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Clopidogrel protects against gentamicin-induced nephrotoxicity through targeting oxidative stress, apoptosis, and
Asmaa A Akila1, Rania A Gad2, Mohamed Gamal El-Din Ewees3
1Molecular Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, 62511, Egypt.
Abstract:
Gentamicin (Genta)-induced nephrotoxicity poses a significant clinical challenge due to its detrimental effects on kidney function. Clopidogrel (Clop), an antiplatelet drug known for its ability to prevent blood clots by inhibiting platelet aggregation, also has potential effects on oxidative stress and cell death. This study investigates Clop's protective role against Genta-induced nephrotoxicity, emphasizing the importance of the coagulation cascade. The 32 adult male albino rats were randomly assigned to four groups of eight (n = 8). The first group received only the vehicle. Genta was injected intraperitoneally at 100 mg/kg/day for 8 days in the second group. Groups 3 and 4 received oral Clop at 10 and 20 mg/kg/day for 1 week before Genta delivery and throughout the experiment. Renal tissue showed renal function tests, oxidative stress, pro-inflammatory cytokines, apoptotic markers, coagulation profile, and fibrin expression. Clop improved Genta-induced kidney function and histopathology. Clop substantially reduced pro-inflammatory cytokines, oxidative stress indicators, pro-apoptotic proteins, and fibrin protein. Clop also significantly boosted renal tissue anti-inflammatory and anti-apoptotic protein expression. Genta-induced nephrotoxicity involves oxidative stress, apoptosis, and coagulation system activation, according to studies. This study underscores that Genta-induced nephrotoxicity is associated with oxidative stress, apoptosis, and activation of the coagulation system. Clop's protective effects on nephrons are attributed to its anticoagulant, antioxidant, anti-inflammatory, and anti-apoptotic properties, presenting it as a promising therapeutic strategy against Genta-induced kidney damage.
Insights
Clopidogrel (Clop) protects against gentamicin (Genta)-induced kidney damage by reducing oxidative stress, inflammation, and apoptosis. This study highlights Clop
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Gentamicin (Genta) causes nephrotoxicity, a significant clinical issue.
- Clopidogrel (Clop), an antiplatelet agent, may possess protective properties against drug-induced kidney damage.
- The role of the coagulation cascade in Genta-induced nephrotoxicity requires further investigation.
Purpose of the Study:
- To investigate the protective effects of Clopidogrel against Gentamicin-induced nephrotoxicity in a rat model.
- To elucidate the mechanisms underlying Clopidogrel's renoprotective effects, focusing on oxidative stress, apoptosis, and coagulation.
- To assess the impact of Clopidogrel on renal function, histopathology, and molecular markers.
Main Methods:
- Adult male albino rats were divided into four groups: control, Genta-only, and two Genta groups pre-treated with different doses of Clopidogrel.
- Genta was administered intraperitoneally, while Clopidogrel was given orally prior to and during Genta exposure.
- Renal function, oxidative stress markers, pro-inflammatory cytokines, apoptotic markers, coagulation profile, and fibrin expression were analyzed in renal tissues.
Main Results:
- Clopidogrel treatment significantly improved kidney function and renal histopathology in Genta-treated rats.
- Clopidogrel administration markedly reduced levels of pro-inflammatory cytokines, oxidative stress indicators, and pro-apoptotic proteins.
- The drug also decreased fibrin protein expression and enhanced the expression of anti-inflammatory and anti-apoptotic proteins in renal tissues.
Conclusions:
- Gentamicin-induced nephrotoxicity is linked to oxidative stress, apoptosis, and activation of the coagulation system.
- Clopidogrel exhibits significant renoprotective effects against Genta-induced kidney damage.
- These protective effects are attributed to Clopidogrel's combined anticoagulant, antioxidant, anti-inflammatory, and anti-apoptotic properties, positioning it as a potential therapeutic agent.
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