Role of Citrus medica L. Fruits Extract in Combatting the Hematological and Hepatic Toxic Effects of Carbofuran.

Citrus medica L. is rich in numerous vital bioactive constituents, though it is an underutilized among the citrus genus. Therefore, the aim of the present investigation was to evaluate the protective role of the C. medica fruit (CMF) methanol extract against carbofuran (CF)-induced toxicity in experimental rats. In addition, this work aims at detecting and measuring polyphenolic compounds by means of high-performance liquid chromatography (HPLC) and evaluation of the antioxidant activity of this extract. For this, studies dealing with serum hematological and biochemical parameters, liver endogenous antioxidants, as well as hepatic histo-architectural features have been carried out to assess the protective ability of CMF against CF-induced toxicity. Additionally, total phenol, flavonoid, and antioxidant capability were measured and the antioxidant action was investigated using DPPH and nitric oxide radical scavenging assays as well as reducing power assessments. HPLC results revealed the presence of benzoic acid, cinnamic acid, gallic acid, quercetin, and salicylic acid in CMF extract. Furthermore, results showed that CMF has considerable total phenol, flavonoid, and antioxidant capability and exhibits significant free radical scavenging and reducing potentialities. On the other hand, CF intoxication of rats significantly altered the hematological and serum biochemical parameters with hepatocytes disruption. Carbofuran also caused an upsurge in malondialdehyde (MDA) level and a decline in hepatic cellular antioxidant enzymes levels in rats compared to the control group. Co-administration of CMF amended the anomalies and improved the histo-architectural arrangement of hepatocytes in treated groups. CMF also inhibited the alteration of endogenous antioxidant enzymes and MDA levels as compared to the carbofuran treated group and returned them to their normal state. Taken all together, results from this investigation highlight the protective role of CMF against CF-induced toxicity which might be attributed to the polyphenolic constituents of the extract.

Effect of allicin on antioxidant defense system, and immune response after carbofuran exposure in Nile tilapia, Oreochromis niloticus.

In this work, allicin was evaluated as an immunostimulant and antioxidant agent preventing Nile tilapia; Oreochromis niloticus against carbofuran toxicity. Fish (60 ± 8 g) were allocated to five groups; the first group (control), the second group was fed 1 g/kg allicin-supplemented diets without carbofuran intoxication, the third group exposed to 1/10 LC50 carbofuran (0.246 mg/L). While the fourth, and fifth groups were fed allicin supplemented diet at concentration of 0.5 and 1 g/kg diet, respectively, and exposed to carbofuran at the same concentration similar to the one of the third group. After 30 days, fish exposed to carbofuran showed high ALT, AST, ALP, cholesterol, glucose, cortisol, uric acid, and creatinine levels. However, serum AChE, total proteins, immunoglobulins, and lysozyme activity were markedly (P ≤ 0.05) reduced in carbofuran exposed tilapia fish. Moreover, malondialdehyde (MDA) level was significantly increased in liver, and kidneys tissues of carbofuran exposed fish. Whereas, catalase (CAT) activity, superoxide dismutase (SOD), and total antioxidant capacity (TAC) were decreased (P ≤ 0.05) significantly in both liver, and kidneys tissues after exposure to carbofuran. Interestingly, tilapia fish treated with carbofuran (0.246 mg/L) and fed (0.5 and 1 g/kg diet) allicin in both the 4th & 5th groups, respectively, decreased serum biochemical parameters; and hepatorenal (MDA) levels, as well as increased AChE, immunological profile, and oxidative stress biomarkers. The results suggested that co- administration of allicin at the high dose is more capable of improving the biochemical, and immunological parameters, and tissue antioxidant responses of carbofuran treated fish.

Effect of kebar grass extract ( Biophytum petersianum Klotzsch) on histopathological changes in liver of mice offspring from the parent exposed to carbofuran during lactation period.

This study aims to determine the potential of Kebar grass extract in reducing the impact of liver damage in mice offspring ( Mus musculus) from parent exposed to carbofuran during lactation period. 42 lactation mice ( Mus musculus) used in the study were divided into seven groups, each group consisting of six mice. Carbofuran, Kebar grass extract, and vitamin C are administered orally on days 1 to 14 after birth. This group consisted of K (aquadest), P1 (carbofuran 1/4 LD50 0.0125 mg/day), P2 (carbofuran 1/8 LD50 0.00625 mg/day), P3 (Kebar grass extract 3.375 mg (0.2 ml) + carbofuran 1/4 LD50), P4 (Kebar grass extract 3.375 mg (0.2 ml) + carbofuran 1/8 LD50), P5 (vitamin C 5 mg (0.2 ml) + carbofuran 1/4 LD50), and P6 (vitamin C 5 mg (0.2 ml) + carbofuran 1/8 LD50). On the 15th day after birth, mice were sacrified and their liver taken for microscopic examination with hematoxilin and eosin staining. The scoring data were analyzed using Kruskal-Wallis and Mann-Whitney test. The result showed significant different (p⟨0.05) among the treatment groups. Mean of P4 in degeration is (1.13), necrosis (1.13) and inflamation (0.73), while the mean of P6 in degeneration is (2.20), necrosis (2.73) and inflamation (1.93). The conclusion of this research is giving Kebar grass extract is more effective in reducing degeneration, necrosis and inflammatory cell's infiltration than vitamin C in in mice offspring ( Mus musculus) from parent exposed to carbofuran during lactation period.

Comparative neuroprotective effects of native curcumin and its galactomannoside formulation in carbofuran-induced neurotoxicity model.

Toxicity of the pesticide carbofuran (CF) can be alleviated by curcumin, if not for its poor bioavailability. Hence, we investigated the effect of a bioavailable curcumin-galactomannan complex (CGM) on CF-induced neurotoxicity in rats in comparison to that of unformulated standard curcumin (CS). The CF (5 mg/kg b.wt/day) treatment for 90 days produced chronicity model which were treated with either CS or CGM (100 mg/kg b.wt and 250 mg/kg b.wt/day) for another 30 days. Improvement in CF-induced behaviour was evident in endurance, motor co-ordination and pain response on both CS (p < 0.01) and CGM (p < 0.001) supplementation. Amelioration of CF-induced toxicity parameters, oxidative stress, and mitochondrial dysfunction on CS (p < 0.01) and CGM (p < 0.001) supplementation was further confirmed by histopathology of brain and liver tissues. But, CGM was more effective in mitigating CF toxicity, with results comparable to that of normal. Hence, CGM might be superior in toxicity management against CF.

Hepatoprotective and Antioxidant Activities of Justicia gendarussa Leaf Extract in Carbofuran-Induced Hepatic Damage in Rats.

In folk medicines, Justicia gendarussa (J. gendarussa) is used as a depurative herb for treating fever, pain, and cancer and as laxative for constipation. The aim of the present investigation was to evaluate the hepatoprotective effect of the leaf methanol extract of J. gendarussa leaf (J gMe) against carbofuran (CF)-intoxicated liver injuries in Sprague-Dawley rats, along with the antioxidant activity of this extract. For this purpose, levels of serum diagnostic markers, hepatic antioxidant enzymes, and liver histo-architecture were employed to justify the protective efficacy of J gMe. In addition, the phenolic and flavonoid contents of the extract were quantified, and antioxidant activity was investigated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide, hydrogen peroxide, and hydroxyl free radical scavenging assays. Results revealed that the leaf extract caused a significant (<0.05, <0.01) decrease of the level of hepatic enzymes, triglycerides, and bilirubin and an increase of the total protein. J gMe has also significantly (<0.05, <0.01) lowered the level of malonylaldehyde. Carbofuran markedly suppressed hepatic antioxidant enzymes, however, the leaf extract significantly augmented these enzymes. The hepatoprotective effect was demonstrated by the improvement in the histo-architectural features of liver sections of CF-intoxicated rats treated with J gMe at 500 mg/kg dose. In addition, J gMe showed moderate total phenolic and total flavonoid content, whereas the IC50 values of DPPH, nitric oxide, hydrogen peroxide, and hydroxyl free radical scavenging assays were 71.31 ± 0.42, 134.82 ± 0.14, 47.69 ± 0.38, and 118.44 ± 0.30 µg/mL, respectively. In conclusion, the present study suggests the protective role of J gMe against hepatic injury induced by CF, which may be attributed to its higher antioxidant properties and thereby scientifically justifies its traditional use.

Protective Role of Syzygium Cymosum Leaf Extract Against Carbofuran-Induced Hematological and Hepatic Toxicities.

The aim of the present study was to evaluate the protective effect of Syzygium cymosum leaf methanol extract (SCL) against carbofuran (CF)-induced hepatotoxicity in Sprague-Dawley rats, along with the identification and quantification of polyphenolic composition by high-performance liquid chromatography (HPLC). Results revealed the presence of alkaloids, tannins, and flavonoids in SCL. Similarly, HPLC analysis suggests that SCL contains some known important antioxidants, such as rutin, benzoic acid, and salicylic acid that could be responsible for the hepatoprotective activity of the extract. In CF-exposed rats, significant hematological alterations along with histological changes were marked by the presence of necrosis, congestion, and inflammation. CF-intoxication also showed an increase in lipid peroxidation and decrease in cellular antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) levels in rats compared with the control group. Furthermore, coadministration of SCL significantly ameliorated the abnormalities and improved the cellular arrangement in experimental animals. SCL also reversed the alteration of hematological and biochemical parameters and brought them back to normal levels as compared to the control group. In conclusion, S. cymosum may be one of the best sources of natural antioxidant compounds that can be used in the treatment of oxidative stress and stress-related diseases and disorders.

Protective mechanism of turmeric (Curcuma longa) on carbofuran-induced hematological and hepatic toxicities in a rat model.

CONTEXT: Turmeric (Curcuma longa L. [Zingiberaceae]) is used in the treatment of a variety of conditions including pesticide-induced toxicity. OBJECTIVE: The study reports the antioxidant properties and the protective effects of turmeric against carbofuran (CF)-induced toxicity in rats. MATERIALS AND METHODS: The antioxidant potential was determined by using free radicals scavenging activity and ferric reducing antioxidant power values. Male Wistar rats were randomly divided into four groups, designated as control, turmeric (100 mg/kg/day), CF (1 mg/kg/day) and turmeric (100 mg/kg/day) + CF (1 mg/kg/day) treatments. All of the doses were administered orally for 28 consecutive days. The biological activity of the turmeric and CF was determined by using several standard biochemical methods. RESULTS: Turmeric contains high concentrations of polyphenols (8.97 ± 0.15 g GAEs), flavonoids (5.46 ± 0.29 g CEs), ascorbic acid (0.06 ± 0.00 mg AEs) and FRAP value (1972.66 ± 104.78 µM Fe2+) per 100 g of sample. Oral administration of CF caused significant changes in some of the blood indices, such as, mean corpuscular volume, corpuscular hemoglobin, white blood cell, platelet distribution width and induced severe hepatic injuries associated with oxidative stress, as observed by the significantly higher lipid peroxidation (LPO) levels when compared to control, while the activities of cellular antioxidant enzymes (including superoxide dismutase and glutathione peroxidase) were significantly suppressed in the liver tissue. DISCUSSION AND CONCLUSION: Turmeric supplementation could protect against CF-induced hematological perturbations and hepatic injuries in rats, plausibly by the up-regulation of antioxidant enzymes and inhibition of LPO to confer the protective effect.

[Combined cytotoxicity mechanism of chlorpyrifos and carbofuran pesticides in vitro].

OBJECTIVE: To evaluate the single and combined effects of chlorpyrifos( CPF) and carbofuran( CF) pesticides on cell lines cultured in vitro, and clarify the pattern of joint action. METHODS: Rat pheochromocytoma( PC12 cells) were treated with different concentrations of CPF( 0, 50, 100, 200 and 400 µmol/L) and CF( 0, 25, 50, 100 and 200 µmol/L) for 12 h separately, the combined effects of two kinds of pesticides should be studied respectively in the low dose( CPF 50 µmol/L, CF 25 µmol/L) and high dose( CPF 200 µmol/L, CF 100 µmol/L) levels. After exposure, detectingacetylcholinesterase( ACh E) activity and using fluorescent probe 2', 7'-dichlorfluorescin diacetate( DCFH-DA), thiobarbituric acid( TBA) method, xanthine oxidation, 5, 5 '-dithio-bis-2-nitrobenzoic acid( DTNB) coloration to detect the intracellular reactive oxygen species( ROS) production, lipid peroxidation production malondialdehyde( MDA), activity of antioxidant enzymes superoxide dismutase( SOD) and glutathione peroxidase( GPx), respectively. RESULTS: Compared with the control group, CPF and CF could decrease the ACh E activity, induce ROS overproduction in a dose-effect way and increase the activity of SOD, GPx( P < 0. 01), but MDA content showed no significant change. Factorial ANOVA revealed that the combined effect of CPF and CF, there was no interaction at lower dose level, but interaction existed at higher dose level( P < 0. 01). The main mode of action was synergistic effect. CONCLUSION: Chlorpyrifos, carbofuran single or combined, has cytotoxicity effect. The main combined effect between chlorpyrifos and carbofuran is synergistic effect, oxidative stress damage may be one of the mechanisms.

Protective effect of secondary plant metabolites from Ipomoea aquatica Forsk. against carbofuran induced damages.

Plausible interactions between food contaminants and natural constituents in vivo and protective effect of polyphenols present in I. aquatica against carbofuran toxicity in Charles Foster rats were evaluated. Determinations based on antioxidant enzyme activities showed significant alterations in glutathione, glutathione peroxidase, superoxide dismutase and catalase in tissues (liver and brain) and plasma of pesticide treated group while polyphenolic extracts from I. aquatica (IAE) attenuated their activities when given alongwith carbofuran. IAE decreased enhanced lipid peroxidation levels in plasma and erythrocyte membrane and cholesterol levels in brain and plasma. IAE also minimized histopathological degenerative changes produced by carbofuran. While single cell gel electrophoresis showed that secondary metabolites in leafy vegetables produced a combinatorial effect with pesticide at cellular level, DNA fragmentation level in bone marrow cells showed a decline in the IAE treated rats. Food safety adversely affected by various chemical contaminants can be retained by plant polyphenols and secondary plant constituents that can be found together in bolus. Therefore, the present study gives an insight into the protective role of naturally found polyphenols against pesticide toxicity.

Bioavailability to rats and toxicity in mice of carbofuran residues bound to faba beans.

14C-carbofuran penetrated readily into seeds of Vicia faba and the rate of penetration was found to be dose dependent. The percentage of bound residues was generally low and did not exceed 3% of the applied dose. When the bound residues were fed to rats 46% of the radioactivity was eliminated via CO2 and urine, while tissues contained 25%. Carbofuran phenol and 3-hydroxy carbofuran represented the main metabolites in the urine. These data indicate that bean-bound carbofuran residues are highly bioavailable to rats. Feeding mice with bound carbofuran residues for 90 days led to inhibition of erythrocyte cholinesterase activity after 30 days (35-40%) while the plasma enzyme remained unaffected. Serum transaminases and blood urea nitrogen were significantly elevated, indicating injury to hepatic and renal structures. The results strongly suggest that the bound residues can induce adverse biological effects in mice.