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Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in
F V Pinheiro1, V C Pimentel, K S De Bona
1Universidade Federal de Santa Maria, Brazil.
Abstract:
The methotrexate (MTX) is an anti-folate used to treat cancer and some inflammatory diseases. The efficacy of MTX is often limited by its severe toxicity. The present study was undertaken to determine whether Grape seed (Cabernet Sauvignon) extract (GSE) could ameliorate the MTX-induced oxidative injury and the effect on adenosine deaminase activity (ADA) in rats. The rats were pretreated with 50 mg/kg of GSE, i.p., prior to MTX administration (10 mg/kg, i.p.) with a second dose given 4 h and a third dose 16 h after MTX administration. Biochemical parameters were investigated 48 h after the last MTX administration. The administration of MTX increased thiobarbituric acid reactive species (TBARS) levels in hippocampus, kidney and liver, whereas induced a significant decreased in the ADA activity in the cerebral cortex, kidney and liver tissues. MTX administration significantly increased the activity of ALT(alanine aminotransferase) and urea levels and decreased uric acid levels in the serum. Urinary uric acid levels decreased in the MTX group when compared to those of the control group. The GSE along with MTX-administration significantly reversed these parameters toward to near normal. These results indicated that GSE could reduce hepatic and nephritic damage induced by MTX-treatment in young rats therefore having free radical scavenging.
Insights
Grape seed extract (GSE) can protect against methotrexate (MTX) toxicity. GSE reduced oxidative damage and normalized adenosine deaminase activity in rats treated with MTX, indicating its potential as a protective agent.
Area of Science:
- Pharmacology and Toxicology
- Natural Product Chemistry
- Biochemistry
Background:
- Methotrexate (MTX) is a vital anti-folate drug for cancer and inflammatory diseases.
- MTX efficacy is often compromised by significant toxicity, including oxidative stress.
- Grape seed extract (GSE) is recognized for its antioxidant properties.
Purpose of the Study:
- To investigate the protective effects of GSE against MTX-induced oxidative injury in rats.
- To evaluate the impact of GSE on adenosine deaminase (ADA) activity following MTX administration.
- To assess GSE's potential to mitigate MTX-induced hepatic and nephritic damage.
Main Methods:
- Rats were pretreated with GSE (50 mg/kg) before and after MTX (10 mg/kg) administration.
- Biochemical parameters, including TBARS, ADA activity, ALT, urea, and uric acid, were measured.
- Tissue samples from hippocampus, kidney, liver, and cerebral cortex were analyzed.
Main Results:
- MTX administration increased oxidative stress markers (TBARS) and altered biochemical parameters (ALT, urea, uric acid).
- MTX significantly decreased adenosine deaminase (ADA) activity in multiple tissues.
- GSE pretreatment significantly reversed MTX-induced biochemical changes, restoring parameters near normal levels.
Conclusions:
- GSE exhibits significant protective effects against MTX-induced hepatic and nephritic damage in rats.
- The free radical scavenging activity of GSE contributes to its ameliorative effects.
- GSE demonstrates potential as a therapeutic adjunct to reduce MTX toxicity.