF-β, Smad2/3, MMP-9, and TIMP1] were evaluated. Results: SME had antioxidant capacity, and it lowered serum transaminase levels in STZ-SME compared to STZ. It reduced NOX4 staining, and lipid peroxidation levels were related to low formation of ROS. In STZ-SME, the immunostaining for antioxidant enzymes increased in nPQ cells compared to STZ. However, enzymes were also localized in extra and intracellular vesicles in STZ. Nuclear NRF2 staining and HO-1 expression in PQ and nPQ were higher in STZ-SME than in STZ. Inflammatory factors were decreased in STZ-SME and were related to the percentage decrease in NF-κB nuclear staining in nPQ cells. Similarly, TGF-β (in the sinusoids) and MMP-9 (in nPQ) were increased in the STZ-SME group compared to the other groups; however, staining for CTGF, TIMP1, and Smad2/3 was lower. Conclusions: SME treatment in hyperglycemic rats induced by STZ may have hepatoprotective properties due to its scavenger capacity and the regulation of differential expression of antioxidant enzymes between the PQ and nPQ cells, reducing inflammatory and fibrogenic biomarkers in liver tissue.

Grewia asiatica fruit extract-based kalari cheese for enhanced storage stability and functional value

The study aimed to develop a functional cheese using Grewia asiatica fruit extract as a novel additive and demonstrated its functional value in oxidative-stress-induced [single dose of CCl4 (1 mL/kg) given intraperitoneally] male Wistar rats. The kalari cheese was developed using buffalo milk containing different levels of the fruit extract (0.0, 0.5, 0.7, and 1.0 %) and an optimum level of 0.7 % was found sensorily. The products (0.0 and 0.7 %) were stored in a refrigerator for 4 weeks and evaluated for storage quality. The extract improved the lipid (TBARS and free-fatty acids) and microbial (total plate and psychrophilic counts) stability and sensory quality of the cheese. The extract-enriched cheese-based diet ameliorated the impact of oxidative stress in the rats during a 4-week feeding trial and significantly (P < 0.05) increased the levels of endogenous antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) and body weight whereas significantly (P < 0.05) reduced the levels of liver marker enzymes (ALT and AST), lipid peroxidation, and relative liver and spleen weights compared to the control. The extract improved the lipid and microbial stability of the cheese and the cheese-based diet ameliorated the effect of oxidative stress in rats, indicating the functional value of the developed product.

Potent In Vitro and In Vivo Effects of Stachys lavandulifolia Methanolic Extract against Toxoplasma gondii Infection.

MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to evaluate the in vitro effect of the SLME on T. gondii tachyzoites. Totally, 72 male BALB/c mice (40 mice for in vivo evaluation of SLME and 32 mice for its toxicity effects on liver and kidney serum enzymes) were used for the present investigation. At first, 40 mice were orally pre-treated with the SLME at doses of 25, 50, and 75 mg/kg/day for two weeks. Mice were checked daily, and the rate of survival and the mean number of tachyzoites were recorded. Liver lipid peroxidation (LPO) and nitric oxide (NO) levels, the effects on kidney and liver function, as well as the expression level of the proinflammatory cytokines such as interleukin-1β (IL-1β) and interferon-γ (IFN-γ), were studied by the quantitative real-time PCR. Flow cytometry analysis was performed on the effects of SLME on the detection of apoptotic and necrotic cells in T. gondii tachyzoites. The SLME at the concentrations 75 and 150 µg/mL completely killed the tachyzoites after 2 hr of incubation. SLME at 25, 50, and 75 mg/kg/day increased the survival rate of infected mice by the sixth, seventh, and eighth days, respectively. SLME also significantly (p < 0.05) decreased the LPO and NO levels and upregulated the IL-1β and IFN-γ mRNA gene expression levels, whereas no considerable change was observed in the serum level of kidney and liver enzymes. Flow cytometry analysis revealed the prompted early and late apoptosis after exposure to T. gondii tachyzoites with various concentrations of SLME. We found the relevant in vitro anti-Toxoplasma effects of SLME against T. gondii. Moreover, the results confirmed the promising in vivo prophylactic effects of SLME. SLME provokes the innate immune system, induces apoptosis, modulates the proinflammatory cytokines, and inhibits hepatic injury in infected mice. With all these descriptions, further surveys are required to support these findings and elucidate this plant's possible mechanisms of action.

Stress response of European seabass (Dicentrarchus labrax) fed plant-based diets supplemented with swine blood hydrolysates

To improve fish welfare, it is essential that aquafeeds are designed to help fish cope with the stressful conditions of fish farms. One effective strategy to achieve this goal is to supplement the diet with bioactive hydrolysates. Here, diet supplementation to modulate oxidative stress after air exposure was investigated in European seabass, using swine blood hydrolysates (BH), obtained either by autohydrolysis (AH) or enzymatically. The enzymatically produced BH were further submitted to a micro- (RMF) and nanofiltration (RNF). Four isolipidic, isoproteic and isoenergetic diets were developed: a plant-based diet with low (12.5%) fishmeal levels (control, CTRL) and three diets where 3% of each BH (RMF, RNF and AH) was added to the CTRL. Diets were assigned to triplicate groups of 71 European seabass juveniles (initial weight 12.3 ± 1.4 g). After 12 weeks, 9 fish per treatment were either immediately sampled or air-exposed for 1 min and let to recover in a new system for 6 h prior to sampling. Stress response increased cortisol levels, followed by an increment in plasma lactate. The challenge increased liver lipid peroxidation (LPO) due to reactive oxygen species (ROS) accumulation. Carbonyls decreased post-stress, maybe due to a possible interaction with the LPO radicals, reducing protein oxidation. None of the BH improved plasma stress response. By reducing catalase levels without increasing LPO, the RNF treatment appears to adjust European seabass' antioxidant defences, indicating its potential to supply exogenous antioxidants to combat oxidative stress induced by ROS. However, this impact was not sufficient to lower LPO levels compared to a control plant-based diet. The tested diets seemed to affect the fish oxidative stress response in the liver, possibly due to the presence of bioactive peptides, which aided in the non-enzymatic modulation of stress response, as observed by the total antioxidant capacity values in the liver.

Quercetin Zinc and Iron Metal Complexes Protect against Sodium Arsenite Intoxication in the Hepato-Renal System of Wistar Rats via the Oxidative Stress Pathway.

Chronic exposure to arsenic is a major health concern consequent upon generation of excessive reactive oxygen species. The safety of treatment with chelating agents has not been well established; therefore, there is a need for a paradigm shift in the approach to management of arsenic toxicity. Bioflavonoids are known to influence redox homeostasis in cells; the study therefore investigates the efficacy of quercetin and its zinc and iron metal complexes on sodium arsenite (NaAr)-intoxication in rats. Spectroscopic study of quercetin hydrate and its metal complexes was performed using UV-Vis and FT-IR spectrometer. Furthermore, twenty male Wistar rats were obtained and equally divided into four groups, treated orally and daily for 28 days with 10 mg/kg NaAr, 30 mg/kg quercetin, quercetin-zinc, and quercetin-iron separately. Five more rats were used as control. Plasmatic aspartate transferase (AST), alanine transferase (ALT), creatinine (CREA), and total protein (TP) were estimated. Levels of kidney and liver lipid peroxidation (LPO), glutathione (GSH), catalase (CAT), and glutathione-S-transferase (GST) were determined. Histology was used to view the lesions. Treatment of arsenic-toxicity with quercetin and its complexes decreased the activities of ALT, AST, CREA, TP, CAT, and GST and concentration of LPO and GSH. Quercetin-zn treatment showed a better result than quercetin-iron in the liver. Histology results showed absence of lesions in quercetin zinc and iron treatment in both the kidney and the liver. Quercetin zinc and iron increased the bioavailability of quercetin and therefore could be relevant as adjuvants in arsenic poisoning.

Short term deuterium depletion in drinking water reduced tumor induced oxidative stress in mice liver.

The aim of current work was able to show the oxidant effect of cancer cells found in any part of the body on the liver and to investigate the possible protective effect of deuterium-depleted water (DDW) on this oxidant effect by determining of some liver parameters. Ehrlich ascites tumor bearing BALB/c mice were used for this purpose. BALB/c mice were selected randomly and divided into four groups (n=5 in each group) as control group, tumor group, control+DDW group, tumor+DDW group, fifteen days after tumor cell injection, liver tissue samples were taken for all groups. In the tumor group, liver lipid peroxidation, sialic acid and protein carbonyl levels, xanthine oxidase, myeloperoxidase, catalase, gamma-glutamyl transferase, sorbitol dehydrogenase, glutathione peroxidase and glutathione reductase activities, were significantly higher than those in the control group while glutathione levels and paraoxonase1, sodium potassium ATPase, glutathione-S-transferase, alanine transaminase and aspartate transaminase activities decreased significantly. Compared with the tumor group, the changes in all parameters except sialic acid, catalase, alanine transaminase and aspartate transaminase were reversed in the DDW given tumor groups, while sialic acid and catalase values continued to increase, and alanine transaminase and aspartate transaminase values continued to decrease. In conclusion, the consumption of DDW may be beneficial and protective against excessive oxidative stress in cancer complications.

Effects of white mustard (Sinapis alba) oil on growth performance, immune response, blood parameters, digestive and antioxidant enzyme activities in rainbow trout (Oncorhynchusmykiss)

A study was conducted to evaluate the effects of dietary supplementation of white mustard (Sinapis alba) oil (WMO) on growth performance, immune responses, digestive and antioxidant enzyme activities in juvenile rainbow trout (Oncorhynchus mykiss). For this purpose, fish (initial weight: 25.77 ± 0.13 g) were divided into four experimental groups in triplicate and fed ad libitum twice a day with diets containing WMO at 0 (control), 0.5, 1, and 1.5% of diet for 9 weeks. Three fish from each tank (n:9 per treatment) were sampled on 21st, 42nd, and 63rd days for further analyses. At the end of the feeding period, fish were challenged with Aeromonas hydrophila and Yersinia ruckeri in two separate experimental setups. Results showed that final weight, weight gain, and specific growth rate were significantly increased in all experimental groups compared to the control. Feed conversion ratio was similar among treatments. Respiratory burst and potential killing activity decreased in all experimental groups compared to the control (P < 0.05). Lysozyme and myeloperoxidase activities were elevated in all experimental groups at the end of the experiment compared to the control (P < 0.05). Cytokine gene expressions in the head kidney and intestine were elevated in all experimental groups compared to that of the control in general (P < 0.05). Hematological responses of the experimental fish groups were similar to that of the control (P > 0.05). Pepsin and trypsin levels decreased in all experimental groups (P < 0.05). In terms of antioxidant enzyme activities, significant improvement in liver superoxide dismutase, catalase, and glutathione s-transferase activities in all treatment groups were determined (P < 0.05). In addition, a significant decline in liver lipid peroxidation levels was recorded in all treated groups at all sampling times compared to the control (P < 0.05). At the end of this feeding trial, no significant differences (P > 0.05) were observed in survival against A. hydrophila among experimental groups compared to the control (P > 0.05). However, increased survival against Y. ruckeri was determined in experimental fish groups (P < 0.05). This study suggests that white mustard oil had a favorable effect on the overall health and growth of rainbow trout.

Modulatory efficacy of Punica granatum L. powder ethanol extract (PLEE) on lead acetate-induced hepatic and renal toxicity

BackgroundPomegranate powder derived from pomegranate fruit contains phytochemicals chief of which is ellagitannins. Owing to their high antioxidative capabilities we investigated its efficacy against lead acetate induced hepatic and renal toxicity.MethodsPomegranate powder (500 g) was procured and soaked in 1 Litre of ethanol for three days, its filtrate was concentrated and freeze dried to form Punica granatum L. ethanol extract (PLEE). Thirty (30) male albino Wistar rats with average weight between 140 ± 20 g were used for this study. They were equally shared into 6 groups with 5 animals each; A: Control; B: Lead acetate only C: Lead acetate + PLEE (1); D: Lead acetate + PLEE (2); E: PLEE (1) and F: PLEE (2). Serum, liver and kidney samples were obtained for biochemical assays. The integrity of liver and kidney tissues were also accessed.ResultsLead administration resulted in marked elevations in liver transaminases in serum and liver as well as a significant increase in kidney function markers in the serum and kidney (p < 0.05). There was also a significant decline in average body weight, antioxidant markers in the liver and kidney of Wistar rats while there was a significant increase in lipid peroxidation levels in both liver and kidney. However, administration of PLEE at different doses significantly modulated these changes.ConclusionLead acetate administration led to hepatic and renal toxicity as evident by alterations in liver and kidney function markers, antioxidant status and tissue integrity. However, PLEE can combat these toxicities.

Metabolite Profiling of Peltophorum africanum Sond. & Saraca indica L. Leaves via HR-UPLC/PDA/ESI/MS Analysis and Assessment of their Anti-Diabetic Potential

This study aimed to screen different extracts (E) such as total ethanol (TE), petroleum ether (PE) chloroform (CH), ethyl acetate (EA) and methanol (AM) extracts of Peltophorum africanum Sond. (PA) and Saraca indica L. (SI) leaves (family fabaceae) for their in-vitro antidiabetic activity using α-amylase inhibition assay. The extracts that showed remarkable in vitro activity were further subjected to in vivo anti-diabetic assessment using streptozotocin-induced diabetes model in experimental animals where serum glucose, C-peptide, liver glycogen content in addition to lipid peroxide level in both serum and liver were estimated biochemically in normal and diseased rats. The average percent of weight change and kidney to body weight ratio percent were calculated for all animal groups. Histopathological examination of pancreas, liver and kidney sections isolated from all animals was carried out. UPLC/MS/MS analysis of TEE of PA and SI for chemical investigation was performed. Results of the in vitro anti diabetic activity revealed that EAE, PEE& TEE of PA and TEE & EAE of SI possessed the highest inhibitory activity as compared to acarbose. In vivo antidiabetic activity of the selected extracts revealed that animal groups treated daily with EAE of PA and SI exhibited a significant improvement in carbohydrate metabolism and lipid peroxide level, with superior effect in comparison with that of TEE and PEE of both plants. Histopathological findings showed marked protection particularly in sections isolated from animals treated with EAE of PA. UPLC/MS/MS analysis of TEE of both plants identified 46 metabolites belonging to various classes. It could be suggested that active extracts of both plants could be considered as potential natural antioxidant and anti-diabetic agents.

Attenuation of oxidative damage-associated hepatotoxicity by piperine in CCl4-induced liver fibrosis

ObjectivesThe present research has demonstrated the impact of treatment with piperine on hepatic fibrosis induced by the administration of carbon tetrachloride. MethodsIn order to study the outcome of piperine treatment on hepatic fibrosis caused by carbon tetrachloride administration in male Wistar rats, a total of 24 rats were collected and randomly classified into 4 separate groups each consisting of 6 animals. Group I was assigned as a controlgroup and treated with olive oil for 4 weeks (1 ml/kg, i.p.) with two doses each week. Group II was designated as a toxic group and treated with carbon tetrachloride for 4 weeks (1 ml/kg, 1:1 combination with olive oil, i.p.) with two hepatic fibrosis induction doses each week. Group III was graded as a group I therapy and co-treated with carbon tetrachloride (1 ml/kg, 1:1 combination with olive oil, i.p.) for 4 weeks with two hepatic fibrosis induction doses a week and with piperine (25 mg/kg) for 4 weeks. Group IV was designated as group II therapy and co-treated with carbon tetrachloride (1 ml/kg, 1:1 combination of olive oil, i.p.) for 4 weeks with two hepatic fibrosis induction doses a week and piperine (50 mg/kg) for 4 weeks. ResultsPiperine significantly reduced the carbon tetrachloride augmented activities of liver enzymes, lipid peroxidation, glutathione, hydroxyproline, nitrite, and carbonyl levels. Carbon tetrachloride enhanced Total cholesterol (TC), Triglyceride (TG), Low density lipoprotein (LDL), and Very low density lipoprotein (VLDL) levels, and decreased High density lipoprotein (HDL) level was restored to normal with piperine treatment. Moreover, piperine inhibited the over-expression of pro-inflammatory biomarkers and α-SMA. ConclusionThe data of the current study demonstrated piperine as a potent hepato-protective agent and recommends the use of piperine for preventing hepatic fibrosis.

Effects of date seeds administration on anxiety and depressive symptoms in streptozotocin-induced diabetic rats: biochemical and behavioral evidences.

Several epidemiological data indicate that chronic hyperglycemia is associated with behavioral changes such as anxiety and depressive symptoms. Date seeds, one of the most potent products with potential antioxidant activities and possess many benefits against hyperglycemia and its complication. The aim of the current study was to explore the potential effect of date seeds extract on biochemical and behavioral changes (anxiety and depression) in streptozotocin (STZ)-diabetic rats. Rats were divided into four groups as follows: normal control, diabetic control, diabetic treated with the lyophilized aqueous extract of the date seed (2,000mg/kg) (LAE-DS) and diabetics treated with insulin (4UI/day). Experimental diabetes was induced by a single intraperitoneal injection of STZ (60mg/kg). After 24days treatment period, anxiety and depressive behaviors were evaluated using four behavioral tests. After sacrifice, blood samples were collected to evaluate lipid parameters. In addition, rat organs (kidney, liver and brain) were dissected out in order to estimate lipid peroxidation levels as oxidative stress marker. Oral administration of the lyophilized aqueous extract of date seeds and insulin injection for 30days significantly decreased blood glucose levels in STZ-diabetic rats and protected them against undesirable changes in lipid parameters, including cholesterol, triglycerides, LDL cholesterol, VLDL cholesterol and atherosclerosis index. Compared to untreated diabetic rat, a significant decrease in lipid peroxidation levels in kidney, liver and brain (Hippocampus and prefrontal cortex) were observed after treatment with insulin or LAE-DS in diabetic rats. Furthermore, insulin and LAE-DS administration prevented anxiety-related behaviors in STZ-diabetic rats. Therefore, it would be possible to combine this extract with insulin and use it as an antioxidant supplement for type 1 diabetic patients.

Comparison of the Histopathological Effects of Selenium Nanoparticles and Cerium Oxide Nanoparticles in Cadmium-intoxicated Rabbits

This study compared the effects of selenium nanoparticles and cerium oxide nanoparticles on biochemical and histopathological changes of cadmium-intoxicated rabbits. Forty white New Zealand rabbits were equally distributed into four groups. The Control group received saline orally while the negative control group received six-week oral administrations of cadmium 5 mg/kg. The third group received oral administration of selenium nanoparticles (0.8 mg/kg) and cadmium (5mg/kg). The fourth group received cerium oxide nanoparticles (0.8 mg/kg) and cadmium (5mg/kg). After six weeks, serum was obtained by the conventional methods, and then rabbits were sacrificed to obtain liver, kidney, and testis tissues for histopathological examinations. The oral administrations of Cadmium 5 mg/kg caused significant elevations in serum liver enzyme levels, serum BUN, serum creatinine, and lipid peroxidation levels (P&lt;0.05). The histopathological investigations showed necrosis and inflammations in the liver, kidney, and testis of rabbits. Selenium nanoparticles oral administrations at a dose of 0.8 mg/kg significantly reduced liver enzymes, malondialdehyde (MDA) content, and histopathological changes. The cadmium intoxicated rats treated with Cerium oxide nanoparticles showed normal biochemical and histopathological parameters (P&lt;0.05). The current study proved the hepatoprotective and nephroprotective effects of selenium nanoparticles and cerium oxide nanoparticles in cadmium intoxicated rabbits; however, cerium oxide nanoparticles were more effective.

Targeting PI3K/Akt/Nrf2 pathway by glabridin alleviates acetaminophen-induced hepatic injury in rats

Acetaminophen (APAP) induced liver injury is a leading cause for drug-induced liver damage. Glabridin is an isoflavonoid that is reported to possess anti-inflammatory and oxidative stress preventing effects. The aim of this study was to evaluate the protective effects of glabridin against APAP-induced liver injury in rats. Rats were pre-administered with glabridin (30 mg/kg, p.o.; 7 days) followed by single dose of APAP (500 mg/kg, i.p.; 7th day) one hour after glabridin administration. The resulting levels of liver enzymes (AST, ALT, ALP), lipid peroxidation, antioxidant enzymes (CAT, GPx, SOD, GST), reduced glutathione (GSH), inflammatory mediators (TNF-α, IL-6, IL-1β), and apoptosis regulator proteins (casp-3, casp-9, Bcl2, Bax) were determined. Oxidative stress, inflammation and apoptosis triggered due to APAP-induced liver injury were significantly alleviated (p < 0.05) by glabridin. Western blot analysis showed the regulatory effect of glabridin on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and Nrf2/HO-1 protein expressions against APAP-induced toxicity. Histopathological (H&E) data provided evidence for the protective effect of glabridin on rat liver tissue from injury caused by APAP. In conclusion, the protective effect of glabridin on APAP-induced liver injury was exerted by activating the PI3K/Akt/Nrf2/HO-1 pathway, inhibiting oxidative stress, inflammation, and apoptosis.

Antioxidant, anti-cancer and ameliorative activities of Spirulina platensis and pomegranate juice against hepatic damage induced by CCl4

Due to the excessive impact of synthetic drugs, unravelling and employing safe, natural alternatives are now needed to resolve a number of diseases. In this research, we have evaluated hepatoprotective and antioxidant activities of Spirulina platensis and pomegranate juice in rats against hepatotoxicity induced by carbon tetrachloride (CCl4). Spirulina crude carotenoid extract was screened by UPLC-MS / MS. Activities of liver marker enzymes; measured aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and determined lipid peroxidation and antioxidant status as reduced glutathione (GSH) in liver homogenate. The infusion of CCl4 (2 ml/kg b.wt) greatly increases levels of liver marker enzymes and lipid peroxidation, resulting in depletion of antioxidants. Treatment of Spirulina platensis (Sp), pomegranate juice (Pj)or mixture (PJSP) of Spirulina water extract 10% and pomegranate juice 90% (1 ml/100 g b.wt) to CCl4-disrupted rats resulted in decreased activity of liver marker enzymes, lipid peroxidation with increased antioxidant status. Chromatographic separation showed that ß-carotene is the predominant carotenoid extract. This carotenoid extract was tested for colon carcinoma (HCT-116), liver carcinoma (HepG2) and intestinal carcinoma cell lines (CACO) LC50 for 21.8, 14 and 11.3 ug / ml, respectively. Total phenolic phytochemicals, total carotenoids and total flavonoids were also measured in Spirulina. Our study clearly demonstrates that Spirulina platensis and pomegranate juice had hepatoprotective effect on CCl4-caused hepatotoxicity in rats through its antioxidant activity.

A biochemical approach to the anti-inflammatory, antioxidant and antiapoptotic potential of beta-carotene as a protective agent against bromobenzene-induced hepatotoxicity in female Wistar albino rats.

Bromobenzene is a compound which has contributed much in understanding the mechanisms involved in xenobiotic hepatotoxicity induced by drugs and environment pollutants. In the present study, the protective and ameliorative effect of beta-carotene was investigated against bromobenzene-induced hepatotoxicity and compared with silymarin, a standard hepatoprotective reference drug. Beta-carotene (10 mg/kg b.w. p.o.) was administered to the rats for 9 days before intragastric intubation of bromobenzene (10 mmol/kg b.w.). Liver marker enzymes (aspartate transaminase, alanine transaminase and alkaline phosphatase), total protein content, bilirubin, total cholesterol, high-density lipoproteins, triglycerides, antioxidant status (reduced glutathione, superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase) were assessed along with histopathological analysis. ELISA was performed for analysing the levels of cytokines such as TNF-α, IL-1β and IL-6 in serum and in the liver. Caspase-3, COX-2 and NF-κB were evaluated by Western blotting. Administration of bromobenzene resulted in elevated levels of liver marker enzymes, bilirubin, lipid peroxidation and cytokines but deterioration in total protein content, antioxidant levels and histopathological conditions. Pre-treatment with beta-carotene not only significantly decreased the levels of liver markers, lipid peroxidation and cytokines but also improved histo-architecture and increased antioxidant levels minimising oxidative stress, and reduced factors contributing to apoptosis. This significant reversal of the biochemical changes on pre-treatment with beta-carotene in comparison with rats administered with bromobenzene clearly demonstrates that beta-carotene possesses promising hepatoprotective effect through its antioxidant, anti-inflammatory and antiapoptotic activity and hence is suggested as a potential therapeutic agent for protection from bromobenzene.

Thyme oxymel by improving of inflammation, oxidative stress, dyslipidemia and homeostasis of some trace elements ameliorates obesity induced by high-fructose/fat diet in male rat

ObjectiveThyme oxymel is a mixture of vinegar, sugar and thyme which is traditionally used in many folk medicines as syrup to treat metabolic disorders. The molecular mechanisms of anti-hyperlipidemic and anti-inflammatory and antioxidant effects of thyme oxymel or oxymel and its role on homeostasis of trace elements are not fully understood. The aim of this study was to evaluate the anti-inflammatory, antioxidant and anti- hyperlipidemic effects of different doses of thyme oxymel and oxymel on obesity induced by high-fat/-fructose diet (HFFD) in male rat. MethodsEighty adult male Sprague-Dawley rats were randomly divided into eleven groups and treated daily for 24 weeks. At the end of the study, serum levels of liver enzymes, lipid profiles, blood glucose, insulin, antioxidant enzymes and lipid peroxidation and TNF-α were measured. The hepatic oxidative biomarkers and the genes expression of SREBP-1c, CPT-1, Nrf-2 and NF-κB were also studied to determine the molecular mechanism involved in this disease. ResultsThe results showed that HFFD could significantly change the level of oxidative biomarkers, lipid profiles, TNF-α, liver enzymes, leptin, insulin and the levels of some trace elements in obese rats compared to control group (p < 0.05), while pretreatment and treatment with thyme oxymel and oxymel in obese rats could significantly ameliorate them and bring some of them back to normal (p < 0.05).The molecular results also showed that HFFD significantly up-regulated the expression of SREBP-1c and NF-κB and down-regulated CPT-1 and Nrf-2 expression(p < 0.05). While, pretreatment and treatment with thyme oxymel or oxymel in obese rats could significantly ameliorate them (p < 0.05). ConclusionsIt can be concluded that thyme oxymel or oxymel can alleviate HFFD-induced obesity through improving oxidative stress, inflammation, lipid metabolism, homeostasis of some trace elements, and weight-regulating hormones.

In vitro antioxidant activity and protective effect of Hertia cheirifolia L. n-butanol extract against liver and heart mitochondrial oxidative stress in rat

Abstract The current study investigated the protective effect of Hertia cheirifolia L. n-butanol extract on oxidative stress in vitro by measuring lipid peroxidation (MDA) level and superoxide anion (O2 •-) production in liver and heart mitochondria of rat. In addition, the antioxidant potential of H. cheirifolia n-butanol extract was evaluated by using five methods: ABTS•+, O2 •-, Bleaching of β-carotene in linoleic acid, CUPRAC and Ferric reducing power. The results indicated that n-butanol extract contained large amounts of total phenolics (203.52±1.81 mg GAE/g) and flavonoids (104.86±0.57 mg QE/g), and had an interesting antioxidant activity and protective effect on mitochondrial oxidative stress. Therefore, H. cheirifolia n-butanol extract may serve as potential source of natural antioxidant for pharmaceutical applications.

Benzoquinone derivatives with antioxidant activity inhibit activated hepatic stellate cells and attenuate liver fibrosis in TAA-induced mice

Liver fibrosis is a common pathological consequence of liver injury, which increases liver failure-related morbidity and mortality. Hence, anti-fibrotic treatment is urgently needed. Oxidative stress plays a pivotal role in the progression of liver fibrosis. Thus, targeting ROS may be an effective strategy for liver fibrosis treatment. In this study, we investigated four benzoquinones derivatives, including 5-isopropyl-2-methyl-1,4-benzoquinone (TQ), 2-tert-butyl-1,4-benzoquinone (tBu-Q) 2,5-dimethyl-p-benzoquinone (Dime-Q) and p-benzoquinone (Ph-Q), as well as the evaluation of their antioxidant activity and anti-fibrotic effects on activated hepatic stellate cells and TAA-induced mice. Electrochemical analysis showed that all compounds possessed antioxidant property. The result was first confirmed by in vitro experiments, which revealed potential anti-fibrotic activity of all four compounds at the cellular level. Benzoquinone derivatives act as ROS-scavenging molecules, which modulated the TLR4-CD14 signaling pathway to inhibit the expression of procaspase-1 and IL-1β in cells, induced apoptosis via a mitochondrial pathway by upregulating the ratio of Bax/Bcl-2 and by activating caspase-3, as well as inhibited the expression of the anti-apoptotic proteins FLIP and XIAP in activated LX-2 cells. In addition, a TAA (Thioacetamide)-induced mouse model was used to further validate the results. Treatment with benzoquinone derivatives significantly decreased the levels of liver injury markers and lipid peroxidation caused by excessive ROS, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA). Moreover, treatment with benzoquinone derivatives significantly inhibited extracellular matrix (ECM) deposition and downregulated the mRNA and protein expression of liver fibrosis markers, such as collagen I, alpha-smooth muscle actin (α-SMA), and TIMP-1. In summary, these results indicate that benzoquinone derivatives may act as potential therapeutic drugs against liver fibrosis.

In vitro and in vivo analysis of the anti-plasmodial activity of ethanol extract of Phyllanthus nivosus W. Bull leaf.

Antimalarial agents are necessary tools in the global malaria eradication agenda and plants used traditionally in the treatment of malaria are indispensable sources of antimalarial compounds. The aim of this study was to evaluate the antiplasmodial potential of Phyllanthus nivosus leaf. In vitro antiplasmodial assay was conducted using Plasmodium falciparum infected erythrocytes incubated at 37°C in modified RPMI 1640 culture media. The inhibitory effect of the ethanol extract on plasmodium lactate dehydrogenase (pLDH) activity was determined as a measure of antiplasmodial activity. In vivo study was done using mice infected with chloroquine sensitive P. berghei (NK-65 strain). Parasitemia, packed cell volume (PCV), hemoglobin (Hb) and liver lipid peroxidation (MDA) levels were determined after a 4day treatment. Chloroquine was used as standard drug for both assays. The extract reduced pLDH activity by 39.52, 42.07 and 43.87% at 12, 25 and 50μg/mL respectively. 100 and 200mg/kg body weight of extract and 10mg/kg chloroquine suppressed parasitemia of infected mice by 82.76, 81.11 and 86.87% respectively. Furthermore, the extract significantly reduced (p < 0.05) the elevated MDA level and reversed PCV and Hb levels of infected mice to normal values. Phytochemical screening of the extract revealed the presence of alkaloids, tannins, flavonoids, cardiac glycosides, anthraquinones, steroids and terpenes. Gas chromatography-mass spectrometry (GC-MS) analysis showed the presence of ten compounds, the most abundant of which is Methyl linoleate (35.77%). This study demonstrated that P. nivosus leaf possesses antimalarial potential and contains bioactive compounds that could be beneficial in the development of new antimalarial agents.