Oxidative Damage In Hepatic Tissues Research Articles

The effects of pioglitazone and rosiglitazone on liver function in hypothyroid rats.

This study aimed to investigate the antioxidant effect of rosiglitazone (ROG) and pioglitazone (POG) on oxidative damage and dysfunction of hepatic tissue in hypothyroid rats. The male rats were classified into six groups: (1) Control; (2) Hypothyroid, (3) Hypothyroid-POG 10, (4) Hypothyroid-POG 20, (5) Hypothyroid-ROG 2, and (6) Hypothyroid-ROG 4. To induction hypothyroidism in rats, propylthiouracil (PTU) (0.05 %w/v) was added to drinking water. In groups 2-6, besides PTU, the rats were also intraperitoneal administrated with 10 or 20 mg/kg POG or 2 or 4 mg/kg ROG for six weeks. Finally, after deep anesthesia, the blood was collected to measure the serum biochemical markers and hepatic tissue was separated for biochemical oxidative stress markers. Administration of PTU significantly reduced serum thyroxin concentration, total thiol levels, activity of superoxide dismutase (SOD) and catalase (CAT) enzymes, and increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (Alk-P) and malondialdehyde (MDA) in the liver. Additionally, our results showed that prescription of POG or ROG for six weeks to hypothyroid rats resulted in an improvement in liver dysfunction (decrease in serum levels of AST, ALT, and ALK-P) through reducing oxidative damage in hepatic tissue (increase in CAT, SOD, or total thiols and decrease in MDA levels). The findings of the present study presented that the IP administration of POG and ROG for six weeks improves liver dysfunction induced by hypothyroidism in juvenile rats by reducing oxidative damage.

Protective effect of flaxseed oil the on diazinon-induced hepatotoxicity in male rats

Here in, we investigated the possible hepatoprotective effects of flaxseed oil on Diazinon (DZN) induced oxidative stress in rat liver. Twenty-five adult male Wistar rats (180–200 g) were divided randomly into five groups: Control group (1 ml normal saline orally), DZN group (70 mg/kg/day, p.o.), flaxseed oil group (200 mg/kg/day, p.o.), and co- treatment groups (DZN 70 mg/kg/day plus flaxseed oil at doses of 100 and 200 mg/kg/day, respectively). Oxidative stress markers including liver and serum level of malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (TAC), and total thiol group (TTG) were analyzed. Also liver function tests such as serum Alanine aminotransferases (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) were evaluated. Hematoxylin and eosin (H&E) staining was used for liver histological study. Compared to control group, DZN significantly increased liver and serum level of MDA, CAT, TAC and TTG. Also, DZN increased serum ALT, AST, and ALP levels. Flaxseed oil consumption significantly improved oxidative stress status and liver functions tests. Theses effectiveness was completely dose dependent. Also, flaxceed oil ameliorates liver histopathological alterations induced by DZN. Our data demonstrated DZN induced liver toxicity through oxidative stress mechanisms. Flaxceed supplementation had liver protective effects by decreasing oxidative stress markers and improvement of antioxidative status. Also, flaxceed reduced the development of DZN-induced alterations in liver. It seems that flaxceed supplementation may have protective role in DZN-induced oxidative damage in hepatic tissues.

Hepatic susceptibility to oxidative damage after repeated concomitant exposure to aspartame and aflatoxin B1 in rats

The potential interactions among food additives/contaminants and the consequences to biological systems is a topic that is rarely addressed in scientific literature. Thus, the current study investigated if the combined administration of ASP and AFB1 would impair hepatic and renal oxidative status. Male Wistar rats received during 14 days once a day ASP (75 mg/Kg) and/or AFB1 (250 µg/Kg) through intragastric route. At the end of experimental protocol, samples of liver and kidneys were collected for assessing biochemical markers of oxidative status. In the hepatic tissue, the treatment with a single substance (ASP or AFB1) caused an increase in TBARS levels, and a reduction in non-enzymatic antioxidant defenses (Vit C and NPSH levels and FRAP test). In the kidneys, TBARS levels were increased only in the group that received ASP + AFB1. The association reduced NPSH content, while the treatment with AFB1 reduced the FRAP levels. GST and CAT activities were increased in all treatments. Overall, ASP and AFB1 association presented higher toxic effects to the tissues. To the best of our knowledge, this is the first study demonstrating that the associated use of both ASP and AFB1 induces more extensive injuries in comparison to the effects caused by each one alone. Therefore, these data demonstrated that concomitant exposure to ASP and AFB1 potentiated their oxidative damage in hepatic tissue, suggesting that this organ is particularly sensitive to the toxic action induced by these substances.

Optimization, characterization and hepatoprotective effect of polysaccharides isolated from Stipa parviflora Desf. against CCl4 induced liver injury in rats using surface response methodology (RSM).

The roots of Stipa species have been used for treatment and prevention of a various number of diseases. To the best of my knowledge, little information is regarding the antioxidant and hepatoprotective activities of polysaccharides from Stipa parviflora (SPP). Hence the polysaccharides from this plant sample have been investigated here. In addition, Box-Behnken design and response surface methodology were used to optimize the hot extraction conditions. The optimal conditions were determined as: extraction time 120 min, extraction temperature 70 °C and ratio of water to raw material 30. Crude SPP was composed of mannose, ribose, glucose, galactose, pyranose and arabinose. In addition, the SPP showed a strong antioxidant capacity in vitro. In vivo experiments showed that CCl4 treatment caused significant oxidative damage in hepatic tissues, whereas these problems were inhibited by SPP treatment. Hepatoprotective potential of SPP was evaluated by estimating the levels of serum markers like ALT and AST levels. SPP treated rat liver anti-oxidant parameters (SOD, CAT and GPx) were significantly antagonized for the pro-oxidant effect of CCl4. Histopathological studies proved that the SPP extract has significant hepatoprotective activity. In conclusion, the SPP fraction isolated from S. parviflora showed significant hepatoprotective potential which could be related to active compounds present in this fraction.

Histopathological changes and oxidative damage in hepatic tissue of rats experimentally infected with Babesia bigemina.

The present study was aimed to investigate oxidative stress, DNA damage, and histopatholog- ical alterations in hepatic tissues of splenectomized Wistar rats experimentally infected with Ba- besia bigemina. Rats were challenged with 5x106 infected erythrocytes. Babesia infection was con- firmed both with Giemsa's staining blood smears and nested-PCR amplified region of apical membrane antigen-1 (AMA-1) gene. Parasitemia reached approximately 10 % at day 5 post-in- fection. Livers of infected rats were enlarged and darker in color, became extremely brittle with marked congestion. Microscopic evaluation showed cytoplasmic clearing of hepatocytes and se- vere hydropic changes with significantly dilated sinusoids containing macrophages and also intra- sinosoidal parasitized erythrocytes. Severe infiltration of lymphoplasma cells was also present throughout the liver parenchyma. Furthermore, Kupffer cells were enlarged and, occasionally, containing Babesia-parasitized erythrocytes. The activity of Glutathione (GSH) and catalase (CAT), and total antioxidant capacity (TAC) were also significantly decreased (p ⟨ 0.05) after infection of rats with B. bigemina. B. bigemina infection also induced a significant increase (p ⟨ 0.05) in hepatic malondialdehyde (MDA) and nitric oxide-derived products (NOx) concentra- tions as well as amount of endogenous hepatocytes DNA damage. Hepatic damage was also re- flected through the measurement of lactic acid dehydrogenase (LDH) and protein carbonyl con- tent (PCO) in liver cells. These two indices of liver injury were also significantly elevated (p ⟨ 0.5) during B. bigemina infection. Evaluation of correlation between assayed variables in infected rats revealed that MDA levels were positively correlated with PCO, NOx, LDH and DNA damage in the infected group and negatively correlated with GSH, CAT and TAC. There was also an inverse relationship between the antioxidant enzymes activities of GSH, CAT and TAC with PCO, NOx and DNA damage in infected rats. However, NOx showed positive correlation with PCO and DNA damage in infected rats. On the basis of the above results it can be concluded that the Ba- besia infection increases oxidative stress markers, protein carbonyl content and DNA damage and decreases antioxidant enzymes activities in the liver. These results suggest that B. bigemina infec- tion could alter the liver histopathology and causes DNA damage following oxidative stress in hepatic tissue. Further studies are needed to precisely define how hepatic tissue damage takes place in B. bigemina infection.

Protective Mechanisms of Quercetin on Cisplatin Induced Oxidative Damage in Hepatic Tissue of Wistar Rats

The present study was undertaken to investigate the cisplatin (cDDP) induced oxidative damage in hepatic tissue of wistar rats and mechanisms of protection by quercetin. A total of 24 wistar rats were randomly divided into four groups with six animals in each. Group I served as control, group II received cDDP (12 mg kg−1 body weight) and group III quercetin (50 mg kg−1 body weight) intra-peritoneally. Group IV received quercetin 6 h prior to cDDP administration intra-peritoneally. Administration of cDDP in rats resulted in significant (P < 0.05) elevation of plasma hepatic biomarkers, reduction of antioxidant system and marked histopathological alterations indicating acute hepatotoxicity. Treatment with quercetin prior to cDDP administration prevented hepatic dysfunctions as indicated by alterations in hepatic biomarkers, alleviated enzymatic and non-enzymatic components of the antioxidant system with reduced histopathological changes in hepatic tissue. The results suggest that cDDP induced hepatic damage is due to imbalance in oxidant and antioxidant system of hepatic tissue. The pretreatment with quercetin attenuated the oxidative damage induced by cDDP in hepatic tissue and this hepatoprotective effect of quercetin may be due to its direct scavenging of free radicals and/or enhancing antioxidant defense system of hepatic tissue in wistar rats.

Camellia sinensis L. Extract and Its Potential Beneficial Effects in Antioxidant, Anti-Inflammatory, Anti-Hepatotoxic, and Anti-Tyrosinase Activities.

The aims of this study were to investigate the potential benefits of antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase activities of a methanolic extract of fresh tea leaves (FTE) (Camellia sinensis L.). The antioxidant capacity was investigated using three different methods at different temperatures. The anti-inflammatory activity was studied in vitro by the inhibition of 5-lipoxygenase assay. The anti-hepatotoxic effect was investigated in CCl4-induced liver injury in rats. The anti-tyrosinase activities of the FTE and its principal phenolic compounds were investigated in l-3,4-dihydroxyphenylalanine (l-DOPA) oxidation by a mushroom tyrosinase. A molecular docking study was conducted to determine how the FTE’s principal catechins interact with the tyrosinase. The FTE exhibited the best shelf life at low temperatures and demonstrated concentration-dependent antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase effects compared to positive references. Treatment of rats with the FTE at 2000 mg/kg/day for 28 consecutive days reversed CCl4-induced oxidative damage in hepatic tissues by lowering the levels of alanine aminotransferase by 69% and malondialdehyde by 90%. Our findings suggest that the FTE has the capacity to scavenge free radicals and can protect against oxidative stress induced by CCl4 intoxication. The docking results were consistent with our in vitro data, indicating the anti-tyrosinase potency of the principal catechins.

Hepatoprotective Potential of Extracts from Seeds of Areca catechu and Nutgalls of Quercus infectoria

Aqueous extracts from seeds of Areca catechu L. (Arecaceae) (AC) and nutgalls of Quercus infectoria Oliv. (Fagaceae) (QI) were investigated for their hepatoprotective potential by studying their antioxidant capacity using four different methods, by determining their in vitro anti−inflammatory activity against 5-lipoxygenase, and by evaluating their hepatoprotective potential against liver injury induced by carbon tetrachloride (CCl4) in rats. AC and QI extracts exhibited potent antioxidant and anti-inflammatory activities. Treatment of rats with AC and QI extracts reversed oxidative damage in hepatic tissues induced by CCl4. It is suggested that extracts rich in either condensed or hydrolysable tannins and known for their potent antioxidant and anti-inflammatory activities, may potentially confer protection against oxidative stress−induced liver injury. These data should contribute to evidence-based traditional medicines for anti-inflammatory and hepatoprotective effects of both extracts.

Protective Effects of Amburoside A, a Phenol Glucoside from Amburana cearensis, against CCl4-Induced Hepatotoxicity in Rats

The aim of this study was to investigate the possible beneficial effects of amburoside A, AMB [4-(O-beta- D-glycopyranosyl)benzyl protocatechoate], against carbon tetrachloride (CCl (4)) toxicity in rats. AMB is a phenol glucoside from the Brazilian medicinal plant Amburana cearensis, popularly used for the treatment of respiratory tract affections. Acute AMB (25 and 50 mg/kg, I. P. or P. O.) treatments of CCl (4)-intoxicated rats significantly inhibited the increase in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as compared to the group treated with CCl (4) only. Histological studies showed less centrolobular necrosis and inflammatory cell infiltrates in the liver of animals treated with AMB plus CCl (4), when compared to the group treated with CCl (4) alone. In hepatic tissues, AMB at both doses inhibited CCl (4)-induced thiobarbituric acid-reactive substances (TBARS) formation, indicating a blockade of CCl (4)-induced lipid peroxidation. AMB also reversed the decrement in glutathione contents of hepatic tissues in CCl (4)-intoxicated rats. Furthermore, it restored catalase activity to normal values, which was significantly increased after CCl (4) treatment. Our results indicate that CCl (4)-induced oxidative damage in hepatic tissues is reversed by AMB treatment. The protective effect of AMB is probably due to the phenolic nature of this glucoside.

Protective effects of resveratrol against acetaminophen-induced toxicity in mice

This investigation elucidates the role of free radicals in acetaminophen (AA)-induced toxicity and the possible protection by resveratrol (RVT). BALB-c mice were injected with a single dose of 900mg/kg AA to induce toxicity, while RVT administred in a dose of 30mg/kg i.p. following AA. Mice were sacrificed 4h after AA injection to determine serum ALT, AST and tumor necrosis factor-alpha (TNF-alpha) levels in blood, and glutathione (GSH), malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and collagen contents in liver tissues. Formation of reactive oxygen species in hepatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probe. ALT, AST levels and TNF-alpha were increased significantly after AA treatment, and reduced with RVT. AA caused a significant decrease in GSH levels while MDA levels and MPO activity were increased in liver tissues. On the other hand when RVT administered following AA, depletion of GSH and accumulation of MDA and neutrophil infiltration were reversed back to control. Furthermore increased luminol and lucigenin CL levels in the AA group reduced by RVT treatment. Our results implicate that AA causes oxidative damage in hepatic tissues and RVT, by its potent antioxidant effects protects the liver tissue. These data suggest that RVT may be of therapeutic use in preventing hepatic oxidative injury due to AA toxicity.

Protective effects of ginkgo biloba against acetaminophen-induced toxicity in mice

The analgesic acetaminophen (AAP) causes a potentially fatal, hepatic centrilobular necrosis when taken in overdose. It was reported that these toxic effects of AAP are due to oxidative reactions that take place during its metabolism. In this study, we aimed to investigate the possible beneficial effect of Ginkgo biloba (EGb), an antioxidant agent, against AAP toxicity in mice. Balb/c mice were injected i.p. with: (1) vehicle, control (C) group; (2) a single dose of 50 mg/kg Ginkgo biloba extract, EGb group; (3) a single dose of 900 mg/kg i.p. acetaminophen, AAP group, and (4) EGb, in a dose of 50 mg/kg after AAP injection, AAP + EGb group. Serum ALT, AST, and tumor necrosis factor-alpha (TNF-alpha) levels in blood and glutathione (GSH), malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and collagen contents in liver tissues were measured. Formation of reactive oxygen species in hepatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lusigenin probe. Tissues were also examined microscopically. ALT, AST levels, and TNF-alpha were increased significantly (p < 0.001) after AAP treatment, and reduced with EGb. Acetaminophen caused a significant (p < 0.05-0.001) decrease in GSH levels while MDA levels and MPO activity were increased (p < 0.001) in liver tissues. These changes were reversed by EGb treatment. Furthermore, luminol and lusigenin CL levels in the AAP group increased dramatically compared to control and reduced by EGb treatment (p < 0.01). Our results implicate that AAP causes oxidative damage in hepatic tissues and Ginkgo biloba extract, by its antioxidant effects protects the tissues. Therefore, its therapeutic role as a "tissue injury-limiting agent" must be further elucidated in drug-induced oxidative damage.

Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis.

BackgroundThe exogenous administration of Insulin-like Growth Factor-I (IGF-I) induces hepatoprotective and antifibrogenic actions in experimental liver cirrhosis. To better understand the possible pathways behind the beneficial effect of IGF-I, the aim of this work was to investigate severe parameters involved in oxidative damage in hepatic tissue from cirrhotic animals treated with IGF-I (2 μg. 100 g-1. day-1). Iron and copper play an important role in oxidative mechanisms, producing the deleterious hydroxyl radical (*OH) that peroxides lipid membranes and damages DNA. Myeloperoxidase (MPO) and nitric oxide (NO) are known sources of free radicals and induce reduction of ferritin-Fe3+ into free Fe2+, contributing to oxidative damage.MethodsLiver cirrhosis was induced by CCl4 inhalation in Wistar male rats for 30 weeks. Healthy controls were studied in parallel (n = 10). Fe and Cu were assessed by atomic absoption spectrometry and iron content was also evaluated by Perls' staining. MPO was measured by ELISA and transferrin and ferritin by immunoturbidimetry. iNOS expression was studied by immuno-histochemistry.ResultsLiver cirrhosis was histologically proven and ascites was observed in all cirrhotic rats. Compared to controls untreated cirrhotic rats showed increased hepatic levels of iron, ferritin, transferrin (p < 0.01), copper, MPO and iNOS expression (p < 0.01). However, IGF-treatment induced a significant reduction of all these parameters (p < 0.05).Conclusionthe hepatoprotective and antifibrogenic effects of IGF-I in cirrhosis are associated with a diminution of the hepatic contents of several factors all of them involved in oxidative damage.