Excitation-contraction coupling, CardiomyopathyP543Histopathological findings, telomerase activity and ultrasound measurements in heart tissues after long-term rabbits exposure to propoxur and diazinon

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Abstract

Purpose

Organophospates and carbamates constitute two widely used classes of pesticides. The possible deleterious effect of diazinon (organophosphate) and propoxur (carbamate), on rabbits heart tissues is studied.

Methods

Six healthy multicoloured female rabbits of indefinable variety (weight 3200-3500 g each) were administered a high and low dose of diazinon (2.64 and 5.28 mg kg-1/day) and propoxur (8.76 and 17.52 mg kg-1/day), respectively, for 11 months. Two animals were used as controls. All rabbits before their extermination underwent a complete echocardiographic evaluation under sedation using a VIVID3 –Expert, GE system and 10 Mhz phased array cardiac ultrasound probe. For histological characterization, embedded in paraffin cardiac tissue samples, was stained with eosin – haematoxylin and examined under light microscopy. Telomerase activity in peripheral blood mononuclear cells (PBMC) and on cardiac tissues was measured using a commercial telomerase PCR-ELISA, based on the telomeric repeat amplification protocol.

Results

All pesticide-exposed animals had an average higher heart rate (171 ± 17.0) (in sedated state) compared to controls (135?10.8). Left ventricle systolic performance was generally decreasing in a dose-dependent way from controls to propoxur and diazinon-treated animals. Decrease in velocities was non-significant for propoxur and dose-dependent for diazinon, reaching a decrease of TDIs(L) 33%, TDIe(L) 45% and TDIa(L) 33% for high-dose-diazinon-treated animals, compared to controls (TDIs(L)=9?0.8 cm/s, TDIe(L)=11?0.12 cm/s and TDIa(L)=6?0.9 cm/s). Cardiac tissue in all pesticide-exposed animals was characterized by hemorrhagic impregnation and degeneration of muscle cells, with no signs of inflammation. Telomerase activity, however, remained statistically unchanged compared to controls, while telomerase activity in PBMCs non-significantly increased in a dose-dependent manner, compared to controls (relative telomerase activity in low and high-propoxur dose 137% and 227%, respectively).

Conclusions

Based on echocardiographic and histological findings, a mild localised cardiotoxic effect of diazinon and propoxur has been identified, after long-term exposure of rabbits, while systemic inflammation, as depicted by telomerase activity in PBMC, is starting to accumulate.

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