Liver histopathological and oxidative stress assessment by a combination of formaldehyde and oxytetracycline in sea bass (Dicentrarchuslabrax L).

Background: Formaldehyde (FA) and oxytetracycline (OTC) are the chemicals commonly used in aquaculture to prevent or treat fish diseases due to protozoa, parasites, and bacteria. Aim: The goal of the present study is to assess the liver injury and oxidative stress induced by exposure of sea bass (Dicentrarchuslabrax L) to therapeutic doses of FA (200 ml.m-3) and OTC (40 g.m-3) under the same conditions being applied in intensive aquaculture systems in Tunisia. Methods: The liver histopathological survey was achieved after 5 and 10 days of exposure to FA, OTC separately or mixed. In parallel, liver catalase activity and malondialdehyde (MDA) were measured to assess oxidative stress. Results: Results showed that treatment with FA and OTC used alone or in combinations induced liver damage as measured by sinusoid dilatation, intensive vacuolization, blood congestion, and focal necrosis. Significant elevation in catalyze activity and MDA levels were also observed in liver homogenates by the treatment (p ≤ 005). Conclusion: Combined treatment induced higher effects suggesting the critical hazards associated with FA and OTC when released to the environment.

Mini-review highlighting toxic effects of triflumuron in insects and mammalian systems.

Pesticides have been used to kill pests such as insects, fungi, rodents, and unwanted plants. As these compounds are potentially toxic to the target organisms, they could also be harmful to human health and the environment. Several chronic adverse effects have been identified even after months or years of exposure. The adverse effects of pesticides on the agricultural ecosystem have been a matter of concern in recent decades. In this review, we present an overview of the studies, including our previous studies, monitoring currently used pesticides in the Tunisian agricultural soils that belong to the class of insect growth regulators (IGRs). Triflumuron (TFM) is a benzoyl phenyl urea insecticide belonging to the class of IGRs. TFM is widely used around the world to increase crop yield by protecting them from damage caused by insects. TFM works by inhibiting the synthesis of chitin, an essential part of the insect cuticle, making it susceptible to pathogens and deformities. Consequently, insects become more susceptible to pathogens and malformations. However, studies revealing its toxicity and its mode of action in mammalian systems remain very limited. The aim of this review is to better inform the community about the impact of TFM on crops, the environment, and human beings by summarizing its toxic effects.

The protective effects of thymol and carvacrol against di (2-ethylhexyl) phthalate-induced cytotoxicity in HEK-293 cells.

The protective effects of thymol and carvacrol, two phenolic monoterpenes with a wide spectrum of pharmacological effects, against the oxidative stress produced by the di (2-ethylhexyl) phthalate (DEHP) in human embryonic kidney cells 293 cells (HEK-293 cells) were investigated in this study. The cytotoxicity was monitored by cell viability, while oxidative stress generation was assessed by reactive oxygen species (ROS) quantification, antioxidant enzyme activities measurement, glutathione concentration, and malondialdehyde (MDA) quantification. The genotoxicity was evaluated by the measurement of DNA fragmentation through the Comet assay. Our results demonstrated that the pretreatment of HEK-293 cells with thymol or carvacrol, 2 h before DEHP exposure, significantly increased the cell viability, decreased the ROS overproduction, modulated catalase (CAT), and superoxide dismutase (SOD) activities, restored the reduced glutathione content, and reduced the MDA level. The DNA fragmentation was also decreased by thymol and carvacrol pretreatment. These findings suggest that thymol and carvacrol could protect HEK-293 cells from DEHP-induced oxidative stress.

Nephroprotective Efficacy of Selenium and Zinc Against Potassium Dichromate-Induced Renal Toxicity in Pregnant Wistar Albino Rats.

Hexavalent chromium (CrVI) compounds are potent toxicants commonly used in numerous industries. Thus, potential toxic effects and health hazards are of high relevance. Selenium (Se) and zinc (Zn) are known for their antioxidant and chemoprotective properties. However, little is known about their protective effects against CrVI-induced renal damage during pregnancy. In this context, the present study aimed to investigate the protective efficacy of these two essential elements against potassium dichromate-induced nephrotoxicity in pregnant Wistar Albino rats. Female rats were divided into control and four treated groups of six each receiving subcutaneously on the 3rd day of pregnancy, K2Cr2O7 (10 mg/kg, s.c. single dose) alone, or in association with Se (0.3 mg/kg, s.c. single dose), ZnCl2 (20 mg/kg, s.c. single dose) or both of them simultaneously. The nephrotoxic effects were monitored by the evaluation of plasma renal parameters, oxidative stress biomarkers, DNA damage, and renal Cr content. The obtained results showed that K2Cr2O7 disturbed renal biochemical markers, induced oxidative stress and DNA fragmentation in kidney tissues, and altered renal histoarchitecture. The co-administration of Se and/or ZnCl2 has exhibited pronounced chelative, antioxidant, and genoprotective effects against K2Cr2O7-induced renal damage and attenuated partially the histopathological alterations. These results suggest that Se and Zn can be used as efficient nephroprotective agents against K2Cr2O7-induced toxicity in pregnant Wistar Albino rats.

Protective effects of selenium and zinc against potassium dichromate-induced thyroid disruption, oxidative stress, and DNA damage in pregnant Wistar rats.

Hexavalent chromium (CrVI) is an environmental pollutant and an endocrine-disrupting metal. Se and Zn are essential trace elements, known to play a crucial role in thyroid homeostasis. However, there is a lack of data reporting thyrotoxicity during gestation. In this study, we investigated the protective effects of selenium and zinc against potassium dichromate-induced thyrotoxicity in pregnant Wistar rats. Thirty pregnant Wistar rats were divided into control and four treated groups receiving subcutaneously (s.c) on the 3rd day of pregnancy, K2Cr2O7 (10 mg/kg, s.c) alone, or in association with Se (0.3 mg/kg, s.c), ZnCl2 (20 mg/kg, s.c), or both of them simultaneously. The hormonal profile, oxidative stress biomarkers, DNA damage, and histological modifications were evaluated. Our main findings showed that K2Cr2O7 promoted hypothyroidism, oxidative stress, genotoxicity, and histological alterations in the thyroid gland. The co-treatment with Se or ZnCl2 has mitigated K2Cr2O7-induced thyrotoxicity in pregnant Wistar rats by exhibiting antioxidant and genoprotective effects. However, the combined co-treatment of both of them was less thyroprotective, and therefore, further investigations on the synergetic interaction of Se and Zn against CrVI toxicity using different doses and exposure routes are required.

Effect of di(2-ethylhexyl) phthalate on Nrf2-regulated glutathione homeostasis in mouse kidney.

Environmental toxicants such as phthalate have been involved in multiple health disorders including renal diseases. Oxidative damage is implicated in many alterations caused by phthalate especially the di(2-ethylhexyl) phthalate (DEHP), which is the most useful phthalate. However, information regarding its mechanism of renal damage is lacking. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates gene expression implicated in free radical scavenging and cytoprotection including the antioxidant glutathione (GSH) pathway. The aim of this study was to assess whether DEHP affects the Nrf2 pathway and the GSH concentration. Mice were divided into four groups: a control group and three groups treated with DEHP at different concentrations (5, 50, and 200 mg/kg body weight) for 30 days. Our results showed that DEHP altered the normal levels of serum biochemical parameters creatinine (CREA), urea, and lactate dehydrogenase (LDH). This phthalate caused oxidative damage through the induction of lipid peroxidation and protein oxidation as marked by increase of protein carbonyl (PC) and loss of protein-bound sulfhydryls (PSH). Simultaneously, DEHP treatment decreased the protein level of Nrf-2, HO-1, and GCLC (responsible of GSH synthesis) and decreased the GSH level. Inhibition of the Nrf2 pathway is related to the activation of the mitochondrial pathway of apoptosis. This apoptotic process is evidenced by an upregulation of p53 and Bax protein levels in addition to a downregulation of Bcl-2. Collectively, our data demonstrated that depletion of Nrf2 and GSH was associated with the elevation of oxidative stress and the activation of intrinsic apoptosis in mouse kidney treated with DEHP.

Triflumuron induces cytotoxic effects on hepatic and renal human cell lines.

Insect growth regulator insecticides are a new class of pesticides, commonly used around the world to control insect damages. Among those compounds, we focused our interest on triflumuron (TFM), which is less toxic than other conventional insecticides. However, not much is known about its toxic effects on mammalian systems. Therefore, our study aimed toward evaluating the cytotoxic and genotoxic effects of TFM using two different cell lines, the human renal embryonic cells (HEK 293) and hepatocytes (Hep G2). We showed, according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, that TFM reduced significantly the cell viability and increased the reactive oxygen species generation, malondialdehyde levels, and mitochondrial membrane potential in both cell lines. The antioxidant system was disturbed as assessed by the increased activities in both catalase and superoxide dismutase. We demonstrated also, that TFM is an inductor of DNA damages quantified by the comet assay. Moreover, we showed an overexpression of proapoptotic Bax and a decrease in antiapoptotic Bcl-2 expression. As a conclusion, we demonstrate that the liver presents the major target organ to TFM, in which the cytotoxicity and the genotoxic effects were significantly higher in hepatic cells than in renal cells and by consequence its uses must be controlled.

Triflumuron induces genotoxicity in both mice bone marrow cells and human Colon cancer cell line.

Triflumuron (TFM) is an insect growth regulator (IGR), an insecticide commonly used over the world. It is known for its several toxic manifestations, such as reprotoxicity, immunotoxicity and hematotoxicity, which could affect public health. However, studies that reveal its toxic effects on mammalians are limited. To reach this purpose, our study aimed to elucidate the eventual genotoxic effects of TFM in mice bone marrow cells and in HCT 116 cells after a short term exposition. TFM was administered intraperitoneally to Balb/C male mice at doses of 250, 350 and 500 mg/kg bw for 24 h. Genotoxicity was monitored in bone marrow cells using the comet test, the micronucleus test and the chromosome aberration assay. Our results showed that TFM induced DNA damages in a dose-dependent manner. This genotoxicity was confirmed also in vitro on human intestinal cells HCT 116 using the comet test. It was then asked whether this genotoxicity induced by TFM could be due to an oxidative stress. Thus, we found that TFM significantly decreased HCT 116 cell viability. In addition, it induced the generation of reactive oxygen species (ROS) followed by lipid peroxidation as revealed by the increase in the malondialdehyde (MDA) levels. Similarly, the activation of the antioxidant enzymes (catalase and superoxide dismutase) was also observed. Our results indicated that, in our experimental conditions, TFM had a genotoxic effect on bone morrow cells and in HCT 116 cells. Moreover, we demonstrated that this genotoxicity passes through an oxidative stress.

Protective effect assessment of Moringa oleifera against cadmium-induced toxicity in HCT116 and HEK293 cell lines.

The cadmium (Cd) is considered one of the widespread toxic metals in the aquatic and terrestrial environments, which is due to its long half-life, non-degradable characteristic, and toxicity. Aqueous extract of freeze-dried Moringa oleifera (Moringaceae family) leaves was examined for protective effect and antioxidant power against Cd toxicity. The results revealed that Moringa aqueous extract (MAE) has contents of total polyphenols and flavonoids about 30.14 mg GAE/g and 18.35 mg QE/g respectively. Furthermore, phenolic compounds in leaves of Moringa were studied using a high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS). Results showed that the largest number of phenolic compounds determined in leaves of Moringa belongs to flavonoids. Moreover, biological properties were determined by radical scavenging capacity (DPPH) and ferric-reducing power (FRAP). Cytoprotective effect and antioxidant power of Moringa extract were assessed using the mitochondrial activity testing method (MTT test), malondialdehyde (MDA), and reactive oxygen species (ROS) production. Results indicate that Moringa aqueous extract have a significant (i) proliferative, (ii) antioxidant, and (iii) cytoprotective effect on HCT116 and HEK293 cells against metal toxicity.

Protective effects of fennel essential oil against oxidative stress and genotoxicity induced by the insecticide triflumuron in human colon carcinoma cells.

The increased use of pesticides is the origin of multiple damages to the environment and to humans; thus, the search for new strategies to reduce or even protect the toxic effects caused by these synthetic products became a necessity. In this context, our study attempted to evaluate the protective effects of fennel essential oil (FEO), the main essential oil extracted from Faeniculum vulgare Mill., a plant with aromatic, flavorful, and medicinal uses, against toxicity induced by an insecticide-triflumuron (TFM)-in human carcinoma cells (HCT116). Our methodological approach consists of the cytotoxicity assay starting with the cell viability test, the ROS generation, the malondialdehyde (MDA) production, the DNA fragmentation, and the measurement of some antioxidant enzymes activities such as catalase (CAT) and superoxide dismutase (SOD). Also, we measured the mitochondrial transmembrane potential. The outcome of the current study showed clearly that after 2 h of HCT 116 cell pretreatment with FEO, there were increase in cell viability, reduction in ROS generation, and modulation in CAT and SOD activities induced by TFM. In the same manner, significant decreases in MDA levels were found. Mainly, the results indicated a perceptible decrease in DNA damages and a significant reduction in the mitochondrial membrane potential loss. Our work demonstrates that FEO can be an important protector against toxic effects induced by TFM in HCT 116 cells.

Di (2-ethylhexyl) phthalate targets the thioredoxin system and the oxidative branch of the pentose phosphate pathway in liver of Balb/c mice.

Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that gives flexibility to various polyvinyl chloride products. It is a pollutant easily released into the environment and can cause many adverse effects to living organisms including hepatotoxicity. The thioredoxin system is a determining factor in the redox balance maintaining in the liver, which is a vulnerable tissue of reactive oxygen species overproduction because of its high energy needs. In order to determine if the thioredoxin system is a target in the development of DEHP hepatotoxicity, Balb/c mice were administered with DEHP intraperitoneally daily for 30 days. Results demonstrated that after DEHP exposure, biochemical profile changes were observed. This phthalate causes oxidative damage through the induction of lipid peroxydation as well as the increase of superoxide dismutase and catalase activities. As new evidence provided in this study, we demonstrated that the DEHP affected the thioredoxin system by altering the expression and the activity of thioredoxin (Trx) and thioredoxin Reductase (TrxR1). The two enzyme activities of the oxidative phase of the pentose phosphate pathway: Glucose-6-phosphate dehydrogenase and 6-Phosphogluconate dehydrogenase were also affected by this phthalate. This leads to a decrease in the level of nicotinamide adenine dinucleotide phosphate used by the TrxR1 to maintain the regeneration of the reduced Trx. We also demonstrated that such effects can be responsible of DEHP-induced DNA damage.

Di(2-ethylhexyl) phthalate inhibits glutathione regeneration and dehydrogenases of the pentose phosphate pathway on human colon carcinoma cells.

Phthalates, particularly di(2-ethylhexyl) phthalate (DEHP), are compounds widely used as plasticizers and have become serious global contaminants. Because of the bioaccumulation of such substances, the food chain is at risk. The food contamination by some phthalates has been linked to different side effects in experimental animals. That is why we have chosen the intestinal system's cells which represent the primary targets of these compounds to test their toxic effects. Human colon carcinoma cells (HCT 116) were chosen to elucidate whether DEHP triggers oxidative stress and apoptosis. Our results indicated that DEHP is cytotoxic; it induces the overexpression of Hsp70 protein and causes oxidative damage through the generation of free radicals leading to lipid peroxidation induction and the increase of superoxide dismutase (SOD) and catalase (CAT) activities. In addition, cell treatment with DEHP resulted in a glutathione (GSH) content decrease and a decrease in the glutathione reductase (GR) activity. As new evidence provided in this study, we demonstrated that the DEHP affected the two enzymes' activities of the oxidative phase of the pentose phosphate pathway: Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD). This leads to a decrease in the level of NADPH used by the GR to maintain the regeneration of the reduced GSH. We also demonstrated that such effects can be responsible for DEHP-induced apoptosis.

Partial characterization of the edible Spinacia oleracea polysaccharides: Cytoprotective and antioxidant potentials against Cd induced toxicity in HCT116 and HEK293 cells.

Spinacia is an interesting medicinal halophyte plant that is employed as a food and therapeutic agent in traditional medicine. In this work, water-soluble polysaccharides from Spinacia oleracea were extracted and preliminary characterization was established via FT-IR, UV-vis, 1H NMR and SEC/MALS DRI technics. The extracted polysaccharide, with an average molecular mass of 408 kDa, was composed of arabinose, galactose, mannose, glucose, rhamnose and xylose in the molar percentage of 49.3%, 28.1%, 4.9%, 7.8%, 8.2% and 1.7%, respectively. The polysaccharide showed significant antioxidant activity. Moreover, Spinacia polysaccharide, significantly prevented oxidation-induced Cd damage and exhibited a protective effect against Cd cytotoxicity on HEK293 and HCT116 cells, with an important cell viability decrease, an important reduction of MDA production and ROS levels. The outcomes obtained suggest that the Spinacia polysaccharides may be used as an accessible source of natural antioxidants and as potential phytochemicals against kidney and colon cancer.

Di (2-ethylhexyl) phthalate induces cytotoxicity in HEK-293 cell line, implication of the Nrf-2/HO-1 antioxidant pathway.

The di (2-ethylhexyl) phthalate (DEHP) is a plasticizer used in the polyvinyl chloride industry. Human exposure to this plasticizer is inevitable and contributes to several side effects. In this study, we examined whether DEHP induces apoptosis and oxidative stress in embryonic kidney cells (HEK-293) and whether the nuclear factor E2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1) antioxidant pathway is involved in the pathogenesis of this process. We demonstrated that DEHP is cytotoxic to HEK-293 cells. It causes oxidative damage through the generation of free radicals, induces lipid peroxidation, and alters superoxide dismutase and catalase activities. Simultaneously, DEHP treatment decreases the expression and the protein level of Nrf-2 and HO-1. Inhibition of the Nrf-2/HO-1 pathway is related to the mitochondrial pathway of apoptosis. This apoptotic process is characterized by a loss of mitochondrial transmembrane potential (ΔΨm) and upregulation of the expression of caspase-3 mRNA as well as its protein level.

Metabolism of triflumuron in the human liver: Contribution of cytochrome P450 isoforms and esterases.

Triflumuron (TFM) is a benzoylurea insecticide commonly used in Tunisian agriculture and around the world to control crop pests and flies as a promising alternative to conventional insecticides for its arthropod specificity and low toxicity. From the evidence available in animal models, it can be expected that the metabolism of TFM is catalyzed by cytochrome P450 (CYP) and esterases. However, no data are available on human metabolism of TFM with regards to phase I metabolism and CYP isoform specificity. Hence, this manuscript describes experimental investigations to underpin in vitro phase I TFM metabolism in human samples for the first time. TFM biotransformation by recombinant human CYPs was characterized, then human liver microsomes (HLM) and chemical specific inhibitors have been used to identify the relative contribution of CYPs and esterases. Our results showed that all CYP isoforms were able to metabolize TFM with different affinity and efficiency. The relative contribution based both on the kinetic parameters and the CYP hepatic content was 3A4 > >2C9 > 2C8 > 2A6 > 1A2 > 2B6 > 2D6 > 2C19 > 2C18 > 1A1 at low TFM concentration, whilst at high TFM concentration it was 1A2 > >2C9 = 3A4 = 2A6 > 2C19 > 2B6 = 2C8 > 2D6 > 1A1 > 2C18. Experiments with HLMs confirmed the involvement of the most relevant CYPs in the presence of specific chemical inhibitors with a catalytic efficiency (Cliapp) lower by an order of magnitude compared with recombinant enzymes. Esterases were also relevant to the overall TFM kinetics and metabolism, with catalytic efficiency higher than that of CYPs. It is foreseen that such isoform-specific information in humans will further support in silico models for the refinement of the human risk assessment of single pesticides or mixtures.

Protective effects of kefir against deltamethrin-induced hepatotoxicity in rats.

Deltamethrine (DLM) is a synthetic pyrethroid with broad spectrum activities against acaricides and insects. Widely used for agricultural and veterinary purposes, its human and animal exposure occurs by ingestion of contaminated water and food and leads to serious health problems. Kefir is fermented milk with numerous health favors counting restorative properties of bacterial flora, immune system stimulation, cholesterol reduction, as well as anti-mutagenic and anti-tumor properties. The present study was undertaken to examine the hepatoprotective and antioxidant potential of kefir against DLM toxicity in male Wistar albino rats. DLM-treated animals revealed a significant increase in serum biochemical parameters as well as hepatic protein and lipid oxidations but caused an inhibition in antioxidant enzymes. Additionally, we have observed an increase in hepatocyte DNA damages. This toxic effect was confirmed by histological study. Kefir administration normalized the elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T bilirubin), and cholesterol. It also reduced DLM-induced protein carbonyl (PC) and malondialdehyde (MDA) formations. Furthermore, Kefir treatment restored catalase (CAT) and superoxide dismutase (SOD) activities. The co-treatment as well as the pre-treatment by kefir showed an improvement of oxidative status as well as suppressed inflammation and DNA damages. However, the pre-treatment seems to be the most efficient. Therefore, it could be concluded that kefir is a natural product able to protect against the hepatotoxic effects of DLM by its free radical-scavenging and potent antioxidant activity.

Di (2-ethylhexyl) phthalate induces cardiac disorders in BALB/c mice.

Because of the extensive use of phthalates for domestic, medical, and industrial applications, the evaluation of their toxic effects is of major concern to public health. The aim of the present study was to assess the propensity of di (2-ethylhexyl) phthalate (DEHP), one of the most used phthalates, to cause oxidative cardiac damage in mice. DEHP was administered intraperitoneally at doses of 5, 50, and 200 mg/kg body weight for 30 consecutive days in BALB/c mice. We assessed the effect of DEHP on cardiac injury using biochemical profile (such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), total cholesterol (T-CHOL), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)), parameters related to myocardiac oxidative stress, such as malondialdehyde (MDA) level, protein carbonyl (PC) concentration, and DNA fragmentation. In addition, we evaluated antioxidant status; enzymatic (catalase (CAT) and superoxide dismutase (SOD) activities) and non-enzymatic (protein-bound sulfhydryl concentration (PSH)) antioxidants. Acetylcholinesterase (AChE) activity and histopathological changes were also assessed in heart mice treated with DEHP. Our results showed that DEHP induced an elevation of serum marker enzymes and perturbated the lipid profile. In addition, this phthalate increased lipid peroxidation, protein carbonyl levels, and DNA fragmentation in the heart in a dose-dependent manner. Antioxidant status was also perturbated by the increase of the CAT and SOD activities and the decrease of the protein-bound sulfhydryl concentration. AChE activity was also inhibited in the heart following the treatment with DEHP. These biochemical alterations were also confirmed by histopathological changes. Increased free radical production at various doses of DEHP would result in impairment of the redox status leading to an enhanced dose-dependent cardiotoxicity.

Acute triflumuron exposure induces oxidative stress responses in liver and kidney of Balb/C mice.

Triflumuron (TFM) is one of the most widely used insecticides over the world. It is a benzoylphenyl urea that belongs to the class of insect growth regulators. This insecticide acts by inhibiting insect's chitin synthesis and by consequences, making insect more susceptible to pathogens and malformations. TFM effects have been reported in mammalians and crops. However, studies that reveal its toxicity mechanisms are limited. In this line, the current study aimed to determine the implication of oxidative stress in the toxicity induced by TFM and particularly in the perturbation of biochemical parameters in male Balb/C mice. Male Balb/C mice were divided into three groups receiving TFM at doses of 250, 350, and 500 mg/kg bw respectively. The occurrence of oxidative stress in both kidney and liver tissues was monitored by measuring of oxidative stress markers. TFM caused an increase as protein carbonyls generation, malondialdehyde induction (MDA) and catalase (CAT), superoxide dismutase (SOD), glutathion peroxidase (Gpx), as well as glutathion S transferase (GST) activities. In the same conditions, we have evaluated the effect of TFM treatment on biochemical parameters. In response to the three TFM doses, we showed significant dose dependent inductions in all tested oxidative stress markers. However, TFM caused an increase in the liver enzyme activities as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), g-glutamyltranspeptidase (GTT), and total bilirubin (BILT) in a dose-dependent manner. Equally, renal markers as urea, uric acid, albumin, and creatinine were increased in the same manner. We can conclude that oxidative damage seems to be a key determinant of TFM-induced toxicity in both liver and kidney of male Balb/C mice. Moreover, the oxidative stress is more pronounced in the liver than in the kidney. Thus, TFM may be considered as a hepatotoxic insecticide.

Protective effects of kefir against zearalenone toxicity mediated by oxidative stress in cultured HCT-116 cells.

Kefir is a fermented milk with numerous health favors counting restorative properties of bacterial flora, reduction of the symptoms of lactose intolerance, immune system stimulation, cholesterol reduction, as well as anti-mutagenic and anti-tumor properties. Zearalenone (ZEN) is a mycotoxin produced by some Fusarium species. ZEN often occurs as a contaminant in cereal grains and animal feeds. Human exposure occurs by ingestion of mycotoxin-contaminated products and can cause serious health problems. This study aimed to assess the preventive effect of kefir against ZEN toxicity in cultured HCT-116 colorectal carcinoma cells; by the evaluation of cell viability, oxidative stress status and the initiation of apoptotic cell death pathway. Our results demonstrated that ZEN inhibits cell proliferation which was accompanied by an increase in the generation of free radicals as measured by fluorescent 2,7-dichlorofluorescein (DCF) and Malondialdehyde (MDA). As an adaptive response to this redox status, we showed an induction of heat shock protein expression (Hsp 70) and an activation of antioxidant enzymes; catalase and Superoxide Dismutase (SOD). Moreover, a loss of mitochondrial membrane potential (Δѱm) was observed. The co-treatment as well as the pre-treatment by kefir showed a reduction of ZEN induced damages for all tested markers. However, the pre-treatment seems to be the most efficient, it prevented almost all ZEN hazards. Consequently, oxidative damage appears to be a key determinant of ZEN induced toxicity in cultured HCT-116 cells. In conclusion, we showed that kefir may better exert its virtue on preventive mode rather than on curative one. By this way, kefir as a beverage with highly antioxidant properties could be relevant particularly with the emergent demand for natural products which may counteract the detrimental effects of oxidative stress and therefore prevent multiple human diseases.

Beneficial effects of mycophenolate mofetil on cardiotoxicity induced by tacrolimus in wistar rats.

The immunosuppressive drug tacrolimus (TAC) is used clinically to reduce the rejection rate in transplant patients. TAC has contributed to an increased prevalence of cardiovascular disease in patients receiving solid organ transplantation. Mycophenolate mofetil (MMF), a potent inhibitor of de novo purine synthesis, is known to prevent ongoing rejection in combination with TAC. In the present study, we investigated the antioxidant and antigenotoxic effect of MMF on TAC-induced cardiotoxicity in rats. Oral administration of TAC at 2.4, 24, and 60 mg/kg b.w. corresponding, respectively, to 1, 10, and 25% of LD50 for 24 h caused cardiac toxicity in a dose-dependant manner. TAC increased significantly DNA damage level in hearts of treated rats. Furthermore, it increased malondialdehyde (MDA) and protein carbonyl (PC) levels and decreased catalase (CAT) and superoxide dismutase (SOD) activities. The oral administration of MMF at 50 mg/kg b.w. simultaneously with TAC at 60 mg/kg b.w. proved a significant cardiac protection by decreasing DNA damage, MDA, and PC levels, and by increasing the antioxidant activities of CAT and SOD. Thus, our study showed, for the first time, the protective effect of MMF against cardiac toxicity induced by TAC. This protective effect was mediated via an antioxidant process.