Dietary curcumin and capsaicin: Relationship with hepatic oxidative stress and apoptosis in rats fed a high fat diet.

BACKGROUND: Apoptosis plays a major role in fatty liver disease. High-fat diets are related to the onset of fatty liver disease and hepatic oxidant-antioxidant imbalance. Curcumin and capsaicin are somewhat beneficial in reducing hepatic triglycerides; this is most likely because they are known to downregulate reactive oxygen species (ROS) and apoptosis. OBJECTIVES: The aim of this study was to investigate the effects of curcumin and capsaicin on apoptosis through the oxidative effect in an animal model of fatty liver disease. MATERIAL AND METHODS: Male Sprague Dawley rats were fed a normal control diet, a high-fat diet (HFD; 60% of total calories from fat), a HFD+curcumin (1.5 g curcumin/kg HFD), a HFD+capsaicin (0.15 g capsaicin/kg HFD), or a HFD+curcumin+capsaicin (1.5 g curcumin and 0.15 g capsaicin/kg HFD). Liver lysate levels of BAX, Bcl-2 and caspase-3 were determined via immunoblotting. Caspase-3 activity was measured with a colorimetric caspase-3 measurement kit. Total antioxidant status (TAS) and total oxidant status (TOS) were assayed using commercial kits. The generation of hepatic ROS was measured with fluorimetry. Fragmentation of DNA was detected using the TUNEL method. RESULTS: High-fat diet caused increased expression of BAX and caspase-3, as well as increased TOS and caspase-3 activity, but decreased expression of Bcl-2. HFD+curcumin+capsaicin caused decreased BAX, caspase-3, TOS, and ROS levels as compared to HFD, but increased TAS and Bcl-2. A HFD +curcumin+capsaicin also decreased the number of TUNEL-positive cells. CONCLUSIONS: These results suggest that supplementation with curcumin and capsaicin balances the hepatic oxidant-antioxidant status and may have a protective role in the apoptotic process in an HFD-induced fatty liver model.

Effect of dietary curcumin and capsaicin on testicular and hepatic oxidant-antioxidant status in rats fed a high-fat diet.

This study investigated the effects of curcumin and capsaicin on testicular and hepatic oxidant-antioxidant status in rats fed a high-fat diet (HFD). Male Sprague-Dawley rats were divided into 5 groups (8 rats per group). The control group was fed a normal control diet (standard laboratory chow), the HFD group was fed HFD (60% of total calories from fat), the HFD+CUR group received HFD supplemented with curcumin (1.5 g curcumin/kg HFD), the HFD+CAP group was given HFD supplemented with capsaicin (0.15 g capsaicin/kg HFD), and the HFD+CUR+CAP group received HFD supplemented with curcumin and capsaicin for 16 weeks. Hepatic and testicular thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS), glutathione (GSH) levels, glutathione transferase activity, and Cu-Zn superoxide dismutase, glutathione peroxidase, and catalase protein expression and enzyme activities were measured. Protein expression was determined by Western blotting. GSH levels and antioxidant enzyme activities were measured with colorimetric methods. HFD slightly increased hepatic and testicular oxidative stress parameters. GSH levels did not change between groups. TBARS and ROS levels were significantly reduced in the HFD+CUR+CAP group compared with the HFD group. Liver and testis antioxidant enzyme activities and expression increased significantly with combined capsaicin and curcumin treatment. Curcumin and capsaicin treatment attenuated testicular and hepatic oxidative stress and enhanced the antioxidant defense system. The combination of capsaicin and curcumin with HFD seems to have some remarkable and beneficial effects on testicular oxidative damage in the fatty liver rat model.

High-fat diet plus carbon tetrachloride-induced liver fibrosis is alleviated by betaine treatment in rats.

Steatosis, the first lesion in non-alcoholic fatty liver disease (NAFLD), may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Steatosis predisposes the liver to oxidative stress, inflammation, and cytokines. Betaine (BET) has antioxidant, antiinflammatory and hepatoprotective effects. However, the effects of BET on liver fibrosis development are unknown. Rats were treated with high-fat diet (60% of total calories from fat) for 14weeks. Carbon tetrachloride (0.2mL/kg; two times per week; i.p.) was administered to rats in the last 6weeks with/without commercial food containing BET (2%; w/w). Serum liver function tests and tumor necrosis factor-α, insulin resistance, hepatic triglyceride (TG) and hydroxyproline (HYP) levels and oxidative stress parameters were determined along with histopathologic observations. Alpha-smooth muscle-actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and type I collagen (COL1A1) protein expressions and mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were evaluated. BET decreased TG and HYP levels, prooxidant status and fibrotic changes in the liver. α-SMA, COL1A1 and TGF-ß1 protein expressions, MMP-2, TIMP-1, and TIMP-2 mRNA expressions diminished due to BET treatment. BET has an antifibrotic effect and this effect may be related to its antioxidant and antiinflammatory actions together with suppression on HSC activation.

Betaine treatment decreased oxidative stress, inflammation, and stellate cell activation in rats with alcoholic liver fibrosis.

The aim of this study was to investigate the effect of betaine (BET) on alcoholic liver fibrosis in rats. Fibrosis was experimentally generated with ethanol plus carbon tetrachloride (ETH+CCl4) treatment. Rats were treated with ETH (5% v/v in drinking water) for 14 weeks. CCl4 was administered intraperitoneally (i.p.) 0.2mL/kg twice a week to rats in the last 6 weeks with/without commercial food containing BET (2% w/w). Serum hepatic damage markers, tumor necrosis factor-α, hepatic triglyceride (TG) and hydroxyproline (HYP) levels, and oxidative stress parameters were measured together with histopathologic observations. In addition, α-smooth muscle-actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and type I collagen (COL1A1) protein expressions were assayed immunohistochemically to evaluate stellate cell (HSC) activation. mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were also determined. BET treatment diminished TG and HYP levels; prooxidant status and fibrotic changes; α-SMA, COL1A1 and TGF-ß protein expressions; MMP-2, TIMP-1 and TIMP-2 mRNA expressions in the liver of fibrotic rats. In conclusion, these results indicate that the antifibrotic effect of BET may be related to its suppressive effects on oxidant and inflammatory processes together with HSC activation in alcoholic liver fibrosis.

Acute and long-term effects of hyperbaric oxygen therapy on hemorheological parameters in patients with various disorders.

Inhalation of 100% oxygen in a hyperbaric chamber has been accepted as a useful treatment for patients with various pathologies who suffer from hypoxia. The oxidative effects of hyperbaric oxygen (HBO) on RBCs have been investigated in animals but there is not enough data on hemorheological parameters in patients following HBO treatment (HBOT).In this study, we investigated the effect of HBO on hemorheological and haematological parameters during treatment. Red blood cell (RBC) deformability and aggregation, blood and plasma viscosity and superoxide dismutase activity were investigated in patients who underwent HBOT. Hematological parameters were determined by an electronic hematology analyzer. A Laser-assisted Optical Rotational Cell Analyzer (LORCA) was used to measure RBC deformability. RBC aggregation was measured for cells in autologous plasma and for cells resuspended in PBS containing Dextran70 (3% ) by using a Myrenne Aggregometer. A Wells-Brookfield cone/plate rotational viscometer was used for viscosity measurements. According to our results, a significant decrement of the hematocrit and the RBC count was observed after the 20th session of HBOT compared to the baseline, but none of the hemorheological parameters changed significantly. Our results showed that HBOT did not cause any significant changes in hemorheological parameters, thereby not representing any problems for the patients.

Blueberry treatment attenuated cirrhotic and preneoplastic lesions and oxidative stress in the liver of diethylnitrosamine-treated rats.

Diethylnitrosamine (DEN)-induced liver cancer normally develops in stages that progress from cirrhosis and carcinoma. Increased oxidative stress is suggested to play a role in DEN-induced carcinogenicity. Blueberries (BB) contain high antioxidant capacity. We investigated the effect of BB supplementation on development of DEN-induced cirrhosis and neoplastic lesions in the liver. Rats were injected with DEN (200 mg/kg; i.p.) three times with an interval of 15 days at 4, 6, and 8 weeks and sacrificed 8 weeks after the last DEN injection. They were also fed on 8% BB (w/w) containing chow for 16 weeks. Hepatic damage markers in serum were determined together with hepatic histopathological examinations. Hydroxyproline (HYP), malondialdehyde (MDA), diene conjugate (DC), protein carbonyl (PC), and glutathione (GSH) levels, and CuZn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and their mRNA expressions were measured. Protein and mRNA expressions of glutathione transferase-pi (GST-pi) were evaluated as a marker of preneoplastic lesions. BB supplementation decreased hepatic damage markers in serum and hepatic MDA, DC, and PC levels, but SOD, CAT, and GSH-Px activities and their mRNA expressions remained unchanged in DEN-treated rats. BB attenuated cirrhotic changes and decreased hepatic HYP levels and GST-pi expressions. Our results indicate that BB is effective in decreasing development of DEN-induced hepatic cirrhosis and preneoplastic lesions by acting as an antioxidant (radical scavenger) itself without affecting activities and mRNA expressions of antioxidant enzymes.

Effect of blueberry pretreatment on diethylnitrosamine-induced oxidative stress and liver injury in rats.

Diethylnitrosamine (DEN) treatment increases the generation of reactive oxygen species (ROS), apoptosis, necrosis and proliferation in the liver. Blueberries (BB; Vaccinium corymbosum L.) contain polyphenols and other active components and have high antioxidant capacities. We investigated the effect of BB pretreatment on DEN-induced liver injury and oxidative and nitrosative stress in male rats. Rats were fed with 5% and 10% BB containing diet for six weeks and DEN (200mg/kg; i.p.) was applied two days before the end of this period. Liver function tests were determined in serum and histopathological evaluation was performed in the liver tissue. Apoptosis-related proteins, Bax and B cell lymphoma-2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) expressions were also examined. Oxidative and nitrosative stress were evaluated in the liver by measuring thiobarbituric acid reactive substances, diene conjugate, protein carbonyl and nitrotyrosine levels, and glutathione levels and glutathione peroxidase, superoxide dismutase and glutathione transferase (GST) activities. Pretreatment with high dose of BB reduced apoptotic, necrotic and proliferative changes in the liver induced by DEN. Dietary BB also decreased hepatic lipid peroxidation, protein oxidation and nitrotyrosine levels together with increased GST activity. In conclusion, BB may have an inhibiting effect on acute liver injury by reducing apoptosis, necrosis, proliferation, oxidative and nitrosative stress in DEN-treated rats.

The effect of chronic diazepam administration on lipid peroxidation and Ca2+ -ATPase activity in rat liver.

Chronic administration of diazepam (DZP) caused an increase in malondialdehyde (MDA) levels and a decrease in glutathione (GSH) content. DZP also markedly lowered Ca2+ATPase activity. Treatment with Se plus vitamin E reduced MDA levels and increased GSH content. Our results suggest that, increased lipid peroxidation together with alteration in Ca2+ -ATPase activity may play a role in DZP induced hepatic injury and Se plus vitamin E treatment may contribute to the attenuation of DZP induced hepatotoxicity.

Cholesterol plus methionine feeding do not induce lipid peroxidation and atherosclerotic changes in the rat aorta.

The purpose of this study was to investigate whether cholesterol plus methionine feeding may be a convenient model to produce atherosclerosis in rats, and also to examine the contribution of oxidative stress to this development. For this reason, lipid peroxide levels and antioxidant enzyme activities in the liver and aorta as well as histopathological findings were determined in male Wistar-albino rats fed a diet supplemented with cholesterol plus cholic acid and methionine for six months. This diet was found to increase lipid peroxide levels in the liver of rats. Hepatic glutathione peroxidase (GSH-Px) and catalase (CAT) activities increased, but superoxide dismutase (SOD) activity remained unchanged. In conclusion, cholesterol and methionine feeding in rats did not cause oxidative stress and atherosclerotic changes in the aorta, although hepatic prooxidant-antioxidant balance was affected by this diet.