育阴软肝颗粒剂对肝纤维化大鼠TGF-β1表达的影响

目的：观测育阴软肝颗粒剂对大鼠肝纤维化模型的防治作用及对转化生长因子-β1（TGF-β1）表达的影响。方法：将Wistar大鼠分为6组（n=10）,注射四氯化碳、饲以高脂饲料并饮用20%乙醇6周复制肝纤维化大鼠模型,经6.2~24.8 g/kg育阴软肝颗粒剂干预（qd）6周后,测定肝纤维化大鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）活性、透明质酸（HA）、Ⅲ型前胶原（PCⅢ）、Ⅳ型胶原（C-Ⅳ）及板层素（LN）含量,观测肝组织病理学及肝组织TGF-β1表达的变化,对育阴软肝颗粒剂防治肝纤维作用及机制进行研究。结果：实验第7周,模型组大鼠肝组织出现明显的纤维化病变（P<0.01）;与模型组比较,6.2~24.8g/kg的育阴软肝颗粒剂能明显降低肝指数以及血清ALT、AST活性与HA、PCⅢ、C-Ⅳ、LN含量,缓解肝组织纤维化病理变化,抑制纤维化肝组织TGF-β1的表达（P<0.05,0.01）。结论：育阴软肝颗粒剂对多因素复制肝纤维化大鼠造模具有明显的治疗作用,而抑制TGF-β1的表达可能是其作用机制之一。     

Blueberry extract attenuates γ-radiation-induced hepatocyte damage by modulating oxidative stress and suppressing NF-κB in male rats

Radiation exposure is known to produce many harmful effects in biological systems, and these effects are often mediated by oxygen free radicals. Because blueberries are rich in antioxidant compounds such as anthocyanins and phenolic acids, we divided forty adult rats into four treatment groups of 10 (G1–4) as follows: G1 rats were used as a control, G2 rats were irradiated with 8?Gy at 2?Gy/week at a dose rate of 0.5?Gy/min, G3 rats were administered blueberry extract (200?mg/kg) and G4 rats were administered blueberry extract during the same irradiation period. In subsequent determinations, γ-irradiated rats had increased levels of cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL), and significantly elevated liver enzyme activities, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), and total bilirubin. In contrast, significant reductions in albumin, total protein and globulin were observed, whereas gamma irradiation decreased activities of the antioxidant enzymes glutathione (GSH), catalase (CAT), xanthine dehydrogenase (XDH) and superoxide dismutase (SOD). We also observed incremental increases in DNA fragmentation percentages and histopathological changes in liver tissues. Serum pro-inflammatory cytokine levels (IL-6, IL-10 and TNF-α) were significantly elevated and hepatic NF-кB was upregulated. In G4 rats, treatments with blueberry extract restored liver pro-oxidant status, reduced cytokine levels, ameliorated histopathological parameters and reduced DNA damage. In conclusion, γ-radiation exerts toxic effects in the rat livers, and blueberry extract is protective against these.     

Effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption

This study examined the effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption. At the beginning of experiment (week 0), according to both the plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, rats (n = 24) were divided into 3 groups and fed with a standard diet (group C), a diet containing ethanol (group E), or a diet containing ethanol and β‐carotene (group E+B). After 10 weeks, plasma AST and ALT, fat accumulation in the liver, antioxidant enzyme activities in erythrocytes and the liver, malondialdehyde (MDA), and α‐tocopherol and retinol in plasma and hepatic samples were analyzed. The chronic alcohol diet significantly increased AST and ALT levels in plasma, and these changes were prevented by supplementing the diet with β‐carotene. Glutathione (GSH) in erythrocytes and in the liver was significantly elevated in rats fed with a diet containing β‐carotene. The results indicate that β‐carotene supplementation can prevent ethanol‐induced liver damage and increase GSH concentrations in erythrocytes and the liver. Copyright © 2009 John Wiley & Sons, Ltd.     

Tangeretin ameliorates bisphenol induced hepatocyte injury by inhibiting inflammation and oxidative stress

Bisphenol A (BPA) is an industrial toxicant that can potentially damage the liver. Tangeretin (TGN) is a natural flavonoid that displays various pharmacological activities. This experiment was carried out to evaluate the protective effects of TGN against BPA-induced hepatic impairment in the male albino rat. Twenty-four male albino rats were equally divided into four different groups: control, BPA (100 mg/kg), BPA + TGN (100 mg/kg + 50 mg/kg) and TGN (50 mg/kg). BPA exposure significantly decreased the activities of catalase (CAT), superoxidase dismutase (SOD), peroxidase (POD), glutathione reductase (GSR), glutathione S-transferase (GST), and glutathione (GSH) content while substantially increasing the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H₂O₂) levels. A substantial increase in the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) was also observed in BPA treated rats. Moreover, BPA significantly increased the inflammatory markers, including tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB), Interleukin-6 (IL-6), Interleukin-1β (IL-1β)levels, cyclooxygenase-2 (COX-2) activity, and histopathological damages. However, co-treatment with TGN efficiently minimized the BPA-induced biochemical, inflammatory, and histopathological impairments in rat liver. The present study shows that TNG has significant potential to avert BPA-induced liver damage to its antioxidant and anti-inflammatory properties.     

Protective effect of pinitol against D-galactosamine-induced hepatotoxicity in rats fed on a high-fat diet

The protective effect of pinitol against D-galactosamine (GalN)-induced liver damage was examined. Forty male Sprague-Dawley rats were divided into normal control, GalN control, and pinitol groups (0.5%, 1%, and 2%). After 8 weeks of feeding, a single dose of GalN (650 mg/kg) was administered 24 h before their sacrifice. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and tumor necrosis factor-alpha (TNF-alpha) levels were significantly increased after an injection with GalN (P<0.05), but pinitol supplementation at the level of 0.5% reversed these changes to normal levels. Significant decreases in serum triglyceride and cholesterol and increases in hepatic cholesterol were observed in GalN-intoxicated rats. However, supplementation with pinitol significantly attenuated these trends. In addition, pinitol elevated the Mn-superoxide dismutase, glutathione reductase, and catalase activities, prevented hepatic lipid peroxidation, and restored the hepatic GSH levels and cytochrome P450 2E1 function. Thus, 0.5% pinitol supplementation protected the rats from the hepatotoxicity induced by GalN, at least part of its effect being attributable to attenuation of the oxidative stress and inflammatory process promoted by GalN.     

Characterization of the protective effects of melatonin and related indoles against alpha-naphthylisothiocyanate-induced liver injury in rats

The protective effect of melatonin, 6-hydroxymelatonin and N-acetylserotonin against alpha-naphthylisothiocyanate (ANIT)-induced liver injury was investigated and compared in rats injected once with the hepatotoxicant (75 mg/kg body weight). In rats injected with ANIT alone, liver injury with cholestasis developed within 24 h, as indicated by both serum levels of alanine aminotransferase (SGPT) and aspartic acid aminotransferase (SGOT) activities and serum total bilirubin concentration. The administration of melatonin or 6-hydroxymelatonin (10 mg/kg body weight) to ANIT-injected rats reduced significantly the serum levels of both SGPT and SGOT and the serum total bilirubin concentration. For all hepatic biochemical markers, melatonin was more effective that 6-hydroxymelatonin. By comparison, the administration of N-acetylserotonin (10 mg/kg body weight) to ANIT-injected rats did not reduce the serum levels of either hepatic enzymes or the serum total bilirubin concentration. In ANIT-injected rats, hepatic lipid peroxidation (LPO) was significantly higher than in control animals and this increase was significantly reduced by either melatonin, 6-hydroxymelatonin or N-acetylserotonin. Furthermore, ANIT treatment caused a significant reduction in liver microsomal membrane fluidity and this reduction was completely reversed by the three indoles. The liver from ANIT-injected rats showed several histopathological alterations; above all there was an acute infiltration of polymorphonuclear neutrophils and an increase in the number of apparent apoptotic hepatocytes. The concurrent administration of melatonin reduced the severity of all morphological alterations, specially the neutrophil infiltration and the number of presumed apoptotic cells. On the contrary, the administration of 6-hydroxymelatonin or N-acetylserotonin did not provide any protective effect in terms of the histopathological alterations. These results indicate that melatonin protects against ANIT-induced liver injury with cholestasis in rats, and suggests that this protective effect is likely due to its antioxidant properties and above all to its capacity to inhibit liver neutrophil infiltration, a critical factor in the pathogenesis of ANIT-induced liver injury. 6-hydroxymelatonin, although able to provide partial protection against the ANIT-induced hepatic injury, probably through its antioxidant properties by mechanisms that are unclear, was unable to reduce neutrophil infiltration. Finally, N-acetylserotonin in the experimental conditions of this study, only exhibited some antioxidant protection but had no protective effect against ANIT-induced hepatic damage.     

Resveratrol attenuates hyperglycemia-mediated oxidative stress,proinflammatory cytokines and protects hepatocytes ultrastructure in streptozotocin–nicotinamide-induced experimental diabetic rats

The present study was hypothesized to investigate the hepatoprotective nature of resveratrol in averting hyperglycemia-mediated oxidative stress by measuring extent of oxidant stress and levels of proinflammatory cytokines and antioxidant competence in the hepatic tissues of streptozotocin–nicotinamide-induced diabetic rats. After the experimental period of 30 days, the pathophysiological markers such as serum bilirubin and hepatic aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were studied in addition to hepatic TNF-α, IL-1β, IL-6, NF-κB p65 and nitric oxide (NO) levels in control and experimental groups of rats. The levels of vitamin C, vitamin E and reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) were determined in the liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides, hydroperoxides and protein carbonyls. A portion of liver was processed for histological and ultrastructural studies. Oral administration of resveratrol (5 mg/kg b.w.) to diabetic rats showed a significant decline in hepatic proinflammatory cytokines and notable attenuation in hepatic lipid peroxides, hydroperoxides and protein carbonyls. The diminished activities of hepatic enzymic antioxidants as well as the decreased levels of hepatic non-enzymic antioxidants of diabetic rats were reverted to near normalcy by resveratrol administration. Moreover, the histological and ultrastructural observations evidenced that resveratrol effectively rescues the hepatocytes from hyperglycemia-mediated oxidative damage without affecting its cellular function and structural integrity. The findings of the present investigation demonstrated the hepatocyte protective nature of resveratrol by attenuating markers of hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic tissues of diabetic rats.     

Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats

Free radicals and oxidative stress have been implicated in the etiology of diabetes and its complications. This in vivo study has examined whether subacute administration of pycnogenol, a French pine bark extract containing procyanidins that have strong antioxidant potential, alters biomarkers of oxidative stress in normal and diabetic rats. Diabetes was induced in female Sprague-Dawley rats by a single injection of streptozotocin (90 mg/kg body weight, ip), resulting (after 30 days) in subnormal body weight, increased serum glucose concentrations, and an increase in liver weight, liver/body weight ratios, total and glycated hemoglobin, and serum aspartate aminotransferase activity. Normal and diabetic rats were treated with pycnogenol (10 mg/kg body weight/day, ip) for 14 days. Pycnogenol treatment significantly reduced blood glucose concentrations in diabetic rats. Biochemical markers for oxidative stress were assessed in the liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was restored to normal levels after pycnogenol treatment. Additionally, diabetic rats treated with pycnogenol had significantly elevated levels of reduced glutathione and glutathione redox enzyme activities. The results demonstrate that pycnogenol alters intracellular antioxidant defense mechanisms in streptozotocin-induced diabetic rats.     

Carnosine and taurine treatments decreased oxidative stress and tissue damage induced by d-galactose in rat liver

d-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat chow) for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-0050x), and glutathione transferase (GST) activities were determined. Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated. Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL-treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also diminished. CAR or TAU treatments caused significant decreases in serum ALT and AST activities. These treatments decreased apoptosis and increased proliferation and ameliorated histopathological findings in the livers of GAL-treated rats. Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH-Px (non significant in TAU?+?GAL group) activities. These treatments did not alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate that CAR and TAU restored liver prooxidant status together with histopathological amelioration in GAL-induced liver damage.     

Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats

BACKGROUND: Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines. OBJECTIVE: The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL). METHODS: Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-alpha, IL-1beta and IL-6 were also assayed in plasma samples. RESULTS: In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p<0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p<0.05-p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment. CONCLUSION: Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.     

Efficacy of Dietary Lipid Control in Healing High-Fat and High-Cholesterol Diet-Induced Fibrotic Steatohepatitis in Rats

Nonalcoholic steatohepatitis is related to lifestyle, particularly to dietary habits. We developed diet-induced fibrotic steatohepatitis model stroke-prone spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rats showing steatosis, hepatic inflammation, and severe fibrosis induced by high-fat and -cholesterol (HFC) diet feeding. We aimed to clarify the efficacy of dietary intervention on the disease before and after the appearance of fibrosis. Male SHRSP5/Dmcr rats were divided into 9 groups; of these, 6 groups were fed control or HFC diet for several weeks and the remaining 3 groups represented the dietary intervention groups, which were fed the control diet after HFC diet feeding for 2 (before the appearance of fibrosis) or 8 (after the appearance of fibrosis) weeks. Dietary intervention before the appearance of fibrosis significantly improved the steatosis and reset the increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum total cholesterol (TC) levels. However, dietary intervention after the appearance of fibrosis was unable to reset the levels of hepatic TC, serum ALT, and fibrogenesis-related markers and had only a minor influence on hepatic fibrosis, although it reset the increased expression of transforming growth factor (TGF)-β1 and α-smooth muscle actin (SMA). It was noted that dietary intervention improved the increased AST levels; however, aggregated CD68-positive cells were still observed around the fibrosis area, which may be related to the findings of inflammatory cytokine mRNAs. Taken together, dietary intervention for fibrotic steatohepatitis improved steatosis, although it could not completely improve fibrosis.     

MnSOD expression inhibited by electromagnetic pulse radiation in the rat testis

Male Sprague Dawley rats were exposed to EMP irradiation of 100?kV/m peak-to-peak e-field intensity and different numbers of pulses. Rat sperm samples were prepared for analysis of sperm qualities; Testes were assessed by transmission electron microscopy and serum hormone concentrations were examined by radioimmunoassay; Enzymatic activities of Total-superoxide dismutase(T-SOD) and manganese-superoxide dismutase (MnSOD), the mRNA levels of MnSOD and cuprozinc-superoxide dismutase (CuZnSOD), and the density of malondialdehyde (MDA) were also determined. EMP irradiation did not affect spermatozoon morphology, micronucleus formation rate, sperm number or viability, but the acrosin reaction rate decreased at 24?h and 48?h and recovered by 72?h after irradiation as compared to the controls. The ultrastructure of rat testis displayed more serious damage at 24?h than at other time points (6?h, 12?h, 48?h). Serum levels of luteotrophic hormone (LH) and testosterone (T) were elevated in irradiated rats as compared to controls. After irradiation, enzymatic activities of T-SOD and MnSOD were reduced by 24?h, consistent with the changes observed in MnSOD mRNA expression; MDA content increased at 6?h in turn. These studies have quantified the morphological damage and dysfunction in the rat reproductive system induced by EMP. The mechanism of EMP induced damage may be associated with the inhibition of MnSOD expression.     

Effect of surgically induced cholestasis on the levels of hepatic zinc and metallothionein in rat liver

Early effects of experimental cholestasis on the homeostasis of zinc (Zn) and metallothionein (MT) were studied in rats which had undergone bile duct ligation for 0, 3, 6, 9, 12, 16, 20, and 24 h. Transient increases in hepatic Zn levels were observed at 9 h but returned to control values at 12 h. Serum Zn levels increased at 24 h. Cholestasis was confirmed by increased serum alkaline phosphatase (AP) activity. MT increased at 3 h and reached a maximum level at 12 h and remained elevated even at 24 h after the onset of experimental cholestasis. No hepatocellular damage was detected according to the results of alanine aminotransferase (ALT) activities in serum. These results shown that the increases in Zn observed in liver are related to bile stagnation rather than to a hepatocellular damage and that increased MT occurs concurrently with increased hepatic Zn. These observations suggest that the cellular levels of Zn in cholestasis is regulated by homeostatic mechanisms, of which one could be mediated by MT.     

Arsenic trioxide,a cancer chemo drug hampers fibrotic liver regeneration by interrupting oxidative stress rekindling and stellate cell rejuvenation

After withdrawal of liver toxic insult, the spontaneous regenerative potential of the liver is well reported in the literature. On the other hand, various molecules have been reported to promote as well as delay such natural regeneration. This current study investigates the involvement of arsenic trioxide (ATO) medication at chemotherapeutic dose on the spontaneous regeneration of the CCl₄ induced fibrotic liver. Liver injury markers, such as albumin and SGOT, SGPT, and ALP activities, in serum indicated that ATO supplementation during liver regeneration hampers the rejuvenation process. The hepatic architecture as well as the degree of fibrosis by hematoxylin and eosin and Sirius red staining confirms the above findings. The reduced hepatic antioxidant system and elevated oxidative stress markers, such as lipid peroxidation and 8-hydroxy deoxy-guanosine-positive hepatocytes in ATO supplied rats, display the persistence of oxidative stress when compared with healthy controls and the normal regeneration model. Immuno-histochemical localization of Ki-67 indicates that mitotically active hepatocytes were fewer in the ATO given rats when compared with normal regeneration rats. Further delay in hepatic fibrinolysis was monitored by matrix metalloproteinase zymography assay in the ATO-given animals. Poly(ADP-ribose) polymerase 1 expression demonstrates elevated hepatocyte apoptosis with ATO. Furthermore, increased α-smooth muscle actin indicates that the stellate cells are in an activated state in ATO supplemented fibrotic animals. In conclusion, it's observed that ATO supplementation to the fibrotic liver delays oxidative stress revitalization and maintains stellate cells in the active form, thereby delaying liver regeneration, and the health status of the liver must be taken into account before administering drugs like ATO.     

Diallyl sulfide ameliorates carbon tetrachloride‐induced hepatotoxicity in rats via suppressing stress‐activated MAPK signaling pathways

The underlined effects of diallyl sulfide (DAS) against CCL₄‐induced oxidative, inflammatory, and apoptotic acute hepatic damage were assessed. Administration of DAS (50, 100, and 200 mg/kg) along with CCL ₄ effectively mitigated serum aspartate aminotransferase, alanine aminotransferase activities, MDA, TNF‐α, IL‐1β, and MCP‐1 levels, as well as significantly restored HO‐1, GSH levels and SOD activity in liver tissues compared with those in rats treated with CCL ₄. Moreover, DAS inhibited CCL ₄‐induced increase of liver NF‐κB (p65), Bax, p38 MAPK, and JNK protein expression. In addition, DAS accelerated protein expression of Nrf2 and Bcl‐2. The hepatoprotective properties of DAS were further confirmed by the reduced severity of hepatic damage as demonstrated by histopathological findings. In conclusion, DAS achieved its protective potential against CCL4‐induced hepatotoxicity through antiapoptotic activity, as well as the synchronized modulation of NF‐κB and Nrf2 for the favor of antioxidant/anti‐inflammatory effects via suppression of the upstream stress‐activated MAPKs pathways.     

Serum IGF-1 levels correlate negatively to liver damage in diabetic rats

Abstract

Diabetes and insulin resistance frequently cause liver damage. Diabetes also causes reduction in liver and blood IGF-1 levels. We investigated the relation between liver damage and IGF-1 levels in diabetic rats. Fourteen Wistar albino rats were divided into control and diabetic groups. Diabetes was induced by streptozotocin. Rats were sacrificed for biochemical and histologic examinations 2 weeks after streptozotocin injection. Serum and liver IGF-1 levels were decreased, liver malondialdehyde (MDA) levels were increased, glutathione peroxidase (GPx) enzymes activities were decreased and serum alanine aminotransferase (ALT) levels were increased in diabetic group. Microscopic examination of liver revealed that normal tissue organization was disrupted in streptozotocin-induced diabetic rats. There was a strongly positive correlation between blood glucose levels and liver injury, and blood and liver IGF-1 levels. There was a strongly negative correlation between blood IGF-1 levels and hepatic injury. Our results suggest that reduction of blood IGF-1 levels correlates with hepatic injury and circulating IGF-1 levels may have predictive value for determining hepatic damage that results from diabetes. In addition, circulating IGF-1 levels are correlated with glutathione levels and the oxidative stress status of diabetic rat liver.     

Effect of a polyherbal formulation, Ambrex, on butylated hydroxy toluene (BHT) induced toxicity in rats

Effect of polyherbal formulation Ambrex was evaluated in butylated hydroxytoluene (BHT) induced toxicity of lungs and liver in rats. Toxicity was produced by administering BHT (500 mg/kg/day) for 3 days. Lung damage was evidenced by elevated levels of broncho alveolar lavage fluid (BAL) parameters such as protein, lactate, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and glucose-6-phosphate dehydrogenase (G6PDH). Liver damage was proved by elevated levels of serum protein and markers such as LDH, ALP, aspartate amino transferase (AST), alanine amino transferase (ALT), decreased level of lipid peroxides (LPO) in serum and glutathione (GSH) in liver. Administration of aqueous suspension of Ambrex (50 mg/kg orally) retained these elevated levels of BAL-protein, lactate, LDH, ALP, ACP, G6PDH and serum-protein, LDH, ALP, AST and ALT at near normal values. Decreased level of liver GSH was retained at near normalcy in Ambrex pretreated BHT-administered animals. There was no change in liver LPO in all the four groups.     

Preventive effect of omega-3 fatty acids in a rat model of stress-induced liver injury

Omega-3 fatty acids are gaining attention as a therapeutic agent of many diseases. Their protective effect in a variety of diseases has been demonstrated. To the best of our knowledge, this is the first study on omega-3 fatty acids related to acute cold-restraint stress (CRS) induced hepatic dysfunction in rats. Forty adult male Sprague–Dawley albino rats were used and classified into: control, omega-3 group, each rat was pretreated with omega-3 fatty acids; CRS group, rats were subjected to acute CRS for 6 hr; and CRS group pretreated with omega-3 fatty acids. Serum was obtained to determine corticosterone (CORT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-α (TNF-α) levels. Hepatic malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured. Also, liver tissues were taken for histological examination and immunohistochemical assessment of the apoptotic marker, caspase-3. Results showed that pretreatment of stressed rats with omega-3 fatty acids led to significant decrease in hepatic MDA and increase in TAC levels. They reduced serum levels of CORT, ALT, AST, and TNF-α. Also, they improved liver damage and suppressed hepatic caspase-3 expression. In conclusion, pretreatment of stressed rats with omega-3 fatty acids has ameliorated stress-induced liver damage due to their antioxidant, anti-inflammatory, and antiapoptotic effects. So, they can be used to minimize stress complications on the liver.