Journal of Toxicology最新文献

Background: Local Ethiopians regularly use Cymbopogon martini for cosmetic purposes. The plant's safety, however, is not supported by any solid facts. This investigation aimed to evaluate the acute and subacute toxicities of C. martini essential oil in mice.

Methods: The essential oil was analyzed using GC-MS. The approach outlined by Chinedu et al., 2013 has been used to calculate the median lethal dose. According to organization for economic cooperation and development (OECD) 407 standard, a 28-day repeated dose oral toxicity study was carried out on female mice. Three groups of ten experimental mice each were distributed at random. Group I received the same saline volume and was considered the control. Groups II and III were treated with doses of C. martini of 500 mg/kg and 1000 mg/kg, respectively, of body weight. Hematological and biochemical markers were assessed. The liver and kidney were taken out after the sacrifice using sodium pentobarbital for pathological analysis.

Results: Geraniol (40.89%) was the predominant component in the essential oil composition of C. martini with cyclofenchene (13.91%), myrcene (9.34%), 2, 4, 6, octatriene, 2, 6, dimethyl (8.20%), and ocimene (5.93%) being present in small amounts. The LD₅₀ of C. martini essential oil was discovered to be greater than 5000 mg/kg body weight. During a 4-week follow-up period, mice treated with C. martini, the essential oil, at doses of 500 mg/kg or 1000 mg/kg body weight showed no evidence of toxicity or mortality. Biochemical and hematological parameters were not significantly altered in mice treated with the essential oil of C. martini compared with the control group. Histopathological evaluation of the liver and kidney did not exhibit any adverse results.

Conclusions: The essential oil of C. martini from Ethiopia is considered relatively safe and nontoxic.

Paracetamol (AKA acetaminophen) is a widely used drug and is used for mild to moderate pains, such as mild osteoarthritis, toothache, headache, and pain caused by minimally invasive surgeries. Despite being a harmless drug in lower doses, acetaminophen can be toxic to the liver and kidneys if overdosed and even results in death. In this study, the therapeutic effects of Solidago canadensis L. extract (SCE) were investigated. 48 adult male Swiss albino mice (20-30 grams) were randomly divided into six groups of 8. The control group was gavaged with normal saline every 12 hours for 6 days. The second group received paracetamol at a 500 mg/kg intraperitoneally (i.p) dose on the sixth day. The third, fourth, and fifth groups were gavaged doses of 125, 250, and 500 mg/kg of SCE every 12 hours for six days, respectively, and on the sixth day, we received paracetamol at a dose of 500 mg/kg i.p. The sixth group only received SCE every 12 hours at a dose of 1000 mg/kg via gavaging for six days. On the seventh day (24 hours after paracetamol injection), blood samples were collected to measure the serum level of creatinine, uric acid, blood urea nitrogen (BUN), total protein, albumin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total and direct bilirubin, and liver and kidney tissues were also sampled for histopathological examination. It was observed that paracetamol caused a considerable increase in the ALT, AST, ALP, uric Acid, and BUN levels (P < 0.01), while those in SCE-treated groups were significantly lower. In addition, various lesions in the paracetamol group were observed, while in the SCE-receiving groups, receiving prophylactic SCE inhibited the high-intense lesions such as the infiltration of inflammatory cells, hyperemia, and vacuolar degeneration, which decreased significantly in the control group in comparison with that of the paracetamol group (P < 0.05). In conclusion, SCE can have substantial protective effects against paracetamol's hepatorenal toxicity.

Momordica cochinchinensis or gac fruit has been reported to have several biological activities, including antioxidation, anti-inflammatory, and anticancer activities. However, the effect on cancer cell metastasis has not been extensively studied. With this aim, the extract from the aril part was selected and investigated for prostate cancer cell migration. The aril extracts were prepared as boiled extract, sonicated extract, ethanol extract, and HAE (hexane:acetone:ethanol; 2 : 1 : 1) extract, while the prostate cancer cell models were PC-3 and LNCaP cells. An MTT assay was performed to compare the antiproliferative effect between prostate cancer cells and normal Vero cells. As a result, the sonicated extract had the highest efficiency in PC-3 cells, with IC₅₀ values of 2 mg/mL and 0.59 mg/mL for 48 and 72 h, respectively, while it had less of an effect in LNCaP cells and was not toxic to normal cells. Cell damage was further confirmed using LDH and cell cycle analysis. As a result, the sonicated extract did not cause cell damage or death and only inhibited cell proliferation. The effect on cancer metastasis was further examined by wound healing, transwell migration assays, and western blotting. The results demonstrated that the sonicated extract inhibited PC-3 cell migration and decreased MMP-9 but increased TIMP-1 expression. All these results support that gac fruit is a valuable source for further development as an anticancer agent for prostate cancer patients.

Bidens pilosa (B. pilosa) and Cymbopogon citratus (C. citratus) are plants used individually or in combination in the traditional treatment of several ailments such as cardiovascular disorders. In order to valorise their traditional use, a toxicological study was conducted on the aqueous extract of the mixture of aerial parts of B. pilosa and C. citratus. The acute and subchronic toxicity studies were conducted according to the OECD 425 and 407 guidelines. Regarding the acute study, the aqueous extract of the mixture of B. pilosa and C. citratus 50 : 50 (2000 and 5000 mg/kg) was administered once to rats of both sexes. In the subchronic study, the aqueous extract of the mixture of B. pilosa and C. citratus (200, 400 and 800 mg/kg) was administered once daily to rats for 28 days. The aqueous extract of the mixture of B. pilosa and C. citratus (2000 and 5000 mg/kg) did not cause death and did not induce any apparent sign of toxicity during the 14 days of observation. The DL₅₀ of the extract is therefore greater than 5000 mg/kg. Taken daily for 28 days, the extract had no significant effect on selected parameters (creatinine, AST, ALT, urea, and uric acid) of renal and hepatic function, as well as on the number of some blood cells. However, the aqueous extract of the mixture of B. pilosa and C. citratus (200 and 400 mg/kg) caused a significant (p  <  0.05; p  <  0.001, respectively) decrease in creatinine levels in male rats as compared to normal control animals. In females, the aqueous extract of the mixture of B. pilosa and C. citratus (200 and 400 mg/kg) resulted in a significant (p  <  0.05) increase in total cholesterol levels as compared to normal control animals. The study showed that the aqueous extract of the mixture of B. pilosa and C. citratus has a low toxicity and does not cause any injury to the liver, kidney, lungs, or spleen.

Background: Chronic exposure to arsenic is a major health concern consequent upon generation of excessive reactive oxygen species. The safety of treatment with chelating agents has not been well established; therefore, there is a need for a paradigm shift in the approach to management of arsenic toxicity. Bioflavonoids are known to influence redox homeostasis in cells; the study therefore investigates the efficacy of quercetin and its zinc and iron metal complexes on sodium arsenite (NaAr)-intoxication in rats.

Methods: Spectroscopic study of quercetin hydrate and its metal complexes was performed using UV-Vis and FT-IR spectrometer. Furthermore, twenty male Wistar rats were obtained and equally divided into four groups, treated orally and daily for 28 days with 10 mg/kg NaAr, 30 mg/kg quercetin, quercetin-zinc, and quercetin-iron separately. Five more rats were used as control. Plasmatic aspartate transferase (AST), alanine transferase (ALT), creatinine (CREA), and total protein (TP) were estimated. Levels of kidney and liver lipid peroxidation (LPO), glutathione (GSH), catalase (CAT), and glutathione-S-transferase (GST) were determined. Histology was used to view the lesions.

Results: Treatment of arsenic-toxicity with quercetin and its complexes decreased the activities of ALT, AST, CREA, TP, CAT, and GST and concentration of LPO and GSH. Quercetin-zn treatment showed a better result than quercetin-iron in the liver. Histology results showed absence of lesions in quercetin zinc and iron treatment in both the kidney and the liver.

Conclusion: Quercetin zinc and iron increased the bioavailability of quercetin and therefore could be relevant as adjuvants in arsenic poisoning.

Background: Alcoholism is known to cause liver toxicity and is extensively researched. On the other hand, stress, depression, and obesity are interrelated conditions with alcoholism, and their medications would affect the liver itself. In this study, we investigated the effects of the drugs fluoxetine and atorvastatin on the liver and compared with those of alcohol in a mouse model.

Methods: Comparisons of animals treated with the three drugs were carried out: serum aspartate transaminase (AST), alanine transaminase (ALT), and albumin were measured; liver tumor necrosis factor alpha (TNF alpha) and transforming growth factor beta (TGF beta-1) levels were evaluated; proliferative cells were detected via immunohistochemistry (IHC) targeting on proliferating cell nuclear antigen (PCNA) and minichromosome maintenance complex component 2 (MCM2); for apoptosis, IHC targeting on activated caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were employed; and histopathology was also documented in all groups.

Results: For ALT, AST, albumin, and liver TNF alpha, only the ethanol group surged to significantly higher levels. For TGF beta-1, both ethanol and atorvastatin groups reached a significantly higher level. PCNA and MCM2 showed increased proliferation in the livers of all three groups, with the ethanol group having the highest number of positive cells followed by atorvastatin and then the fluoxetine group. As for cell death, both ethanol and fluoxetine groups showed significantly more apoptosis than control in TUNEL and activated caspase-3, while in the atorvastatin group, activated caspase-3 positive cells increased significantly, but the increase in TUNEL-positive cells did not reach statistical significance.

An experiment was conducted to assess malathion-induced hematological responses of Barbonymus gonionotus (silver barb) and its recovery patterns in malathion-free water. Fish (45 days old) were exposed to two sublethal concentrations, namely, 25% and 50% (i.e., 3.78 and 7.56 ppm) of LC₅₀ (15.13 ppm) of malathion for 28 days, followed by a postexposure recovery period for the same time. The hematological parameters were examined after 1, 7, 14, 21, and 28 days of exposure as well as after the postexposure recovery time. Except in the case of the control group (0% of malathion), the obtained results revealed that malathion exposure resulted in significantly (p < 0.05) higher prevalence and severity of micronucleus and lower values of Hb, PCV, and RBC and significantly higher values of WBC in a concentration- and time-dependent manner. The values of blood glucose, MCV, MCH, and MCHC showed mixed trends during the experiment. During the recovery period, all blood parameters (micronucleus, glucose, Hb, PCV, RBC, WBC, MCV, MCH, and MCHC) partially recovered, which means that the recovery period was not long enough for the organisms to recover from the previous exposure. The study thus confirms that hematology is a sensitive indicator for fish to detect toxicity caused by different chemicals. Changes in these parameters can provide useful information about environmental conditions and risk assessment of aquatic organisms.

Neonicotinoids are pesticides that act as agonists of nicotinic receptors for acetylcholine in insects' central nervous system (CNS). Chronic exposure to neonicotinoids in humans is related to autism, memory loss, and finger tremor. In this article, we evaluate the effect of subchronic oral administration of two neonicotinoids in the same mixture: clothianidin and thiacloprid. Decreasing doses of both pesticides were administered to rats starting from the lethal dose 50 (LD₅₀) reported by the manufacturer. Our results indicate that the administration of three doses of decreasing amounts of LD₅₀ (5/10, 4/10, and 3/10 LD₅₀) resulted in 100% death in all cases. Ten administration times of 2/10 LD₅₀ of the mixture caused only 20% of death cases after twenty-seven days, which was determined as a subchronic administration scheme. The animals administered 2/10 LD₅₀ showed behavioral alterations after the first and second administration. Electrographic studies showed abnormal discharge patterns in the CNS. 72 h after the tenth dose, learning and memory tests were performed in the Morris water maze. Our results revealed significant decreases in permanence at the quadrant and the number of crosses (P=0.0447,  P=0.0193, respectively), which represent alterations in the short-term memory test, but there were no significant changes in a long-term memory test. Likewise, the brains of these animals showed tissue architecture loss, nucleosomal retraction, and a significant increase in the pycnosis of the granular neurons of the dentate gyrus analyzed at 72 h after the last dose (P=0.0125). Toxic effects and cognitive deterioration that have been found in communities living near contaminated areas are probably related to the agricultural use of neonicotinoids.

Background: Belonging to the family of Combretaceae, the roots of Anogeissus leiocarpus are traditionally used to treat diabetes, wounds, infections, pain, and gastrointestinal diseases. To our knowledge, no genotoxicity assessment of the plant was reported. Hence, this study was designed to evaluate the potential genotoxic and protective effects of extract of Anogeissus leiocarpus roots using the micronucleus test on mice bone marrow cells in vivo.

Methods: Three different concentrations (250, 500, and 1000 mg·kg^-1) of hydroalcoholic extract of roots of A. leiocarpus were administered daily for 7 days per os to mice, and the genotoxicity was induced by the administration ip of cyclophosphamide. Genotoxicity and cytotoxicity were evaluated by counting, respectively, the number of micronucleated polychromatic erythrocytes and polychromatic erythrocytes to total erythrocytes in the bone marrow of mice.

Results: The administration of A. leiocarpus did neither increase the ratio of the polychromatic erythrocyte (PCE) nor the frequency of micronucleated PCE (MNPCE) significantly in the bone marrow cells of the mice, compared to the vehicle control animals. However, a significant increase in the incidence of MNPCE in the bone marrow cell of the cyclophosphamide-treated mice was found. Moreover, in the groups treated with the total extract of A. leiocarpus at different doses plus cyclophosphamide, there was a significant decrease (p < 0.0001) in MNPCEs compared to the positive controls, in a dose-dependent manner.

Conclusion: This first finding reports that the extract of A. leiocarpus was neither genotoxic nor cytotoxic. However, it shows a protective effect against the genotoxicity and cytotoxicity induced by cyclophosphamide.

Backgrounds: Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy.

Methods: Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation.

Results: Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly (P < 0.05) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% (P < 0.05). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings.

Conclusion: Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.