Hexane is a widely used organic solvent in industry, and chronic hexane poisoning is the main occupational toxic lesion in China. In particular, axonal and myelin lesions in the distal thick fibers of the peripheral nervous system may be caused by 2, 5-hexanedione (2, 5-HD), an intermediate metabolite of n-hexane in humans. Hexane has toxic effects not only on the nervous system but also on the liver, kidneys, and reproductive organs. In this paper, we review the progress of research on the mechanism of n-hexane toxic neuropathy.
Humans ; Hexanes/toxicity* ; Hexanones ; Industry ; Solvents

China ; epidemiology ; Hexanes ; toxicity ; Humans ; Occupational Diseases ; epidemiology ; Trichloroethylene ; toxicity

Animals ; Biomarkers ; Hexanes ; poisoning ; toxicity ; Humans ; Neurotoxicity Syndromes ; etiology

OBJECTIVETo investigate the injury in the retina of rats exposed to n-hexane.

METHODSThirty-two SD male rats were randomly divided into control group and four n-hexane groups. The rats in the four n-hexane groups inhaled 35.2 g/m3 n-hexane statically for 1, 3, 7 and 14 days respectively (6 rats in every group) while 8 rats in the control group inhaled air. Histopathology and ultrastructure changes of the retina of rats were analyzed.

RESULTSRats in control group had clear layers of retinal structure, stained evenly and with regular cell shape. Retinal degeneration was observed in the rats exposed to n-hexane for 7 d and 14 d, and aggravated by degrees with time exposed to n-hexane. In the rats exposed to n-hexane for 14 d, the outer segments of photoreceptor were arranged in a confusing order, and topically there appeared dissolution; in the inner segments, mitochondria were swollen or disappeared. Pyknotic chromatin and cytoplasmic edema were observed in the outer nuclear layer. There were degeneration of horizontal cells, bipolar cells and amacrine cells in the inner nuclear layer. Cytoplasmic edema and organelle dissolution were observed in ganglionic cells. In the neurofibromas layer, outer and inner plexiform layers, there was neuron cell tuber edema, and the microfilament and vacuole of synapse decreased.

CONCLUSIONThe histopathology and ultrastructure of retina are damaged in the rats exposed to n-hexane, thus leading to ocular fundus disease.

Animals ; Hexanes ; toxicity ; Male ; Rats ; Rats, Sprague-Dawley ; Retina ; drug effects ; pathology ; ultrastructure

OBJECTIVETo investigate the toxic effects of n-hexane on the Ganod of female mice.

METHODSn-Hexane was administered to four groups of mice by inhalation at doses of 0, 3.0, 15.1, and 75.8 mL/m3 respectivelyfor five weeks. Each group consisted of 10 mice, of which half were injected in first with 10 IU of pregnant mare serum gonadotrophin (PMSG) on the 33rd days, and then with 10 IU of human chorionic gonadotrophin (HCG) 48 hrs later. After the treatment, mouse sera were sampled and ovulating hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P4) levels were measured by electrochemiluminescence immunoassays (ECLIA). In each group, the right ovaries of the non-super-ovulated mice were stained with hematoxylin and eosin while ovaries on the left side were prepared with the TUNEL method in order to detect apoptotic cells.

RESULTSThe duration of the diestrus stage decreased significantly (P < 0.05) in the 75.8 mL/m3 group. All super-ovulated mice in each treatment group produced fewer eggs than those in the control group (P < 0.05). The number of follicles in ovaries in the 75.8 mL/m3 group was smaller compared with the control group (P < 0.05).The serum P4 levels in each treatment group were lower than those in the control group (F = 6.196, P < 0.01). The cell apoptotic rate in the 75.8 mL/m3 group was higher (P < 0.05).

CONCLUSIONn-Hexane may have directly mediated via alterations hormone secretion and promoted granulosal cell apoptotic, which may be one of the important mechanisms for n-hexane induced mouse ovary impairment.

Animals ; Female ; Gonadal Steroid Hormones ; metabolism ; Hexanes ; administration & dosage ; toxicity ; In Situ Nick-End Labeling ; Inhalation Exposure ; Mice ; Ovary ; drug effects

OBJECTIVEThis study was aimed to determine the effects of n-hexane on the maturation of mouse oocytes.

METHODSCell culture was used to observe the maturation of mouse oocytes and CLSM was employed to determine their apoptosis.

RESULTSGerminal vesicle breakdown (GVBD) and extrusion of the first polar body in mouse oocytes were significantly inhibited by n-hexane. After fertilization, the number of eggs in the mouse was significantly reduced by n-hexane. Mitochondrial membrane potentials (ΔΨm) were altered in mouse oocytes that were leading to apoptosis of the oocytes.

CONCLUSIONN-hexane might have affected the maturation of oocytes, causing alteration of ΔΨm and leading to apoptosis which maybe one of the most important mechanisms.

Animals ; Apoptosis ; drug effects ; Environmental Pollutants ; toxicity ; Female ; Fertilization ; drug effects ; Hexanes ; toxicity ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Mice ; Mice, Inbred ICR ; Oocytes ; drug effects ; growth & development

OBJECTIVETo observe the expression of Clara cell secretory protein(CCSP) in the Kunming mouse model of n-hexane long-term inhalation, and to discuss the functions of Clara cell in injury lung induced by n-hexane.

METHODS24 healthy mice were randomly divided into 4 groups: one control group and three n-hexane groups (4 w, 8 w and 12 w), 6 each group. Primary concentration of n-hexane was 17.6 g/m3, 8 hours per day, 6 d per week. After inhalation, n-hexane concentration of blood from celiac artery was detected. The lungs were embedded with paraffin and HE staining in the routine. The ratio of Clara cells with CCSP reaction in bronchiole and the number of macrophage cells with lysozyme reaction were determined by immuno-histochemistry.

RESULTSIn the poisoning groups, the average n-hexane concentration of blood was significantly higher than that of the control group (P < 0.01). There were apparent pathologic damages in lungs of the poisoning mice. In poisoning 4 w, 8 w and 12 w groups, the ratio of Clara cells was significantly decreased [(73.33 +/- 4.21)%, (60.98 +/- 4.94)%, (34.04 +/- 2.33)% in terminal bronchiole, and (75.44 +/- 7.91)%, (58.54 +/- 4.86)%, (33.35 +/- 2.67)% in respiratory bronchiole] as compared with the control mice [(80.26 +/- 6.43)% and (81.74 +/- 7.75)%, P < 0.05 or P < 0.01], meanwhile the numbers of macrophage cells were gradually increased [(21.39 +/- 7.41), (28.54 +/- 10.73), (48.97 +/- 19.55) per microscopic field at 200x] in poisoning mice than those in control mice [(7.84 +/- 3.12) per microscopic field at 200x, P < 0.05 or P < 0.01].

CONCLUSIONIn injury lungs after n-hexane inhalation, Clara cells are the target cells of n-hexane toxicity effect. Clara cells play an extensive protective role in lung inflammation.

Animals ; Epithelial Cells ; metabolism ; Hexanes ; toxicity ; Inhalation Exposure ; Lung Injury ; etiology ; metabolism ; Mice ; Mice, Inbred Strains ; Toxicity Tests, Chronic ; Uteroglobin ; metabolism

Animals ; Hexanes ; blood ; toxicity ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Lung ; drug effects ; pathology ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the role of CYP2E1 in the protective effects and mechanism of garlic oil (GO) on the peripheral nerve injuries induced by n-hexane.

METHODSFifty male Wistar rats were randomly divided into five groups (n = 10): the control, the GO (80 mg/kg) control, the n-hexane (2000 mg/kg) model, the low dose GO (40 mg/kg) plus n-hexane, and the high dose GO (80 mg/kg) plus n-hexane groups. All rats were treated by intragastric administration 6 times a week for 10 weeks. The gait scores were determined every two weeks for monitoring the peripheral neurotrosis. All rats were sacrificed in 10 weeks, the activities and expression levels of hepatic CYP2E1 and 2, 5-HD in serum were examined.

RESULTSAs compared with control group, the content and activity of hepatic CYP2E1 in GO control group reduced by 83.1% and 48.3% respectively (P < 0.01), the content and activity of hepatic CYP2E1 in model group increased by 112.5% and 72.2% respectively (P < 0.01). As compared with model group, the contents of hepatic CYP2E1 in low dose and high dose GO groups reduced by 32.9% and 39.1% respectively, the activities of hepatic CYP2E1 in low dose and high dose GO groups reduced by 27.4% and 44.5% respectively (P < 0.01); the contents of serum 2,5-HD in low dose and high dose GO groups reduced by 47.7% and 78.7% respectively (P < 0.01). The gait scores in model, low dose and high dose GO groups were significantly lower than that in control group, but the gait scores in low dose and high dose GO groups were significantly lower than that in model group (P < 0.05).

CONCLUSIONGarlic oil can effectively reduce the peripheral neurotrosis induced by n-hexane due to the decreased content and activity of hepatic CYP2E1, resulting in the reduced formation of 2, 5-HD from n-hexane.

Animals ; Cytochrome P-450 CYP2E1 ; metabolism ; Garlic ; Hexanes ; toxicity ; Liver ; drug effects ; enzymology ; Male ; Peripheral Nerves ; drug effects ; pathology ; Plant Oils ; pharmacology ; Rats ; Rats, Wistar

BACKGROUNDChronic exposure to n-hexane can lead to peripheral neuropathy that no effective treatment regimen could be applied presently. This study investigated whether myelin protein zero (P0) protein and its antibody could be used to distinguish n-hexane intoxication and protect workers from peripheral neuropathy.

METHODSWe compared P0 protein and its antibody among three levels of n-hexane-exposed groups, which included 18 patients with n-hexane-induced peripheral neuropathy as case group, 120 n-hexane-exposed workers as n-hexaneexposed control group, and 147 non-hexane-exposed participants used as control group. ELISA method was applied to detect P0 protein and its antibody.

RESULTSP0 protein in serum was significantly higher in the case group and n-hexane-exposed control group in comparison with the control group (P < 0.01). Compared with the n-hexane-exposed control group, the case group also had significant increase of P0 protein (P < 0.01). After 6 months therapy, P0 protein was observed to decrease significantly in the case group (P < 0.01). The P0 antibody in serum was significantly higher in the n-hexane-exposed control group than in the control group (P < 0.01), but not significantly different between cases and controls.

CONCLUSIONSP0 antibodies in serum may be a short-term effect biomarker for n-hexane exposure. P0 protein in serum may be an early effective biomarker for peripheral nerve neuropathy and its biological limit value needs investigation in the future study.

Adult ; Antibodies ; blood ; immunology ; Cross-Sectional Studies ; Female ; Hexanes ; toxicity ; Humans ; Male ; Myelin P0 Protein ; blood ; immunology ; Peripheral Nervous System Diseases ; blood ; chemically induced ; immunology ; Young Adult