Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg), an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05) and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05), catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05) and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05) showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05), and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05) and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05) response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05) suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05) suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally) with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

Influence of the organophosphorus insecticide phosphamidon on lentic water.

The inland freshwater resources are being increasingly subjected to heavy stress as a result of indiscriminate dumping of industrial wastes, domestic sewage and agricultural run-off causing deterioration of the water quality and adverse impact on aquatic biota. Pesticides drained to the aquatic environment are primarily of agricultural origin. Phosphamidon (widely used organophosphate pesticide in paddy field) significantly reduced dissolved oxygen (DO) at 1.8 mg/l exposure and reduced alkalinity at 0.9 and 1.8 mg/l. Hardness also reduced gradually but not significantly. Free carbondioxide was increased significantly at 1.8 mg/l of the insecticide compared to control. The insecticide had no influence on pH and temperature. There was maximum reduction of phytoplankton and zooplankton population at 1.8 mg/l of phosphamidon. Though gradual reduction of plankton community was also noticed at different lower concentrations of pesticides but in case of phytoplankton an abrupt reduction (about 50% of the control) was observed. The normal behaviour and feeding rate of air breathing teleost, Channa punctatus was also hampered. Therefore, phosphamidon even at low concentrations may create disorders in the aquatic ecosystem.

Effect of dimecron on the blood parameters of Heteropneustes fossilis.

The effects of an organophosphate insecticide. dimecron. has been studied on certain haematological parameters, viz., haemoglobin concentration, RBC number, haematocrit, O2 carrying capacity of blood, etc. of Heteropneustes fossilis following exposures to the LC50 for 24 h and 96 h and 1/10 and 1/50 parts of 96 h LC50 for 90 days. There was a significant decrease in the Hb%, RBC number, HCt% and O2 carrying capcity of blood. But, there was significant increase in the MCH and MCV values following both acute and chronic exposures. The results indicate possible induction of anaemia in the exposed fish.

Male reproductive toxicity of phosphamidon: histopathological changes in epididymis.

Phosphamidon, a neurotoxic insecticide, was tested for male reproductive toxicity with special reference to the epididymis. The insecticide was fed to Wistar strain male albino rat at 35 ppm concentration in drinking water ad libitum for 30 days. After vascular perfusion, thin slices of caput and cauda epididymidis were embedded in plastic, cut at 1 micron thickness and stained in toluidine blue for light microscopic observation. Principal cells of the caput epididymidis were vacuolarized and seen to pinch off fragments apically. In the proximal cauda the clear cells increased in height and in the size of the secondary lysosomal granules. In the distal cauda the clear cells appeared swollen out of proportion. Phosphamidon appears to affect the principal cells indirectly through its toxic effect on the Leydig cells; the clear cells of the cauda appear to be directly vulnerable to the toxic action of the pesticide.

Individual and combined toxicity of common pesticides to teleost Puntius conchonius Hamilton.

Individual and combined toxicity of three pesticides, endosulfan, phosphamidon, and aldicarb was evaluated in P. conchonius. The 48 hr LC50 was 21.36 and 446.5 ppm respectively for endosulfan and phosphamidon. When tested jointly, 48 hr LC50 for different ratios of these pesticides were 0.332 (IE:3P), 0.224 (IE:1P), and 0.178 ppm (3E:1P). The cotoxicity coefficients for these combinations were 1793, 3986, and 10009, respectively. An equitoxic mixture of endosulfan, phosphamidon, and aldicarb yielded a 48 hr LC50 of 130.5 ppm. An enhanced toxic impact is indicated when the pesticides are present together rather than as individual compounds.

Acute neurobehavioural toxicity of phosphamindon and its drug-induced alteration.

Phosphamidon, a systemic organophosphate insecticide, (1.4 mg/kg - dose 1/4th of LD50 given ip), produced several autonomic, neurological and behavioral effects in mice with peak effects being at 15 min. Similar dose in rats also abolished conditioned avoidance response. Pre-treatment with atropine, iproniazid, alpha-methyl-p-tyrosine, p-chlorophenylalanine or thiosemicarbazide reduce many of these effects. This suggests that phosphamidon toxicity involves the central cholinergic, adrenergic, serotonergic and GABAergic systems in addition to peripheral cholinergic effects.