Abstract

Objective(s): Methylenedioxymethamphetamine (MDMA) is a hallucinogenic drug of abuse which is the most popular drugs in the world and has been shown to induce apoptosis in kidney cells. As Pentoxifylline (PTX) increases cAMP and reduces tumor necrosis factor-α, the present study aimed to investigate the effects of pentoxifylline on kidney damage induced by acute administration of MDMA in male rat.
 Materials & methods: Thirty male rats (250-300 g) were randomly divided into five groups: including control (without any intervention), MDMA group ,the group received 7.5 mg/kg MDMA three times at every two hours for one day ,first experimental group, received 100 mg/kg PTX a week before MDMA administration, second experimental group received 100 mg/kg PTX Just in the time of the third injection of MDMA and the third experimental group received 100 mg/kg PTX followed by one dose of MDMA. Two weeks later, kidneys were removed and prepared for H&E staining, TUNEL and western blot techniques. 
 Results: histopathological studies showed significantly decrease in the kidney cellular damage, in experimental group 1 compared to MDMA group. The number of TUNEL-positive cells was increased significantly in MDMA group. A significant difference was revealed in the mean number of TUNEL-positive cells between the rats treated with PTX before MDMA administration and MDMA group. Expression of active caspase-3 was significantly increased in the MDMA group. While the PTX treatment could significantly decrease when administrated before MDMA injections.
 Conclusion: Pentoxifylline can significantly reduce the severity of lesions in the kidney following administration of MDMA.

Highlights

  • The 3,4-methylenedioxymethamphetamine (MDMA) as know ecstasy, is one of the most popular used drugs as a recreational drug by young people [1].There are increasing evidence of its toxicity, MDMA has been considered as a safe drug

  • It has been shown that MDMA induces cell death trough an apoptotic pathway by releasing of cytochrome C and caspase cascade activation [4].Cell deaths have been classified by consensus of opinions such as apoptosis, necrosis, necroptosis, autophagy and cornification [5]

  • A minimum of 20 fields was examined in each sample.In Situ Apoptosis Assay by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining Kidneys were perfused with phosphate-buffered saline (PBS) (50 ml) using the transcardiac approach, followed by 4% phosphate-buffered formalin

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Summary

Introduction

The 3,4-methylenedioxymethamphetamine (MDMA) as know ecstasy, is one of the most popular used drugs as a recreational drug by young people [1].There are increasing evidence of its toxicity, MDMA has been considered as a safe drug. Effect of PTX on Kidney’s Cells apoptosis induced by MDMA species (ROSs) [3]. The objectives of the present study were to investigate the possible protective effects of PTX the kidney’ cells apoptosis due to acute administration of MDMA. As Pentoxifylline (PTX) increases cAMP and reduces tumor necrosis factor-α, the present study aimed to investigate the effect of PTX on kidney damage induced by acute administration of MDMA in the male rat. The number of TUNEL-positive cells was increased significantly in MDMA group. A significant difference was revealed in the mean number of TUNEL-positive cells between the rats treated with PTX before MDMA administration and MDMA group. While PTX treatment when administrated before MDMA injections could significantly decrease the caspase-3 activity. Conclusion: The PTX can substantially reduce the severity of lesions in the kidney following administration of MDMA. [GMJ.2016;5(3):131-138]

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