Cobalt chloride induces hepatotoxicity in adult rats and their suckling pups

To assess liver damages in pregnant and lactating rats and in their suckling pups, wistar female rats were given through drinking water 350 ppm of CoCl₂ (157 ppm Co²⁺) from the 14th day of pregnancy until day 14 after delivery. The effects of cobalt chloride on lipid peroxidation levels, antioxidant enzyme activities, lipid profile and histopathology aspects of liver were evaluated. Biochemical results showed that lipid peroxidation increased significantly in Co-treated rats, as evidenced by high liver thiobarbituric acid-reactive substance (TBARS) levels. Alteration of the antioxidant system in treated group was confirmed by the significant decline of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and reduced glutathione (GSH) content in liver of suckling pups and their mothers. Moreover, CoCl₂ exposure induced an increase in the activities of the aspartate transaminase (AST), alanine transaminase (ALT), lactate deshydrogenase (LDH) and bilirubin levels in pups and their mothers while liver LDH activity and plasma albumin level were significantly decreased. On the other hand, cobalt chloride induced a marked hypoglycemia, a significant decline in triglycerides and total cholesterol levels. Histological studies showed an infiltration of mononuclear cells and vascular congestion in liver of pups and their mothers.Based on the present findings, exposure of rats to CoCl₂ during late pregnancy and early postnatal period affects antioxidant enzyme activities and lipid peroxidation indicating liver damage in mothers and their offspring.     

Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage

The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4 ± 1.9 mg GAE/g), condensed tannins (58.4 ± 2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe²⁺-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE + Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption.     

Protective effect of curcumin on cypermethrin-induced oxidative stress in Wistar rats

The aim of present study was to investigate the protective effect of curcumin on cypermethrin-induced changes in blood biochemical markers and tissue antioxidant enzyme in rats. Rats were divided into six groups of six each: group I used as control and II and III groups were used as vehicle control. While, groups IV, V and VI were orally treated with curcumin (100 mg/kg body weight), cypermethrin (25 mg/kg body weight) and cypermethrin plus curcumin, respectively for 28 days. Serum biochemical markers were measured in the serum, and the levels of lipid peroxidation and antioxidant enzyme activity were determined in the liver, kidney and brain. Cypermethrin administration caused elevated level of blood biochemical markers in serum and lipid peroxidation in liver, kidney and brain. While the activities of non-enzymatic and enzymatic antioxidants levels were decreased except superoxide dismutase in liver, kidney and brain tissues. The presence of curcumin with cypermethrin significantly decreased the blood biochemical markers and lipid peroxidation but significantly increased the reduced glutathione, catalase and glutathione peroxidase level and preserved the normal histological architecture of the liver, kidney and brain. Our results indicate that curcumin can be potent protective agent against cypermethrin-induced biochemical alterations and oxidative damage in rats.     

Nephrotoxic effect of tetradifon in rats: A biochemical and histomorphometric study

The effects of subchronic exposure to tetradifon on biochemical related kidney toxicological parameters [creatinine (CRT), urea, and uric acid (UA)] were examined. Oxidative stress in kidney tissue was also assessed by measuring vitamin C (VitC) content and antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)]. Tetradifon was administered orally to 12 rats at a cumulative dose of 24.3 mg/kg for 12 weeks. Twelve additional rats, no treated, have served as control. Control and treated animals were sacrificed after 6 or 12 weeks. For each group, kidneys were examined for morphometric changes. Results showed that tetradifon induced significant increases in CRT and urea, and decrease in UA. Morphometrically, while mean glomerular volume decreased percentage of sclerosed glomeruli increased in treated rats. Index of interstitial fibrosis was significantly higher. Moreover, renal antioxidant enzyme (SOD and GPx) activities and VitC content decreased. We concluded that tetradifon possessed nephrotoxic by promoting kidney morphometric and functional damage and depleting renal antioxidant defense system in rats.     

Hepatoprotective effect of chitosan-caffeic acid conjugate against ethanol-treated mice

The chitosan-caffeic acid (CCA) conjugate shows a hepatoprotective effect against oxidative stress-induced hepatic damage in cultured hepatocytes. The objective of this study is the verification of the hepatoprotective effect of the CCA in vivo against ethanol-induced liver injury in mice. The administration of ethanol resulted in the increase of the serum-aminotransferase activities (AST and ALT), triglycerides, total cholesterol, and lipid peroxidation. The CCA co-administration, however, significantly (p < 0.05) ameliorated these serum biomarkers. The antioxidant-enzyme activities in the liver tissue, including those of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were significantly decreased by a chronic ethanol administration, whereas the hepatic lipid-peroxidation level was increased. Moreover, the chronic ethanol administration elevated the gene expression of pro-inflammatory cytokines such as tumor-necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the liver tissue. The CCA co-administration, however, significantly (p < 0.05) increased the activities of the SOD, CAT, and GPx and caused the down-regulation of the TNF-α- and IL-6-gene expressions in the liver tissue. An histopathologic evaluation also supported the hepatoprotective effect of the CCA against ethanol-induced hepatotoxicity in the mice.     

Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin

This experiment pertains to the protective role of naringenin against cadmium (Cd)-induced oxidative stress in the liver of rats. Cadmium is a major environmental pollutant and is known for its wide toxic manifestations. Naringenin is a naturally occurring citrus flavonone which has been reported to have a wide range of pharmacological properties. In the present investigation cadmium (5 mg/kg) was administered orally for 4 weeks to induce hepatotoxicity. Liver damage induced by cadmium was clearly shown by the increased activities of serum hepatic marker enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and serum total bilirubin (TB) along with the increased level of lipid peroxidation indices (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) and protein carbonyl contents in liver. The toxic effect of cadmium was also indicated by significantly decreased levels of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (reduced glutathione (GSH), vitamin C and vitamin E). Administration of naringenin at a dose of (50 mg/kg) significantly reversed the activities of serum hepatic marker enzymes to their near-normal levels when compared to Cd-treated rats. In addition, naringenin significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. The histopathological studies in the liver of rats also showed that naringenin (50 mg/kg) markedly reduced the toxicity of cadmium and preserved the normal histological architecture of the tissue. The present study suggested that naringenin may be beneficial in ameliorating the cadmium-induced oxidative damage in the liver of rats.     

Alcohol-induced oxidative stress in rat liver microsomes: Protective effect of Emblica officinalis

The protective effect of Emblica officinalis fruit extract (EFE) against alcohol-induced oxidative damage in liver microsomes was investigated in rats. EFE (250 mg/kg b.wt/day) and alcohol (5 g/kg b.wt/day, 20%, w/v) were administered orally to animals for 60 days. Alcohol administration significantly increased lipid peroxidation, protein carbonyls with decreased sulfhydryl groups in microsomes, which were significantly restored to normal levels in EFE and alcohol co-administered rats. Alcohol administration also markedly decreased the levels of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in the liver microsomes, which were prevented with EFE administration. Further, alcohol administration significantly increased the activities of cytochrome P-450, Na⁺/K⁺ and Mg²⁺ ATPases and also membrane fluidity. But, administration of EFE along with alcohol restored the all above enzyme activities and membrane fluidity to normal level. Thus, EFE showed protective effects against alcohol-induced oxidative damage by possibly reducing the rate of lipid peroxidation and restoring the various membrane bound and antioxidant enzyme activities to normal levels, and also by protecting the membrane integrity in rat liver microsomes. In conclusion, the polyphenolic compounds including flavonoid and tannoid compounds present in EFE might be playing a major role against alcohol-induced oxidative stress in rats.     

Kidney antioxidant status,biochemical parameters and histopathological changes induced by methomyl in CD-1 mice

The widespread of pesticide in public health and agriculture has caused severe environmental pollution and health hazards. Methomyl is used worldwide in agriculture and health programs. Besides its advantages in the agriculture, it causes several toxic effects. In this study, we aimed to investigate the effects of methomyl at different time intervals on lipid peroxidation, reduced glutathione (GSH), total sulfhydryl group (T-SH), antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and histopathological changes in mice kidney. Ten CD-1 mice per group were assigned to one of four treatment groups. Group one served as control while groups 2, 3 and 4 were orally treated with 1 mg methomyl/kg BW for 10, 20 and 30 days, respectively. Methomyl significantly increased lipid peroxidation in kidney as compared to control group. Levels of GSH and T-SH and activities of SOD, CAT and GST were found to be decreased. On the other hand, methomyl significantly increased the levels of urea, uric acid and creatinine in serum. The histological examination of kidney revealed damage involving the entire renal nephrons in both 20 and 30 days of methomyl exposure. Severe dilatation of the cortical tissue, congested glomerulus with swelling of the endothelial cells and degeneration of the epithelium cells lining the tubules were observed. In conclusion, the results suggest that methomyl exposure can cause renal damage, oxidative stress, perturbations in antioxidant defense system and histopathologic changes in mice kidney in a time dependent manner.     

Oral administration of caffeic acid ameliorates the effect of cisplatin on brush border membrane enzymes and antioxidant system in rat intestine

Cisplatin (CP) is a widely used antineoplastic drug that exhibits gastrointestinal toxicity. We have previously shown that administration of a single dose of CP results in a decrease in the activities of several brush border membrane (BBM) enzymes, induces oxidative stress and alters the activities of several antioxidant enzymes in the small intestine of rats. In the present study we have investigated the effect of treatment with the dietary antioxidant caffeic acid (CA) on CP induced biochemical changes in the intestine. Administration of a single intraperitoneal dose of CP alone (6 mg/kg body weight) led to a decrease in the activities of the BBM enzymes, increase in lipid peroxidation, decrease in sulfhydryl groups and changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, glucose 6-phosphate dehydrogenase, glutathione reductase, glutathione S-transferase and thioredoxin reductase. Administration of two doses of CA (each of 250 mg/kg body weight), at 15 and 120 min after treatment with CP, significantly attenuated the CP-induced changes in all these parameters but the administration of CA alone had no effect. These results suggest that CA is an effective agent in reducing the effects of CP on the intestine and could prove to be useful in alleviating the gastrointestinal toxicity of this drug.     

Influence of rutin on biochemical alterations in hyperammonemia in rats

Flavonoids are non-nutritive dietary components that are widely distributed in plants. The present study was undertaken to examine the protective influence of rutin, a polyphenolic flavonoid, on oxidative stress during ammonium chloride (AC)-induced hyperammonemia by measuring the levels of oxidative damage as well as antioxidant status. The levels of tissue (liver, brain and kidney) lipid peroxides and the antioxidants (total thiols, catalase, reduced glutathione and glutathione peroxidase) were analyzed. Hyperammonemia was induced by daily intraperitoneal injections of AC at a dose of 100 mg/kg body weight for 8 weeks. Decreased levels of tissue lipid peroxidation accompanied with increased antioxidant levels in hyperammonemic rats were observed during oral administration of rutin (50 mg/kg body weight), which clearly shows the antioxidant property of rutin. The study of induction of the antioxidant status is considered to be a reliable marker for evaluating the antiperoxidative effect of the polyphenolic compound. Our present findings show the protective role of rutin against lipid peroxidation and suggest that rutin possesses antioxidant potential that may be used for therapeutic purposes.     

Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats

The present study was to evaluate the hepatoprotective effect of hesperetin (HTN) on cadmium (Cd) induced hepatotoxicity in male Wistar rats. Administration of Cd (3 mg/kg body weight/day) subcutaneously for 21 days, the levels of hepatic markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and bilirubin were significantly increased in serum. The levels oxidative stress markers, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), conjugated dienes (CD) and protein carbonyl content (PCC) were also significantly increased while the levels of vitamin C, vitamin E, reduced glutathione (GSH), total sulphydryl group (TSH) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) were significantly decreased in the liver of Cd intoxicated rats. HTN, a flavanone in citrus fruits, administrated orally along with Cd injection for 21 days, significantly revert back the status of serum hepatic markers, oxidative stress markers and antioxidant markers in the liver tissue to near normal level in a dose dependent manner. HTN at a dose of 40 mg/kg body weight/day exhibits significant (p < 0.05) hepatoprotection compared with other two doses (10 and 20 mg/kg body weight/day). The histopathological studies in the liver of rats also supported that HTN (40 mg/kg) markedly reduced the toxicity of Cd and preserved the histoarchitecture of the liver tissue to near normal. Thus, the results suggest that HTN acts as a potent hepatoprotective agent against Cd induced hepatotoxicity in rats.     

Effects of captopril on the cysteamine-induced duodenal ulcer in the rat

Oxidative stress is important factor underlying in a variety of diseases. Antioxidative enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) are part of the physiological defenses against oxidative stress. Malondialdehyde (MDA) is a lipid peroxidation biomarker and its elevated level in various diseases is related to free radical damage. Cysteamine is a cytotoxic agent, acting through generation of reactive oxygen species (ROS) and may decrease defense activity of antioxidative enzymes against ROS and induce duodenal ulcer. Captopril, acts as free radical scavengers and protect against injuries from oxidative damage to tissues.The aim of this study was the evaluation of the effect of captopril against cysteamine-induced duodenal ulcer by determining duodenal damage, duodenal tissue SOD and GSH-PX activities and plasma MAD level. This study was performed on 3 groups of 7 rats each: saline, cysteamine and cysteamine plus captopril treated groups. The effect of captopril against cysteamine-induced duodenal ulcer is determined by evaluating the duodenal damage, duodenal tissue SOD and GSH-PX activities and plasma MDA level. All animals were euthanized 24 h after the last treatment and 2 ml blood and duodena samples were collected for calculation of ulcer index, histopathological assessment and measurement of tissue SOD, GSH-PX activities and plasma MDA level.Cysteamine produced severe duodenal damage, decreased the activity of duodenal tissue SOD and GSH-PX and increased the plasma MDA level compared with saline pretreated rats. Pretreatment with captopril decreased the cysteamine-induced duodenal damage and plasma level of MDA and increased the activities of SOD and GSH-PX in duodenal tissue compared with cysteamine pretreated animal. Our results suggest that captopril protects against cysteamine–induced duodenal ulcer and inhibits the decrease in SOD and GSH-PX activities and lipid peroxidation by increasing antioxidant defenses.     

Quercetin protects against oxidative stress-related renal dysfunction by cadmium in rats

The aim of this study was to investigate the possible protective role of the dietary flavonoid quercetin on cadmium (Cd)-induced nephrotoxicity using biochemical and histopathological approaches. In experimental rats oral administration of CdCl₂ (5 mg/kg) for 4 weeks significantly induced renal damage which was evident from the increased levels of serum urea, uric acid and creatinine with a significant (p<0.05) decrease in creatinine clearance. Cd also significantly (p<0.05) decreased the levels of urea, uric acid and creatinine in urine. Cd-induced oxidative stress in kidney tissue was indicated by the increased levels of renal lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) and protein carbonyl content with a significant (p<0.05) decrease in non-enzymatic (total sulphydryl group, reduced glutathione, vitamin C and vitamin E) and enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose 6-phosphate dehydrogenase (G6PD)). Moreover the kidneys of Cd-treated rats showed tubular necrosis, degeneration, dilation, desquamation, thickening of basement membrane and luminal cast formation. Quercetin treatment markedly attenuated the Cd-induced biochemical alterations in serum, urine and renal tissue. Quercetin also ameliorated the Cd-induced pathological changes when compared with Cd-alone-treated group. These data indicate that the natural dietary antioxidant quercetin might have protective effect against Cd-induced nephrotoxicity and oxidative stress in rats.     

Pyrrolizidine alkaloid isoline-induced oxidative injury in various mouse tissues

Isoline is a retronecine-type pyrrolizidine alkaloid (PA) isolated from the traditional Chinese medicinal herb Ligularia duciformis. The present investigation was carried out to evaluate isoline-induced oxidative injury in various important mouse organs. Various tissue samples were collected after mice were administrated with 100 mg/kg isoline for 36 h, and then lipid peroxidation (LPO) level, total antioxidant capacity, glutathione-S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities were determined to evaluate the oxidative injury. Our results showed that the total antioxidant capacity of liver, brain and lung were all decreased after given isoline, and the LPO level was increased in liver and heart of isoline-treated mice. Further antioxidant-related enzyme activity assays showed that isoline (100 mg/kg) decreased GPx activity in liver and heart, increased CAT activity in liver, brain and heart, and decreased the GST activity in lung. Taken together, our results demonstrate that isoline can induce different oxidative injury in various important mouse organs, and of which liver is the most sensitive organ.     

Prevention of cisplatin induced nephrotoxicity by terpenes isolated from Ganoderma lucidum occurring in Southern Parts of India

Investigations were carried out to determine the protective effect of terpenes isolated from the fruiting bodies of Ganoderma lucidum (Fr) P.Karst against nephrotoxicity caused by the cisplatin, in mice. Intraperitoneal administration of cisplatin (16 mg/kg body wt) resulted in significant nephrotoxicity in mice. Serum urea, creatinine and ALP levels were drastically elevated indicating severe nephrotoxicity . The renal antioxidant defense system such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and concentration of reduced glutathione (GSH) were depleted by cisplatin injection. The oral administration of terpenes at a dose of 100 mg/kg body weight prevented increase in urea, creatinine levels and ALP activity and also maintained the renal antioxidant defense. The Ganoderma terpenes also imparted protection against cisplatin induced renal tissue lipid peroxidation. The results indicated that the total terpenes isolated from G. lucidum possessed significant in vivo antioxidant activity and rendered protection against cisplatin induced nephrotoxicity. The results suggest the potential therapeutic use of Ganoderma terpenes to prevent nephrotoxicity caused during chemotherapy using cisplatin.     

Oral phenytoin protects against experimental cyclophosphamide-chemotherapy induced hair loss

In the current study, effects of oral phenytoin on hair growth in cyclophosphamide-treated rats were assessed with the goal of evaluating the ability of phenytoin to suppress chemotherapy-induced hair loss. Thirty-six rats were randomly assigned to six groups (1k6) of six each (n = 6). In all groups, anagen was induced in flank skin of rats by depilation. On day 9 (anagen VI), rats were injected once with either distilled water (groups 1–3) or cyclophoshamide (groups 4–6). From day 10, rats in group 1 and 4 received oral vehicle (distilled water), groups 2 and 5 received oral phenytoin (50 mg/kg), while groups 3 and 6 also received oral phenytoin (100 mg/kg). Drug or vehicle was administered daily for a period of 28 days. The flank area was serially photographed. At the end of the experimental period, rats were sacrificed to correlate visible hair growth with a histological profile of follicle response and recovery. Glutathione (GSH), glutathione peroxidase (GPX) and lipid peroxidation status were assessed. Cyclophosphamide (CYP) treatment was associated with gross morphologic and histological evidence of hair loss in the flanks, microscopic evidence of hair-shaft thinning, increased skin lipid peroxidation, decreased GSH level, and reduction in GPX activities. Phenytoin co-administration was associated with evidence of improved hair growth, increased hair-shaft thickness, reduced skin lipid peroxidation, increased GSH level, and increased GPX activities. This study showed that oral phenytoin can suppress hair loss due to CYP therapy in rats; however, further studies are needed to evaluate its potential application in chemotherapy-induced alopecia.     

Impact of ellagic acid on adriamycin-induced testicular histopathological lesions,apoptosis, lipid peroxidation and sperm damages

The aim of the present study was to investigate whether ellagic acid (EA) has protective effect on adriamycin (ADR)-induced testicular and spermatozoal toxicity associated with the oxidative stress in male rats. Thirthy-two healthy 8-week-old male Sprague–Dawley rats were equally divided into four groups. The first (EA) group was treated with EA (2 mg/kg/every other day) by gavage. The second (ADR) group received ADR (2 mg/kg/once a week) intraperitoneally, while the combination of ADR and EA was given to the third (ADR + EA) group. The forth (control) group was treated with placebo. At the end of the 8-week treatment period, reproductive organ weights, epididymal sperm parameters, histopathological changes and apoptosis via Bax and Bcl-2 proteins, testicular tissue lipid peroxidation, and antioxidant enzyme activities, were investigated. ADR administration was determined to cause significant decreases in reproductive organ weights, epididymal sperm concentration and motility, plasma testosterone concentration, diameter of seminiferous tubules, germinal cell layer thickness, Johnsen's testicular score and Bcl-2 positive antiapoptotic cell rate, wherease it caused significant increases in level of lipid peroxidation and glutathione, catalase activity, abnormal sperm rates and Bax positive apoptotic cell rates along with degeneration, necrosis, immature germ cells, congestion and atrophy in testicular tissue when compared with the control group. EA administration to ADR-treated rats provided significant improvements in ADR-induced disturbed oxidant/antioxidant balance, decreased testosterone concentration, testicular apoptosis and mild improvements in the histopathological view of the testicular tissue. However, EA failed to improve decreased reproductive organ weights and deteriorated sperm parameters due to ADR administration. It is concluded that while ADR has direct or indirect (lipid peroxidation) negative effects on sperm structure and testicular apoptosis in rats, EA has protective effects on ADR-induced testicular lipid peroxidation and apoptosis.     

Neuroprotective and anti-stress effect of A68930 in acute and chronic unpredictable stress model in rats

The neurorescuing effect of A68930 (a potent selective D₁ agonist) and its role on the regulation of hypothalamus-pituitary-adrenal (HPA)-axis have been investigated. Acute (AS) and chronic unpredictable (CUS) stress models were used to evaluate the effect of A68930 on HPA-axis regulation in relation to the change in the fiber density and number of immunoreactive (ir) neurons of tyrosine hydroxylase (TH) and glucocorticoid receptor (GR) in the dopamine (DA) and GR rich brain regions in rats. CUS caused a significant decrease in the number of TH ir neurons in the striatum, medial forebrain bundle, ventral tegmental area and substansia nigra and GR in the cortex, striatum and hippocampus as compared to the non-stress controls (NS). Administration of A68930 (0.25 mg/kg i.p.) significantly normalized these CUS-induced alterations. We also examined the role of A68930 on stress-induced brain oxidative status. AS enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the cortex and striatum, while CUS reduced the activities of SOD and catalase (CAT) in the cortex, striatum and hippocampus, when compared with NS. Increased GSH-Px activity, with reduced glutathione and increased lipid peroxidation was observed in both AS and CUS in selected brain regions as compared to NS. Administration of A68930 normalized the antioxidant enzyme activities, replenished GSH and decreased the extent of lipid peroxidation. In conclusion, present findings suggest that the stress-induced immunoreactivity of TH and GR in distinct brain regions are modulated by A68930 leading to the normalization of HPA-axis response. Ours results show the therapeutic importance of DA D₁ agonist in stress-induced dopaminergic-related neurological disorders. A68930 also influenced the brain antioxidant machinery probably through the restoration of stress-induced changes in the dopaminergic system and its crosstalk with GR.     

Ameliorative effect of Opuntia ficus indica juice on ethanol-induced oxidative stress in rat erythrocytes

The aim of the present study was to investigate the efficacy of Opuntia ficus indica f. inermis fruit juice (OFIj) on reversing oxidative damages induced by chronic ethanol intake in rat erythrocytes. OFIj was firstly analyzed with HPLC for phenolic and flavonoids content. Secondly, 40 adult male Wistar rats were equally divided into five groups and treated for 90 days as follows: control (C), ethanol-only 3 g/kg body weight (b.w) (E), low dose of OFIj 2 ml/100 g b.w + ethanol (Ldj + E), high dose of OFIj 4 ml/100 g b.w + ethanol (Hdj + E), and only a high dose of OFIj 4 ml/100 g b.w (Hdj). HPLC analysis indicated high concentrations of phenolic acids and flavonoids in OFIj. Ethanol treatment markedly decreased the activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and the level of reduced glutathione (GSH). Changes in the erythrocyte's antioxidant ability were accompanied by enhanced oxidative modification of lipids (increase of malondialdeyde level) and proteins (increase in carbonyl groups). Interestingly, pre-administration of either 2 ml/100 g b.w or 4 ml/100 g b.w of OFIj to ethanol-intoxicated rats significantly reversed decreases in enzymatic as well as non enzymatic antioxidants parameters in erythrocytes. Also, the administration of OFIj significantly protected lipids and proteins against ethanol-induced oxidative modifications in rat erythrocytes. The beneficial effect of OFIj can result from the inhibition of ethanol-induced free radicals chain reactions in rat erythrocytes or from the enhancement of the endogenous antioxidants activities.     

Alterations in the erythrocyte antioxidant system of blood stored in blood bags

In the present study, we measured the concentrations of reduced glutathione (GSH) and malonyldialdehyde (MDA) and the activities of glutathione peroxidase (GSH-Px), glutathione S-transferase (GSH-S-T), superoxide dismutase (SOD), catalase (CAT) and glucose-6-phosphate dehydrogenase (G-6-PD) in erythrocytes obtained freshly from adult male donors which was preserved with CPDA-1 anticoagulant (citrate,phosphate, dextrose, adenine) on different days of storage. At the end of the study, storage-associated alterations in antioxidant activities were noted and discussed. GSH, GSH-Px, GSH-S-T, SOD, CAT and G-6-PD activities decreased, but erythrocyte MDA levels, as anindex of lipid peroxidation, increased during the storage period. According to our results, glutathione-dependent antioxidant systems in erythrocytes might be depleted during long storage in blood bags.