Resveratrol’s Antiapoptotic and Antioxidant Role in Carbon Tetrachloride-Induced Nephrotoxicity of Rats

Abstract

This study investigates the protective effect of Resveratrol on renal tissues utilizing histopathology, immunohistochemistry, and immunofluorescence methods in a carbon tetrachloride (CCl4)-induced nephrotoxicity model. Wistar albinos (male, n=32) were randomly selected and divided into groups. The initial control group, followed by the second group, received CCl4 (2mg/kg), the third group was administered Resveratrol (30 mg/kg/day), and the fourth group was co-administered with CCl4 and Resveratrol. After the experiment, rats were euthanized under anesthesia, and their kidneys were collected. Results revealed that in the CCl4 group, notable degeneration and necrosis of tubular epithelium, significant steatosis, and arterial hyperemia wereobserved. In the CCl4+Resveratrol group, renal tissues exhibited slight deterioration of tubular epithelium and hyperemia in the glomerular arteries. The immunohistochemistry approach employing 8- Hydroxy-deoxyguanosine (8-OHdG) was utilized to identify DNA damage in kidney tissue. Immunohistochemistry results indicated that both the control and resveratrol groups had a negative reaction for 8-OHdG, but the CCl4 group demonstrated a statistically significant increase in 8-OHdG expression in the tubular epithelium located cytoplasmically (p<0.05). Modest cytoplasmic presence was detected in the CCl4+Resveratrol group. The immunofluorescence approach utilizing caspase 3 was employed to identify apoptosis in kidney tissue. The results indicated that the CCl4 group demonstrated a statistically significant increase in intracytoplasmic caspase 3 expression in the tubular epithelium compared to other groups (p<0.05) while a minor intracytoplasmic response for caspase 3 was observed in the CCl4+Resveratrol group. As a conclusion, resveratrol demonstrated strong antioxidant, antiapoptotic, and DNA-protective effects in a CCl-4-induced nephrotoxicity rat model and can be added to the daily diet for better kidney health against CCl-4-induced nephrotoxicity.

Keywords

• Antioxidant
• Caspase 3
• CCl4
• Resveratrol
• 8-OHdG

Ratlarda Karbon Tetraklorür ile Oluşturulan Nefrotoksisitede Resveratrol’ün Antiapoptotik ve Antioksidan Rolü

Abstract

Bu çalışma, karbon tetraklorür (CCl4) kaynaklı nefrotoksisite modelinde histopatoloji, immünohistokimya ve immünofloresan metotlarını kullanarak güçlü bir antioksidan olan Resveratrol'ün böbrek dokuları üzerindeki koruyucu etkisini incelemeyi amaçlamaktadır. Rastgele seçilen erkek Wistar sıçanları (n=32) dört gruba ayrıldı. Kontrol grubuna herhangi bir işlem uygulanmazken, ikinci gruba CCl4 (2 mg/kg), ve üçüncü gruba Resveratrol (30 mg/kg/gün) verildi ve dördüncü gruba CCl4 ve Resveratrol birlikte verildi. Deneyden sonra sıçanlara anestezi altında ötenazi uygulandı ve böbrek örnekleri toplandı. CCl4 grubunda histopatolojik olarak, tübüler epitelyumda belirgin dejenerasyon ve nekroz, hem glomerüler hem de interstisyel bölgede yer alan arterlerde belirgin steatoz ve hiperemi görüldü. CCl4+Resveratrol grubunda böbrek dokuları tübüler epitelde hafif bozulma ve glomerüler ve interstisyel alanların arterlerinde hiperemi gösterdi. Böbrek dokusunda DNA hasarını belirlemek için 8-OHdG antikoru ile immünohistokimyasal boyama yapıldı. İmmünohistokimya sonuçları hem kontrol hem de resveratrol gruplarında 8-OHdG antikoruna karşı bir reaksiyon oluşmadığını, ancak CCl4 grubuna ait tübüler epitelde sitoplazmik 8-OHdG ekspresyonunda istatistiksel olarak anlamlı bir artış görüldüğünü ortaya koydu (p<0.05). CCl4+Resveratrol grubunda hafif intrasitoplazmik tutulum tespit edildi. Böbrek dokusunda apoptozu belirlemek için kaspaz 3 antikoru ile immünofloresan boyaması yapıldı. Sonuçlar, CCl4 grubunun tübüler epitelde diğer gruplara kıyasla intrasitoplazmik kaspaz 3 ekspresyonunda istatistiksel olarak anlamlı bir artış gösterdiğini (p<0.05) ortaya koyarken, CCl4+Resveratrol grubundakaspaz 3'e karşı oluşan yanıt minör ve intrasitoplazmik özellikteydi. Sonuç olarak, resveratrol, CCl-4 kaynaklı nefrotoksisite sıçan modelinde güçlü antioksidan, antiapoptotik ve DNA koruyucu etkiler göstermiştir ve CCl-4 kaynaklı nefrotoksisiteye karşı daha iyi böbrek sağlığı için günlük diyete eklenebilir.

Keywords

• Antioksidan
• CCl4
• Kaspaz 3
• Resveratrol
• 8-OHdG

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