Time-Dependent Molecular Changes Following MDMA-Induced Nephrotoxicity.
Mehrdad Roghani, Ravieh Golchoobian, Maryam Mohammadian, Farzane Shanehbandpour-Tabari, Zahra Salehi, Saba Gilaki-Bisheh
Iranian journal of pharmaceutical research : IJPR January 1, 2024 DOI: 10.5812/ijpr-145483 via PubMed
Summary
AI-generated from the abstractA single moderate dose of MDMA (20 mg/kg) given to rats caused a temporary rise in blood markers of kidney stress (BUN and creatinine), but no structural damage to kidney tissue was observed. Levels of the inflammatory signaling proteins TNF-α and TGF-β decreased in kidney tissue. Expression of genes related to cell death (Bax and Bcl-xl) was reduced, while Bcl-2 expression and actual cell death (apoptosis) did not change significantly. The findings suggest that MDMA may disrupt cytokine pathways, particularly lowering TGF-β, which could be linked to reduced TNF-α, rather than causing direct tissue injury or cell death.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | MDMA |
| Dose | 20 mg/kg |
| Topics | MDMA |
| Keywords | 3,4-methylenedioxymethamphetamine Acute kidney injury Apoptosis Inflammation Ecstasy MDMA |
| Citations | 1 |
| Key finding | A single dose of MDMA caused transient kidney function changes and reduced TNF-α and TGF-β levels in rat kidney tissue without structural damage or significant apoptosis. |
Abstract
The increasing recreational use of ecstasy (MDMA) poses significant risks to human health, including reports of fatal renal failure due to its adverse renal effects. While MDMA-induced renal toxicity might result from systemic effects, there is also substantial evidence of direct harm to renal tissues by MDMA or its metabolites. The precise mechanisms underlying renal toxicity remain unclear. This study explored the impact of a single intraperitoneal dose of MDMA (20 mg/kg) on rat kidneys. Serum BUN and creatinine levels were evaluated to assess renal function, while TNF-α and TGF-β protein concentrations were measured using ELISA. mRNA levels of Bax, Bcl-xl, and Bcl-2 were quantified using quantitative RT-PCR. Additionally, apoptosis and histopathological changes in renal tissue were examined. Results showed a transient increase in serum BUN and creatinine in MDMA-treated rats. There were decreases in TNF-α and TGF-β levels in the renal tissue. Both pro-apoptotic Bax and anti-apoptotic Bcl-xl gene expressions were significantly reduced, whereas Bcl-2 expression and apoptosis did not show significant changes. No structural alterations were observed in the renal tissues. Overall, this study suggests that the renal adverse effects of MDMA may be mediated through the disruption of cytokine pathways, with notable reductions in TGF-β possibly linked to decreased TNF-α levels.