Hematological effects of arsenic in rats after subchronical exposure during pregnancy and lactation: The protective role of antioxidants

Free radicals production is involved in the toxicity of arsenic. The aim of this study was to determine whether biochemical changes occurred in the blood of arsenic-exposed pups during gestation and lactation, and additionally to investigate the potential beneficial role of the administration of certain antioxidants against arsenic exposure damage. Pregnant wistar rats received the following treatments as drinking water: (1) distilled water; (2) arsenic (50 mg/L); (3) antioxidants: zinc (20 mg/L) + vitamin C (2 g/L) + vitamin E (500 mg/L); (4) arsenic (50 mg/L) + antioxidants: zinc (20 mg/L) + vitamin C (2 g/L) + vitamin E (500 mg/L). We found a normocytic and normochromic anemia as well as a significant increase in hemolysis, TBARS production and catalase activity in the blood of arsenic intoxicated pups. Moreover, this metalloid produced a significant increase of serum cholesterol, triglicerids and urea levels whereas the proteins diminished. These effects were palliated in some extent by the coadministration of vitamins and zinc. Our findings suggest that administration of antioxidants during gestation and lactation could prevent some of the negative effects of arsenic.     

Effects of l-ascorbic acid on two cycles of cisplatin-induced DNA double-strand breaks and phosphorylation of p53 in the liver

Cisplatin, a commonly used anticancer drug, was studied to investigate its effects on structure, DNA damage and p53 along with the possible protective effects of l-ascorbic acid in the liver. Adult male BALB/c mice were treated with 0, 10 mg/kg l-ascorbic acid and two cycles of cisplatin 1 mg/kg/2.5 mg/kg with or without l-ascorbic acid (17 days recovery period between the cycles) and the livers were collected at 72 h after the last exposure. Structural damage was analyzed in Masson's trichrome and Hortega's silver stained liver tissues. The DNA double-strand breaks with duplex 3′ overhangs and 5′ P-blunt ends were labeled by in situ oligo ligation by using hairpin oligonucleotide probes. The expression of p53 and phosphorylated p53 (p-p53) was detected by immunohistochemistry. Structural changes such as vacuolization of hepatocytes, pyknosis, infiltration of leukocytes and pericentral fibrosis were observed without any protection from l-ascorbic acid. The reticular fibrous framework was affected and the incidence of Kupffer cells was decreased. Cisplatin induced the DNA double-strand breaks (p < 0.001); however, the latter appeared in a p53-independent, but p-p53-dependent manner. l-ascorbic acid showed significant protective effect on cisplatin-induced DNA damage (p < 0.001). Cisplatin also enhanced p53 phosphorylation in a dose-dependent manner and l-ascorbic acid reduced this biochemical change only in 1 mg/kg group. In conclusion, cisplatin-induced structural changes are not, but the DNA damage and phosphorylation of p53 are, significantly, but not completely, alleviated by l-ascorbic acid.     

High-dose vitamin C: Does it exacerbate the effect of psychosocial stress on liver? Biochemical and histological study

AimChronic stress has been implicated as a contributing factor in liver injury. However, other factors that can contribute to the severity of stress effect in liver injury have not been well characterized. In this study, the combined effect of chronic psychosocial stress and variable dosing levels of vitamin C on liver injury, have been studied.MethodsStress was chronically induced using intruder method. Vitamin C was administered by oral gavage. Both biochemical and histopathological measures were undertaken.ResultsThe results showed that low (50 mg/kg/day) and moderate (150 mg/kg/day) doses of vitamin C alone or in combination with chronic stress had no effect on liver. However, combination of high dose of vitamin C (500 mg/kg/day) and chronic stress induced various histopathological liver lesions in most of animals in the group that was stressed and supplemented with high dose vitamin C.ConclusionResults of this study show a dose-dependent effect for vitamin C in exacerbating stress contribution to liver injury.     

The potential role of combined antioxidant treatment on pancreas of STZ-diabetic mice

In diabetes, cells and tissues are damaged due to the imbalance between production of free radicals and removal of them. The effective biologic antioxidants for oxidative stress such as α-lipoic acid, vitamin E and selenium are effective in diminishing oxidative damage such as membrane lipid peroxidation. The experiment aimed to investigate the oxidative stress occurring in mitochondrial and cytoplasmic fraction of pancreatic tissues in streptozotocin-diabetic mice and the possible effects of α-lipoic acid + vitamin E + selenium combination on oxidative damage and antioxidative system by using microscopic and biochemical methods.The mice were divided into five groups. These groups were treated by citrate buffer, the solvents of the antioxidants, combined the antioxidants [α-lipoic acid (50 mg/kg), vitamin E (100 mg/kg), selenium (0.25 mg/kg)], streptozotocin (40 mg/kg × 5), combined the antioxidants and streptozotocin. The mice were sacrificed by cervical dislocation.In the experimental group given combined antioxidants following results were observed compared to diabetic group: increased percent insulin-positive cell area; decreased blood glucose levels; increased manganase superoxide dismutase activities and unsignificantly increased superoxide dismutase activities; unsignificantly decreased lipid peroxidase levels in both of fraction; unsignificantly decreased in mitochondrial fraction and unsignificantly increased in cytosolic fraction for catalase levels; not any alteration glutathione levels; not any activity in both of fraction for glutathione peroxidase.We can say that by taking the blood glucose levels and immunohistochemical results into account, the combination of triple antioxidants has a partly positive effect on diabetes. This positive effect could increase when trying different doses of combined antioxidant treatment.     

Protective effect of recombinant human erythropoeitin against cisplatin cytotoxicity and genotoxicity in cultured Vero cells

Cisplatin is an effective agent against various solid tumors. Despite its effectiveness, the dose of cisplatin that can be administered is limited by its nephrotoxicity. Therefore, strategies for minimising the toxicity of cisplatin are of a clinical interest. The aim of this study was to investigate the protective effect of recombinant human erythropoietin (rhEPO) against the cytotoxicity and apoptosis induced by cisplatin in cultured Vero cells. Three types of treatments were performed: (i) cells were treated with rhEPO 24 h before exposure to cisplatin (pre-treatment), (ii) cells were treated with rhEPO and cisplatin simultaneously (co-treatment), (iii) cells were treated with rhEPO 24 h after exposure to cisplatin (post-treatment). Our results showed that rhEPO reduced cisplatin-induced cell mortality. Besides, rhEPO administration prevented cisplatin-induced DNA damage. Furthermore, rhEPO decreased the caspase-3 activity and pro-apoptotic factors levels (p53 and Bax) induced by cisplatin. It increased also the expression of the anti-apoptotic factor Bcl2 in Vero cells. Altogether, our results suggest a protective action of rhEPO against cisplatin cytotoxicity and genotoxicity via an anti-apoptotic process. The most protective effect was observed with rhEPO when it was administrated 24 h before cisplatin treatment.     

Dichlorvos-induced testicular toxicity in male rats and the protective role of vitamins C and E

Dichlorvos is an organophosphorus insecticide that is used worldwide for pest control in agriculture and household use. Vitamins C and E are potential antioxidants protecting cells from oxidative stress. Vitamin C + vitamin E, dichlorvos, a combination of vitamin C + vitamin E + dichlorvos, or corn oil (control) were given to rats via oral gavage for 7 weeks. Body and testis weights, sperm parameters, hormone levels, histo- and cytopathological changes in testes were investigated at the end of 24 h and the 4th and 7th weeks comparatively with the control group. Body and testis weights, sperm morphology, FSH, LH, and testosterone levels were decreased significantly at the end of 4th and 7th weeks in the dichlorvos- and vitamins + dichlorvos-treated groups. A statistically significant decline in sperm motility and testosterone levels occurred by the end of 7th week in the dichlorvos- and vitamins + dichlorvos-treated groups. Light and electron microscopy revealed necrosis, edema and cellular damage in testicular tissues of the dichlorvos- and vitamins + dichlorvos-treated rats at the end of 4th and 7th weeks. In conclusion, dichlorvos caused subacute and subchronic reproductive toxicity, but vitamins did not confer protection.     

Immunohistochemical and histological evaluations of cyclophosphamide-induced acute cardiotoxicity in wistar rats: The role of turmeric extract (curcuma)

Chemotherapy-induced cardiac derangement is a major concern in health sector. Cyclophosphamide as a chemotherapeutic agent induces acute cardiotoxicity through its toxic metabolite, acrolein. This study evaluated the effect of ethanol extract of turmeric on cyclophosphamide-induced acute cardiotoxicity in Wistar rats. Thirty-five healthy Wistar rats, weighing 200–250 g were randomly assigned into 7 groups (Groups A, B, C, D, E, F and G) N = 5. Group A was the control, group B was negative control, and group C was administered 200 mg/kg of turmeric extract (orally) only. While groups B, D, E, F and G were all administered 100 mg/kg cyclophosphamide (i.p) for 10 days. Groups D and E were administered 100 mg/kg and 200 mg/kg of turmeric extract (orally) respectively for 72 hours before cyclophosphamide administration. Groups F and G were concomitantly administered 100 mg/kg cyclophosphamide (i.p) with doses of 100 mg/kg and 200 mg/kg of turmeric extract (orally) respectively. The rats were sacrificed under ketamine anesthesia (30 mg/kg i.m). The left ventricle of the heart was excised. One-way ANOVA was used to analyze data. Results revealed that there was statistically significant (P < 0.05) difference in body weight change, CK–MB, and LDH across all experimental groups; which were significantly lower in cyclophosphamide group. Histology and Immunohistochemistry revealed that there were morphological alterations in the myocardium of the left ventricle in group B while turmeric extract ameliorated cyclophosphamide-induced damage in the myocardium in other experimental groups. In conclusion, cyclophosphamide-induced myocardial alterations were significantly ameliorated through administration of ethanol extract of turmeric.     

Genotoxic and mutagenic effects of fipronil on mice

The toxic effects of several compounds on ecosystems are not restricted to ecological disturbances, and may also affect long-term human health. Fipronil is highly efficient in the control of pests, including those resistant to pyrethroid, organophosphate, and carbamate insecticides. Relatively little is known about the action of fipronil in vertebrates. This study was aimed to evaluate the genotoxic and mutagenic potential of this compound in mice exposed to different doses and demonstrates the damage caused by fipronil on non-target organisms in artificial conditions. Mice were divided into five groups: group I = 30% of DL₅₀ (15 mg/kg), group II = 50% of the DL₅₀ (25 mg/kg), group III = DL₅₀ (50 mg/kg), group IV = negative control, and group V = positive control. Peripheral blood was collected for the comet assay (24 h after exposure) and the micronucleus test (24, 48 and 72 h after exposure). Our findings revealed that doses of 15 mg/kg (group I) and 25 mg/kg (group II) of fipronil did not have genotoxic or mutagenic effects. Only the highest dose tested (50 mg/kg) induced DNA damage 24 h after exposure, indicating the mutagenic potential of fipronil. Therefore, this or higher doses are not recommended, as they may be toxic to non-target organisms.     

Effect of quercetin against dichlorvos induced nephrotoxicity in rats

This study was carried out to determine the effect of quercetin against renal injury induced by dichlorvos (DDVP) in rats. Rats were randomly assigned to control, DDVP-treated (7.2 mg/kg bw), three different doses of quercetin-treated (2 mg/kg bw, 10 mg/kg bw, 50 mg/kg bw) and different doses of quercetin plus DDVP-treated groups. DDVP was administered daily to rats through their drinking water, and quercetin was administered by intragastric gavage for 90 days. By the end of the 90th day in the DDVP-treated group, the following indices significantly increased compared with the control (P < 0.01): activities of catalase, glutathione peroxidase and superoxide dismutase; level of malondialdehyde in kidney tissues; serum levels of creatinine and urea nitrogen; and level of β2-microglobulin, level of retinol-conjugated protein, and activity of N-acetyl-β-d-glucosaminidase in urine; by contrast, urine uric acid levels significantly decreased. However, in the quercetin (50 mg/kg bw) plus DDVP group, the aforementioned indices were significantly decreased compared with the DDVP-treated group (P < 0.05), except the urine uric acid levels were significantly increased (P < 0.05). Thus, rat exposure to DDVP caused renal injury, including renal tubular, glomerular filtration, and oxidative stress. These toxic effects were also regulated by high-dose quercetin. Histopathological examination revealed that exposure to DDVP induced extensive cell vacuolar denaturation, but milder histopathological alterations in the kidney tissues of rats co-treated with DDVP and quercetin (50 mg/kg bw) were observed. These results indicated that quercetin at 50 mg/kg bw can partly prevent the kidney injury induced by DDVP.     

Protective effects of fullerenol C60(OH)24 against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer

The effects of fullerenol C₆₀(OH)₂₄ (Frl) at doses of 25, 50, and 100 mg/kg/week (for a time-span of 3 weeks) on heart and liver tissue after doxorubicin (Dox)-induced toxicity in rats with colorectal cancer were investigated. In the present study, we used an in vivo Wistar male rat model to explore whether Frl could protect against Dox-induced (1.5 mg/kg/week for 3 weeks) chronic cardio- and hepato- toxicity and compared the effect with a well-known antioxidant, vitamin C (100 mg/kg/week for 3 weeks). According to macroscopic, microscopic, hematological, biochemical, physiological, pharmacological, and pharmacokinetic results, we confirmed that, at all examined doses, Frl exhibits a protective influence on the heart and liver tissue against chronic toxicity induced by Dox.     

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.     

Efficacy of vitamin C against liver and kidney damage induced by paraquat toxicity

Paraquat has been demonstrated to be a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades. The current experiment aimed to examine if vitamin C (ascorbic acid) alleviates the morphological changes induced by paraquat (PQ) administration in the liver and kidney of male albino rats. Male adult rats received paraquat (PQ) (1.5 mg/kg body weight) daily for three weeks. Vitamin C (VC) at a dose of 20 mg/kg body weight was given concomitantly with PQ to rats. Animals were divided into three groups in this experiment (control, PQ and PQ + VC). The morphopathological manifestations were investigated in tissues from liver and kidney. As expected, PQ administration induced marked changes in the morphological structure of the liver and kidney in PQ demonstrated animals. Importantly, vitamin C administration restored PQ-induced changes in the studied organs. Vitamin C administration attenuated the morphological damages induced by PQ in the liver and kidney of experimental animals. Our results suggest an antitoxic effect of vitamin C against paraquat.     

The protective effects of vitamin C on the DNA damage,antioxidant defenses and aorta histopathology in chronic hyperhomocysteinemia induced rats

The aim of this study was to investigate the protective effect of vitamin C towards hyperhomocysteinemia (hHcy) induced oxidative DNA damage using the comet assay. The increase in plasma homocysteine levels is an important risk factor for vascular and cardiovascular diseases through free radical production. This study was also conducted to investigate the histopathological changes in the thoracic aorta and the oxidant/antioxidant status in heart, liver and kidney tissues.Twenty-four adult male Wistar rats were divided as control, hHcy and hHcy + vitamin C group. Chronic hHcy was induced by oral administration of l-methionine (1 g/kg/day) for 28 days. Vitamin C was given 150 mg/kg/day within the specified days. DNA damage was measured by use of the comet assay in lymphocytes. Levels of malondialdehyde (MDA) and glutathione (GSH) as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in heart, liver and renal tissues.Results show that l-methionine administration significantly increased % Tail DNA and Mean Tail Moment in hHcy group as compared with other groups. Vitamin C treatment significantly decreased the high MDA levels and increased activity of antioxidant enzymes in tissues. Aortic diameter and thickness of aortic elastic laminae were significantly lower in hHcy + vitamin C group.Comet assay can be used for the assessment of primary DNA damage caused by hHcy. Histopathological findings showed that vitamin C may have a preventive effect in alleviating the negative effects of hHcy. Vitamin C might be useful in the prevention of endothelial dysfunction caused by hHcy.     

Furan-induced dose–response relationships for liver cytotoxicity,cell proliferation,and tumorigenicity (furan-induced liver tumorigenicity)

Rodent studies of furan are associated with liver cell necrosis, release of liver-associated enzymes, increased hepatocyte proliferation, and hepatocarcinogenesis. For carcinogens whose proposed mode of action is cytolethality, it is hypothesized that the dose–response curve for tumor development would parallel the dose–response curve for cell death with compensatory proliferation in the target organ. To prospectively test this hypothesis, female B6C3F₁ mice were exposed to furan at carcinogenic doses and lower for 3 weeks or 2 years. At 3 weeks and in the 2-year study, there were dose-dependent and significant increases in hepatic cytotoxicity at 1.0, 2.0, 4.0, and 8.0 mg furan/kg. For cell proliferation as measured by 5-bromo-2′-deoxyuridine (BrdU) labeling index (LI), there was a statistically significant trend with increasing dose levels of furan and increased LI at 8.0 mg/kg. There was an increased incidence of foci of altered hepatocytes, hepatocellular adenomas, and adenomas or carcinomas at 4.0 and 8.0 mg/kg and carcinomas at 8.0 mg/kg. The multiplicity of microscopic tumors was increased and latency was decreased in mice exposed to 8.0 mg/kg. Prevalence of hepatic nodules at necropsy was increased in mice exposed to 4.0 and 8.0 mg/kg. Data demonstrate an association among furan-induced hepatic cytotoxicity, compensatory cell replication, and liver tumor formation in mice; at high doses ?4.0 mg/kg, furan induced hepatotoxicity, compensatory cell replication and tumorigenesis in a dose-related manner, while furan did not produce tumors at cytotoxic doses of 1.0 and 2.0 mg/kg.     

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.     

Antioxidant effects of Citharexylum spinosum in CCl4 induced nephrotoxicity in rat

The present study was carried out to evaluate the antioxidant effect of the chloroform extract of Citharexylum spinosum (CSCE) (Family: Verbenaceae) leaves in Sprague–Dawley male rats. The different groups of animals were administered with carbon tetrachloride (CCl₄; 20% in olive oil, 2 ml/kg body weight) 7 doses (i.p.) at 48 h interval. The CSCE at the doses of 100 and 200 mg/kg or silymarin at a dose of 50 mg/kg were administered intragastrically after 24 h to the CCl₄ treated rats. The effect of CSCE or silymarin on urine and serum markers (urea, creatinine, creatinine clearance, protein, albumin, urobilinogen and nitrite) was measured in CCl₄-induced nephrotoxicity in rat. Further, the effects on lipid peroxidation (TBARS), enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase) and non-enzymatic antioxidant glutathione (GSH) were estimated in the kidney samples. The CSCE and silymarin produced significant renal protective effects by restoring the concentration of urine and serum markers. Activity level of antioxidant enzymes and GSH contents were increased while lipid peroxidation (TBARS) was decreased, dose dependently with CSCE and silymarin. Decrease in body whereas increase in kidney weight induced with CCl₄ was restored with CSCE and silymarin. Chemical composition of CSCE indicated the presence of flavonoids, terpenoids, alkaloids and very low amount of saponins. Total flavonoids estimated were (127 ± 14.6) as rutin equivalent mg/g of the extract. From these results, it is suggested that CSCE possesses potent nephroprotective and antioxidant properties.     

Dual effects of l-3,4-dihydroxyphenylalanine on aromatic l-amino acid decarboxylase,dopamine release and motor stimulation in the reserpine-treated rat: evidence that behaviour is dopamine independent

The comparative effects of l-3,4-dihydroxphenylalanine (L-DOPA) on dopamine synthesis, release and behaviour were studied in the reserpine-treated rat. Acute administration of L-DOPA (25–200 mg/kg) dose-dependently inhibited the activity of aromatic l-amino acid decarboxylase (AADC) in the substantia nigra and corpus striatum. The antiparkinsonian drugs budipine (10 mg/kg) and amantadine (40 mg/kg) enhanced AADC activity in these regions, and prevented or reversed AADC inhibition by L-DOPA. Dual probe dialysis revealed that low doses of L-DOPA (25–50 mg/kg) dose-dependently stimulated the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in nigra and striatum, whilst high doses of L-DOPA (100–200 mg/kg) completely suppressed the release of dopamine, but not DOPAC. Sulpiride (50 μM) administered via the probes antagonized dopamine release in response to 25 mg/kg L-DOPA, but greatly facilitated release by 200 mg/kg L-DOPA. Dopamine release was blocked by the centrally acting AADC inhibitor NSD 1015, but facilitated by the central AADC activator budipine. In behavioural tests L-DOPA (plus benserazide, 50 mg/kg) only reversed akinesia at 200 mg/kg, and not at 25–100 mg/kg. Pretreatment with either NSD 1015 (100 mg/kg) or budipine (10 mg/kg) markedly potentiated the motor stimulant action of a threshold dose of L-DOPA (100 mg/kg). A combination of NSD 1015 (100 mg/kg) and benserazide (50 mg/kg) potentiated L-DOPA behaviour more effectively than either inhibitor alone. NSD 1015-facilitated L-DOPA behaviour was antagonized by sulpiride (100 mg/kg) and not by SCH 23390 (1 mg/kg), whereas budipine-facilitated L-DOPA behaviour was fully antagonized by SCH 23390 and only partially by sulpiride.These results show that behaviourally active doses of L-DOPA in the reserpinized rat are not accompanied by significant increases in extracellular dopamine and are therefore probably not dopamine mediated. We propose that L-DOPA is capable of directly stimulating dopamine D₂ and possibly non-dopamine receptors, thereby inhibiting dopamine efflux presynaptically and promoting motor activation postsynaptically. A stimulant action of L-DOPA on motor behaviour, preferentially mediated by D₁>D₂ receptors, suggests that L-DOPA may also be capable of yielding a dopamine-like response in the absence of detectable dopamine release. These findings are incorporated into a new model of L-DOPA's actions in the reserpinized rat, and their possible implications for our understanding of L-DOPA in Parkinson's disease are discussed.     

Dose-dependent hepatoprotective effect of emodin against acetaminophen-induced acute damage in rats

Protective effect of emodin (1,3,8-trihydroxy-6-methyl anthraquinone), an active compound of Ventilago madraspatana Gaertn., was evaluated against acetaminophen-induced biochemical and histological alterations in rats. Acetaminophen (2 g/kg, po) administration caused significant elevation in the release of serum transaminases, alkaline phosphatase, lactate dehydrogenase, serum bilirubin and serum protein with concomitant decrease in hemoglobin and blood sugar after 24 h of its administration. Toxicant exposure intensified the lipid peroxidation and altered glutathione status, activities of adenosine triphosphatase, acid phosphatase, alkaline phosphatase as well as major cellular constituents i.e., protein, glycogen and total cholesterol in liver and kidney. Treatment of emodin (20, 30 and 40 mg/kg, po) significantly lessened the toxicity by protecting acetaminophen-induced alterations in various blood and tissue biochemical variables after 24 h of its administration. Acetaminophen administration initiated histological damage in liver. Some degree of protection was seen after emodin therapy in a dose-dependent manner. Emodin at doses of 30 and 40 mg/kg effectively reversed toxic events induced by acetaminophen as same as silymarin (50 mg/kg, po). Thus, the study concluded that emodin at a dose of 30 mg/kg (po) possesses optimum hepatoprotective ability against acetaminophen-induced toxicity.     

Vitamin E can improve behavioral tests impairment,cell loss,and dendrite changes in rats’ medial prefrontal cortex induced by acceptable daily dose of aspartame

Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100 mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200 mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7–61% in the rats treated with aspartame. However, neurons’ number, glial cells number, and rats’ performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame + vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E + aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes.     

Kenaf seed supercritical fluid extract reduces aberrant crypt foci formation in azoxymethane-induced rats

Kenaf (Hibiscus cannabinus) a plant of the family Malvaceae, is a valuable fiber plant native to India and Africa. Kenaf seeds contain alpha-linolenic acid, phytosterol such as β-sitosterol, vitamin E and other antioxidants with chemopreventive properties. In the present study we examined the hypothesis that kenaf seed ‘supercritical fluid extract’ (SFE) extract could suppress the early colon carcinogenesis in vivo by virtue of its bioactive compounds. To accomplish this goal, 60 male rats were randomly assigned to 5 groups which were (1) negative control group [not induced with azoxymethane (AOM)]; (2) positive control group (induced with AOM but received no treatment); (3) group treated with 500 mg/kg kenaf seed SFE extract; (4) group treated with 1000 mg/kg kenaf seed SFE extract; (5) group treated with 1500 mg/kg kenaf seed SFE extract. At 7 weeks of age, all rats except the negative control group received 15 mg/kg of AOM injection subcutaneously once a week for 2 weeks. Rats were euthanized at 13 weeks of the experiment. Number of ACF (mean ± SD) ranged from 84.4 ± 4.43 to 179.5 ± 12.78 in group 2, 3, 4, 5. ACF reductions compared with the untreated group were 45.3, 51.4 and 53.1% in rats fed with 500, 1000 and 1500 mg/kg body weight, respectively. There were no significant differences in weight gain among groups. Our finding indicates that kenaf seed SFE extract reduced AOM-induced ACF in Sprague–Dawley male rats.