Acute dose of lindane (40 mg/kg body weight, ip) caused significant reduction in butyrylcholinesterase (BChE) activity both in olfactory lobe and cerebrum of mice along with reduction in catalase (CAT), total protein and elevation in superoxide dismutase (SOD) and cholesterol contents. Pretreatment by a combination of antioxidants, vitamin E, vitamin C, a- lipoic acid and stilbene resveratrol (125 mg/kg body weight, ip) significantly augment the altered level of BChE and protect the other parameters in both the brain regions. The results were adequately in agreement with the histochemical findings, suggesting the neuroprotective efficacy of combination of antioxidants studied on the lindane induced neurotoxicity.

Reactive oxygen species (ROS) may be involved in the toxicity of chlorpyrifos-ethyl (CE) [O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)phosphorothioate]. We have, therefore, examined the in vivo effects of CE on the rat erythrocyte antioxidant system and evaluated the ameliorating effects of melatonin and a combination of vitamin E and vitamin C on the oxidative damage induced by CE. The experimental groups were: (1) control group, (2) CE-treated group (CE), (3) vitamin E plus vitamin C treatment group (Vit), (4) melatonin-treated group (Mel), (5) vitamin E plus vitamin C plus CE treatment group (Vit + CE), and (6) melatonin plus CE treatment group (Mel + CE). Vitamin E and vitamin C were administered intramuscularly once a day for 6 consecutive days at 150 and 200 mg/kg, respectively, in the Vit and Vit + CE groups. Melatonin was administered intramuscularly at 10 mg/kg per day for 6 consecutive days in the Mel and Mel + CE groups. At the end of the fifth day, the rats of CE, Vit + CE and Mel + CE groups were treated orally with the first of two equal doses of 41 mg/kg CE, the second oral dose being given 21 h later. Blood samples were taken 24 h after the first CE administration. Levels of thiobarbituric acid reactive substance (TBARS), antioxidant defence potential (AOP), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were determined in erythrocytes. In comparison with the control group, oral administration of CE significantly (P<0.05) stimulated TBARS activity while significantly (P<0.05) inhibiting AOP and the activities of SOD and CAT. However, GSH-Px activity remained unchanged by CE treatment. Treatment with melatonin and vitamins E plus C significantly (P<0.05) reduced the CE-induced increase of TBARS, and overcame the inhibitory effect of CE on SOD and CAT, but not on AOP. Melatonin treatment significantly (P<0.05) increased only GSH-Px activity, irrespective of the effect of CE. These results suggest that CE treatment increases in vivo lipid peroxidation and decreases antioxidant defence by increasing oxidative stress in erythrocytes of rats, and melatonin and a combination of vitamin E and vitamin C can reduce this lipoperoxidative effect.

CONTEXT: Lipophilic toxicants have been associated with hormone disruption, immune system suppression, reproductive disorders, several types of cancer, and other diseases. Due to environmental persistence and bioaccumulation, body burdens of certain toxicants, such as dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyls (PCBs), appear to be a health risk despite the toxicants' having been banned for decades. OBJECTIVE: To determine whether a safe, standardized, Ayurvedic detoxification procedure can mobilize lipid-soluble toxicants and stimulate their excretion. DESIGN: Cross-sectional and longitudinal evaluations. SETTING: Southeastern Iowa. PARTICIPANTS: In the cross-sectional study, 48 participants who had undertaken lipophil-mediated detoxification were compared with 40 control subjects. In the prospective, longitudinal evaluation, serum levels were measured in 15 subjects before and after they underwent the detoxification procedure. These 15 subjects served as their own controls. INTERVENTION(S): Ayurvedic lipophil-mediated detoxification procedure. MAIN OUTCOME MEASURE: Gas chromatographic analysis of 17 serum toxicant levels (9 PCB congeners and 8 pesticides or metabolites) on a lipid-adjusted and wet-weight basis (ng/g) as parts per billion. RESULTS: In the cross-sectional study, gas chromatographic analysis of 9 PCB congeners and 8 pesticides revealed that serum PCB levels were significantly lower in the detoxification subjects than in controls. Trans-nonachlor (TNC), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), oxychlordane, and hexachlorobenzene (HCB) levels were also markedly lower in the detoxification group. All subjects had undetectable levels of p,p'-DDT, lindane, and a-hexachlorocyclohexane (a-HCH). Beta-hexachlorocyclohexane (beta-HCH) levels were significantly higher in detoxification subjects than in controls. In the longitudinal evaluation, after treatment, mean levels of PCBs (46%) and beta-HCH (58%) declined significantly in the subjects. CONCLUSIONS: The higher beta-HCH levels in the subjects in the longitudinal study appear to be an anomaly related to diet. The results of the 2 studies generally suggest that lipophil-mediated detoxification may be effective in reducing body burdens of fat-soluble toxicants. As numerous people worldwide are at risk from high body burdens of such lipid-soluble agents, further studies to evaluate this procedure appear warranted.

Nephrotoxicity induced by chlorpyrifos-ethyl (CE) and ameliorating effects of melatonin and vitamin E plus vitamin C were evaluated in rats exposed to CE. Experimental groups were as follows: control (C), CE treated (CE), vitamin E plus vitamin C treated (Vit), melatonin treated (Mel), vitamin E plus vitamin C plus CE treated (Vit+CE), and melatonin plus CE treated (Mel+CE). The rats in the CE, Vit+CE and Mel+CE groups were administered orally with CE in two equal doses of 41 mg/kg body weight (0.25 LD50). Melatonin and vitamins E and C were administrated intramuscularly at the doses of 10, 150 and 200 mg/kg, respectively. The levels of thiobarbituric acid reactive substance (TBARS) and antioxidant potential (AOP), and the activities of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were studied in the homogenates of kidney tissue. There were no significant differences in the activities of SOD and CAT between the experimental groups. The level of TBARS increased significantly (P<0.05) while AOP decreased significantly (P<0.05) in the CE group compared with the C group. GSH-Px activity was significantly (P<0.05) lower in the CE group and higher in the melatonin group than the control group. Histopathological changes were found in the kidney tissue of rats treated with CE. These were infiltration in mononuclear cells at perivascular and peritubular areas, hydropic degenerations in tubule epithelium and glomerular sclerosis. The severity of the lesions was reduced by administration of vitamins and melatonin. These results suggest that CE increases lipid peroxidation and decreases AOP by increasing oxidative stress, and that high doses of melatonin and a combination of vitamin E plus vitamin C considerably reduce the toxic effect of CE on kidney tissue of rats.