Hamadi Fetoui

Hypolipidemic and hepatoprotective effects of flax and pumpkin seed mixture rich in ω-3 and ω-6 fatty acids in hypercholesterolemic rats

Flax and pumpkin seeds are a rich source of unsaturated fatty acids, antioxidants and fibers, known to have anti-atherogenic and hepatoprotective activities. These effects were evaluated in Wistar rats fed with 1% cholesterol diet. The study was performed on 30 male rats divided into three groups: a control group (CD), CD-chol group fed diet with 1% cholesterol and MS-chol group fed diet enriched with flax and pumpkin seed mixture. In CD-chol group, total cholesterol TC, triacylglycerol TG in plasma and liver, plasma LDL-C, atherogenic index AI and LDL/HDL ratio significantly increased. In MS-chol group lipid parameters decreased significantly, plasma and liver fatty acid composition showed an increase of PUFAs (ALA and LA), and MUFAs (oleic and eicosaenoic acid) and a decrease of SFA (palmitic and stearic acid). In plasma and liver of MS-chol group, malondialdehyde levels decreased and the efficiency of antioxidant defense system was improved compared to CD-chol group. Liver histological sections showed lipid storage in hepatocytes of CD-chol group and an improvement was noted in MS-chol group. Our results suggested that flax and pumpkin seed mixture had anti-atherogenic and hepatoprotective effects which were probably mediated by unsaturated fatty acids present in seed mixture.

Toxic effects of lambda-cyhalothrin, a synthetic pyrethroid pesticide, on the rat kidney: Involvement of oxidative stress and protective role of ascorbic acid.

Lambda-cyhalothrin is a synthetic pyrethroid insecticide used worldwide in agriculture, home pest control, protection of foodstuff and disease vector control. The objective of this study was to investigate the propensity of lambda-cyhalothrin (LTC) to induce oxidative stress, changes in biochemical parameters and enzyme activities in the kidney of male rats and its possible attenuation by Vitamin C (vit C). Renal function, histopathology, tissue malondialdehyde (MDA), protein carbonyl (PCO) levels, antioxidant enzyme activities and reduced glutathione (GSH) levels were evaluated. Exposure of rats to lambda-cyhalothrin, during 3 weeks, caused a significant increase in kidney MDA and protein carbonyl levels (p<0.01) as compared to controls. Co-administration of vitamin C was effective in reducing MDA and PCO levels. The kidney of LTC-treated rats exhibited severe vacuolations, cells infiltration and widened tubular lumen. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were significantly decreased due to lambda-cyhalothrin exposure. Co-administration of vitamin C ameliorated the increase in enzymatic activities of aminotransferases (AST and ALT), lactate dehydrogenase (LDH), creatinine and urea levels and improved the antioxidant status. These data indicated the protective role of ascorbic acid against lambda-cyhalothrin-induced nephrotoxicity and suggested a significant contribution of its antioxidant property to these beneficial effects.

Oxidative stress induced by lambda-cyhalothrin (LTC) in rat erythrocytes and brain: Attenuation by vitamin C.

The objective of this study was to investigate the propensity of lambda-cyhalothrin (LTC) to induce oxidative stress in blood and brain of male Wistar rats and its possible attenuation by vitamin C. Rats were randomly divided into four groups: group I served as control rats. group II was treated daily with 200mgvit C/(kgbw) administered by intraperitoneal way. Rats of group III have received orally 668ppm LTC. Animals of group IV were treated with LTC and vitamin C. A decrease of some hematologic parameters (RBC, Hb, Ht: p<0.01) and a significant increase of MDA levels (p<0.05) in erythrocytes and brain were observed in LTC group compared to controls. Antioxidant enzyme activities in both tissues were modified in LTC group compared to controls. Administration of vitamin C ameliorated these parameters. Our results indicated the potential effects of LTC to induce oxidative damage in tissues and the ability of vitamin C to attenuate LTC-induced oxidative damage.

Lambda-cyhalothrin-induced biochemical and histopathological changes in the liver of rats: ameliorative effect of ascorbic acid.

Pyrethroid pesticides were used preferably over organochlorines and organophosphates due to their high effectiveness, low toxicity to non-target organisms and easy biodegrability. It has widespread applications in agriculture through the world and in Tunisia. The present study investigates lambda-cyhalothrin (LTC) effects on biochemical parameters, hepatotoxicity and their attenuation by vitamin C. Male Wistar rats were randomly divided into three groups of seven each: a control group (C) and two treated groups during 3 weeks with LTC administrated either alone in drinking water for LTC group or coadministred with vitamin C for LTC+vit C group. Lactate deshydrogenase (LDH) activity was significantly increased in liver (+51%, p<0.001) and in plasma (+40%, p<0.001) compared to those of control group. A significant increase of malondialdehyde (MDA) levels in liver (+53%; p<0.001) associated with a decrease in antioxidants enzyme activities and reduced glutathione (GSH) content was observed in LTC group compared to controls. The administration of vitamin C to LTC+vit C group improved all parameters studied. We conclude that LTC induces oxidative stress and modifies biochemical parameters and histological aspects of liver. Administration of vitamin C alleviates the toxicity induced by this synthetic pyrethroid insecticide.

Evaluation of the antioxidant, anti-inflammatory and hepatoprotective properties of vanillin in carbon tetrachloride-treated rats.

The antioxidant and anti-inflammatory effects of vanillin are considered as important forces in the protection against liver injury and fibrosis. This study investigated the protective effects of vanillin against carbon tetrachoride (CCl(4))-induced hepatotoxicity in rat. Pretreatment with vanillin prior the administration of CCl(4) significantly prevented the decrease of protein synthesis and the increase in plasma alanine (ALT) and aspartate (AST) aminotransferases. Furthermore, it inhibited hepatic lipid peroxidation (MDA) and protein carbonyl (PCO) formation and attenuated the (CCl(4))-mediated depletion of antioxidant enzyme catalase and superoxide dismutase (SOD) activities and glutathione level (GSH) in the liver. In addition, vanillin markedly attenuated the expression levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) and prevented CCl(4)-induced hepatic cell alteration and necrosis, as indicated by liver histopathology. These findings suggest that the antioxidant and anti-inflammatory effects of vanillin against CCl(4)-induced acute liver injury may involve its ability to block CCl(4)-generated free radicals.

Mitigating effects of antioxidant properties of Artemisia campestris leaf extract on hyperlipidemia, advanced glycation end products and oxidative stress in alloxan-induced diabetic rats

Artemisia campestris is used as antivenom and anti-inflammatory Tunisian folk medicine. Recently, increased oxidative stress was shown to play an important role in the etiology and pathogenesis of diabetes mellitus and its complications. This study was designed to examine the effects of A. campestris leaf aqueous extract (Ac) on alloxan-induced diabetic rats by measuring glycemia, lipid profile, lipid peroxidation (MDA), protein carbonyl content (PCO), advanced oxidation protein products (AOPP), activities of both non-enzymatic and enzymatic antioxidants. Results of our study showed an increase in blood glucose levels, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), a decrease in high-density lipoprotein cholesterol (HDL-c) level and disturbed antioxidant enzyme activities (CAT, SOD, GPx) in the pancreatic tissue of diabetic rats. Furthermore, MDA, PCO and AOPP were elevated in the pancreas of the diabetic rats. The administration of Ac to diabetic rats at a dose of 200mgkg(-1)bw resulted in a significant reduction in glycemia, TC, TG, LDL-c, pancreas LPO, PCO and AOPP levels, CAT and GPx activities associated with an elevation of GSH content and SOD activity in comparison with diabetic group. We conclude that A. campestris aqueous extract may be effective for correcting hyperglycemia and preventing diabetic complications.

Antidiabetic effect of flax and pumpkin seed mixture powder: effect on hyperlipidemia and antioxidant status in alloxan diabetic rats

Reactive oxygen species play a crucial role in the pathogenesis of diabetes and its complications. This study aims to examine the effects of flax and pumpkin powder seed mixture on alloxan induced diabetes in Wistar rats. Animals were allocated into three groups of six rats each: a control group (CD), diabetic group (DD) and diabetic rats fed with flax and pumpkin seed mixture (DMS) group. The diabetic rats (DD) presented a significant increase in glycemia, plasma and liver lipid parameters such as total lipid, total cholesterol and triglycerides compared to the control group (CD). In addition, plasma and liver malonaldialdehyde levels (MDA, an index of lipid peroxidation) significantly increased compared to (CD). Antioxidant enzymes activities such as catalase, superoxide dismutase, and reduced glutathione (GSH) levels significantly decreased in the plasma and liver of diabetic rats compared to controls. Diet supplemented with flax and pumpkin seed mixture in the DMS group ameliorated antioxidant enzymes activities and level of GSH in diabetic rats and significantly decreased MDA levels. The present study revealed a significant increase in the activities of aspartate aminotransferase and alanine aminotransferase on diabetic status, indicating considerable hepatocellular injury. The administration of flax and pumpkin seed mixture attenuated the increased levels of the plasma enzymes produced by the induction of diabetes and caused a subsequent recovery towards normalization comparable to the control group animals. Our results thus suggest that flax and pumpkin seed mixture supplemented to diet may be helpful in preventing diabetic complications in adult rats.

Naringenin reduces cholesterol-induced hepatic inflammation in rats by modulating matrix metalloproteinases-2, 9 via inhibition of nuclear factor κB pathway.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of hepatic abnormalities that extends from isolated steatosis to non-alcoholic steatohepatitis (NASH) and steatofibrosis. NASH is the progressive form of the disease that can lead to fibrosis, cirrhosis and hepatocellular carcinoma. Naringenin (NGEN), a healthful food, increases resistance to oxidative stress, inflammation and protects against multiple organ injury in various animal models. However, specific mechanisms responsible for such effects are poorly understood. Thus, this study investigates the effect of treatment with NGEN (50mg/kg) on oxidative events and the molecular mechanisms underlying inflammatory changes triggered in the rat liver by a high cholesterol diet for 90 days. NGEN significantly decreased the plasma fatty acid composition, the hepatic pro-inflammatory mediators and the expression of relevant genes including tumor necrosis factor-α, interlukin-6, interleukin-1β, inducible nitric oxide synthase and matrix metalloproteinases (MMP-2, 9), EGF-like module-containing mucin-like hormone receptor-like 1 (macrophage F4/80-specific gene); which suggests a reduced macrophage infiltration, and inhibited oxidative stress related biomarker levels at the end point of the experiment. Mechanistically, studies showed that NGEN markedly reduced lipid and protein oxidations, recruited the anti-oxidative defense system and promoted extracellular matrix degradation by modulating the levels of necrotic inflammation.

Flax and Pumpkin seeds mixture ameliorates diabetic nephropathy in rats

This study investigated the hypoglycemic and antioxidant effects of Flax and Pumpkin seeds mixture on the kidney of alloxan-induced diabetic rats. Animals were allocated into three groups of six rats each: a control group (CD), a diabetic group (DD) and diabetic rats fed with Flax and Pumpkin seeds mixture (DMS) group. The DD rats showed a significant increase of glycemia and lipid parameters such as total lipid, total cholesterol and triglycerides levels compared to those of the control group (CD). In addition, plasma and kidney malonaldialdehyde levels (MDA) were significantly increased compared to (CD) group. Antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD) and non-enzymatic levels of reduced glutathione (GSH) significantly decreased in the plasma and kidney of diabetic rats compared to those of controls. Diet supplemented with Flax and Pumpkin seeds mixture ameliorated the antioxidant enzymes activities observed in diabetic rats and significantly decreased MDA levels. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In DMS rats, these histopathological changes were less prominent. Our results suggest that Flax and Pumpkin seeds mixture supplemented in diet of diabetic rats may be helpful to prevent diabetes and its complications.

Protective role of naringin against cisplatin induced oxidative stress, inflammatory response and apoptosis in rat striatum via suppressing ROS-mediated NF-κB and P53 signaling pathways

Cisplatin (Cis) is an effective chemotherapeutic agent successfully used in the treatment of a wide range of malignancies while its usage is limited due to its dose-dependent toxicity. The present study was conducted to investigate the efficacy of naringin, an ubiquitous flavonoid, against Cis-induced striatum injury in Wistar aged rats. Briefly, the experimental procedures were divided in two sets of experiments. In the first, the animals were divided into 4 groups: control, Nar 25mg/kg, Nar 50mg/kg and Nar 100mg/kg. In the second, the animals were divided into 4 groups: Cis (5mg/kg/week for 5 consecutive weeks), Cis+Nar (25mg/kg), Cis+Nar (50mg/kg) and Cis+Nar (100mg/kg). The administration of Cis (5mg/kg/week for 5 consecutive weeks) resulted in a decline in the concentrations of reduced glutathione and ascorbic acid. The activity of membrane bound ATPases and glutathione peroxidase (GPx) were decreased while the activity of catalase (CAT) and superoxide dismutase (SOD) were increased. Further, in striatum tissue, Cis significantly enhance the mRNA gene expression of P53, nuclear factor κB pathway (NFκB) and tumor necrosis factor (TNF-α). Oxidative/nitrosative stress was evident in Cis group by increased malondialdehyde (MDA), protein carbonyls (PCO), reactive oxygen species (ROS) and nitrite concentration (NO). Naringin (25, 50 and 100mg/kg) administration was able to protect against deterioration in striatum tissue, abrogate the change in antioxidant enzyme activities and suppressed the increase in MDA, PCO, NO and TNF-α concentrations. Moreover, Nar inhibited P53, NFkB and TNF-α pathways mediated inflammation and apoptosis, and improved the histological changes induced by Cis. Thus, these findings demonstrated the neuroprotective nature of Nar by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in striatum tissue. These results imply that Nar has perfect effect against Cis-induced striatum injury in aged rats, which should be developed as an effective food and healthcare product for the treatment of brain injury in the future.