Protective effects of insulin-like growth factor (IGF-1) in doxorubicin-induced experimental liver and kidney injury

Osman Çiftçi; Münevver Nazlıcan Kaplan; Özlem Özmen

Article Details

Protective effects of insulin-like growth factor (IGF-1) in doxorubicin-induced experimental liver and kidney injury

Authors:

Osman Çiftçi | Münevver Nazlıcan Kaplan | Özlem Özmen

Publisher:

Cukurova University

Main Topics:

Klinik Tıp Bilimleri (Diğer)

Journal:

Cukurova Medical Journal Vol.50 Issue 2, pp.410-419

Document Type:

Article

Publication Date:

6/2025

Document Language:

English

Document ID (Org No.):

2001351455

pISSN:

2602-3032

Keywords:

Abstract:

 Purpose: This study aimed to investigate the protective effects of insulin-like growth factor-1 IGF-1 against doxorubicin DOX-induced liver and kidney damage in rats using biochemical, immunohistochemical, and histopathological methods. Materials and Methods: A total of 32 Wistar albino rats were randomly assigned into four groups: Control, DOX 4 mgkgweek, IGF-1 1 µgkg daily, and DOX  IGF-1 DOX 4 mgkgweek  IGF-1 1 µgkg daily. After the four-week experimental protocol, blood, liver, and kidney tissues were collected under anesthesia. Serum levels of alanine aminotransferase ALT, aspartate aminotransferase AST, blood urea nitrogen BUN, urea, and creatinine were analyzed biochemically. Total antioxidant status TAS and total oxidant status TOS in liver and kidney tissues were measured using ELISA. Gene expression levels of HIF-1α and iNOS were evaluated by real-time PCR. Histopathological and immunohistochemical Caspase-3, TNF-α, and FGF-2 evaluations were conducted on liver and kidney tissues. Results: DOX significantly increased serum ALT, AST, BUN, urea, and creatinine levels and elevated TOS while reducing TAS in tissues. HIF-1α expression was markedly upregulated 5.50-fold, indicating oxidative damage. IGF-1 administration reduced serum ALT, AST, BUN, urea, and creatinine levels, increased TAS, and decreased TOS. Expression levels of HIF-1α and iNOS approached those of the control group. DOX caused significant histopathological damage and increased Caspase-3 and TNF-α expressions in the liver and Caspase-3 and FGF-2 expressions in the kidney. These alterations were ameliorated by IGF-1 treatment. Conclusion: The findings suggest that IGF-1 exerts protective effects against DOX-induced hepatorenal toxicity, possibly through its antioxidant, anti-inflammatory, and anti-apoptotic properties.

 Purpose: This study aimed to investigate the protective effects of insulin-like growth factor-1 IGF-1 against doxorubicin DOX-induced liver and kidney damage in rats using biochemical, immunohistochemical, and histopathological methods. Materials and Methods: A total of 32 Wistar albino rats were randomly assigned into four groups: Control, DOX 4 mgkgweek, IGF-1 1 µgkg daily, and DOX  IGF-1 DOX 4 mgkgweek  IGF-1 1 µgkg daily. After the four-week experimental protocol, blood, liver, and kidney tissues were collected under anesthesia. Serum levels of alanine aminotransferase ALT, aspartate aminotransferase AST, blood urea nitrogen BUN, urea, and creatinine were analyzed biochemically. Total antioxidant status TAS and total oxidant status TOS in liver and kidney tissues were measured using ELISA. Gene expression levels of HIF-1α and iNOS were evaluated by real-time PCR. Histopathological and immunohistochemical Caspase-3, TNF-α, and FGF-2 evaluations were conducted on liver and kidney tissues. Results: DOX significantly increased serum ALT, AST, BUN, urea, and creatinine levels and elevated TOS while reducing TAS in tissues. HIF-1α expression was markedly upregulated 5.50-fold, indicating oxidative damage. IGF-1 administration reduced serum ALT, AST, BUN, urea, and creatinine levels, increased TAS, and decreased TOS. Expression levels of HIF-1α and iNOS approached those of the control group. DOX caused significant histopathological damage and increased Caspase-3 and TNF-α expressions in the liver and Caspase-3 and FGF-2 expressions in the kidney. These alterations were ameliorated by IGF-1 treatment. Conclusion: The findings suggest that IGF-1 exerts protective effects against DOX-induced hepatorenal toxicity, possibly through its antioxidant, anti-inflammatory, and anti-apoptotic properties.

 Purpose: This study aimed to investigate the protective effects of insulin-like growth factor-1 IGF-1 against doxorubicin DOX-induced liver and kidney damage in rats using biochemical, immunohistochemical, and histopathological methods. Materials and Methods: A total of 32 Wistar albino rats were randomly assigned into four groups: Control, DOX 4 mgkgweek, IGF-1 1 µgkg daily, and DOX  IGF-1 DOX 4 mgkgweek  IGF-1 1 µgkg daily. After the four-week experimental protocol, blood, liver, and kidney tissues were collected under anesthesia. Serum levels of alanine aminotransferase ALT, aspartate aminotransferase AST, blood urea nitrogen BUN, urea, and creatinine were analyzed biochemically. Total antioxidant status TAS and total oxidant status TOS in liver and kidney tissues were measured using ELISA. Gene expression levels of HIF-1α and iNOS were evaluated by real-time PCR. Histopathological and immunohistochemical Caspase-3, TNF-α, and FGF-2 evaluations were conducted on liver and kidney tissues. Results: DOX significantly increased serum ALT, AST, BUN, urea, and creatinine levels and elevated TOS while reducing TAS in tissues. HIF-1α expression was markedly upregulated 5.50-fold, indicating oxidative damage. IGF-1 administration reduced serum ALT, AST, BUN, urea, and creatinine levels, increased TAS, and decreased TOS. Expression levels of HIF-1α and iNOS approached those of the control group. DOX caused significant histopathological damage and increased Caspase-3 and TNF-α expressions in the liver and Caspase-3 and FGF-2 expressions in the kidney. These alterations were ameliorated by IGF-1 treatment. Conclusion: The findings suggest that IGF-1 exerts protective effects against DOX-induced hepatorenal toxicity, possibly through its antioxidant, anti-inflammatory, and anti-apoptotic properties.

 Amaç: Bu çalışmanın amacı, biyokimyasal, immünohistokimyasal ve histopatolojik yöntemler kullanılarak sıçanlarda doksorubisin DOX kaynaklı karaciğer ve böbrek hasarına karşı insülin benzeri büyüme faktörü-1in IGF-1 koruyucu etkilerinin araştırılmasıdır. Gereç ve Yöntem: Toplam 32 Wistar albino sıçanı rastgele dört gruba ayrıldı: Kontrol, DOX 4 mgkghafta, IGF-1 günlük 1 µgkg ve DOX  IGF-1 DOX 4 mgkghafta  IGF-1 1 µgkg günlük. Dört haftalık deneysel protokolden sonra, anestezi altında kan, karaciğer ve böbrek dokuları toplandı. Alanin aminotransferaz ALT, aspartat aminotransferaz AST, kan üre azotu BUN, üre ve kreatinin serum seviyeleri biyokimyasal olarak analiz edildi. Karaciğer ve böbrek dokularındaki toplam antioksidan durum TAS ve toplam oksidan durum TOS ELISA kullanılarak ölçüldü. HIF-1α ve iNOS gen ekspresyon seviyeleri gerçek zamanlı PCR ile değerlendirildi. Karaciğer ve böbrek dokularında histopatolojik ve immünohistokimyasal Kaspaz-3, TNF-α ve FGF-2 değerlendirmeler yapıldı. Bulgular: DOX, serum ALT, AST, BUN, üre ve kreatinin seviyelerini önemli ölçüde artırdı ve dokularda TASı azaltırken TOSu yükseltti. HIF-1α ekspresyonu belirgin şekilde yukarı düzenlendi 5,50 kat, bu da oksidatif hasarı gösteriyordu. IGF-1 uygulaması serum ALT, AST, BUN, üre ve kreatinin seviyelerini düşürdü, TASı artırdı ve TOSu azalttı. HIF-1α ve iNOS ekspresyon seviyeleri kontrol grubundakilere yaklaştı. DOX, karaciğerde önemli histopatolojik hasara ve artan Kaspaz-3 ve TNF-α ifadelerine ve böbrekte Kaspaz-3 ve FGF-2 ifadelerine neden oldu. Bu değişiklikler IGF-1 tedavisiyle iyileştirildi. Sonuç: Bulgular, IGF-1in muhtemelen antioksidan, anti-inflamatuar ve anti-apoptotik özellikleri yoluyla DOX kaynaklı hepatorenal toksisiteye karşı koruyucu etkiler uyguladığını göstermektedir.

Article Details

Protective effects of insulin-like growth factor (IGF-1) in doxorubicin-induced experimental liver and kidney injury

Authors:

Osman Çiftçi | Münevver Nazlıcan Kaplan | Özlem Özmen

Publisher:

Cukurova University

Main Topics:

Klinik Tıp Bilimleri (Diğer)

Journal:

Cukurova Medical Journal Vol.50 Issue 2, pp.410-419

Document Type:

Article

Publication Date:

6/2025

Document Language:

English

Document ID (Org No.):

2001351455

pISSN:

2602-3032

Doxorubusin

Oxidative Damage

IGF-1

hepatotoxicity

nephrotoxicityDoksorubusin

Hepatotoksite

IGF-1

Oksidatif Hasar

Nefrotoksisite

Issues

Article Details

Authors: Osman Çiftçi | Münevver Nazlıcan Kaplan | Özlem Özmen

Publisher: Cukurova University

Main Topics: Klinik Tıp Bilimleri (Diğer)

Journal: Cukurova Medical Journal Vol.50 Issue 2, pp.410-419

Document Type: Article

Publication Date: 6/2025

Document Language: English

Document ID (Org No.): 2001351455

pISSN: 2602-3032

Issues

Authors:

Osman Çiftçi | Münevver Nazlıcan Kaplan | Özlem Özmen

Publisher:

Cukurova University

Main Topics:

Klinik Tıp Bilimleri (Diğer)

Journal:

Cukurova Medical Journal Vol.50 Issue 2, pp.410-419

Document Type:

Article

Publication Date:

6/2025

Document Language:

English

Document ID (Org No.):

2001351455

pISSN:

2602-3032