Biochemical and Histological Evaluation of The Impacts of Conivaptan and Boric Acid on Ischemia-induced Tissue Injury

Öz

Ischemia-reperfusion (I/R) injury, which is a major cause of acute kidney injury (AKI), involves complicated pathophysiological process triggered by oxidative and inflammatory mechanisms. This process adversely affects kidneys and distant organs/systems, potentially leading to multiple organ failure. Therefore, experimental studies targeting renal I/R injury mechanisms are needed to mitigate local and distant organ damage. We established an experimental renal I/R rat model to mimic the clinical presentation of AKI and evaluated the potential damage-preventive effects of conivaptan (CON) and boric acid (BA) on kidneys and distant tissues (liver, brain, heart, pancreas, testis, spleen). Accordingly, rats were divided into the groups: Control (sham-operated), Ischemia–reperfusion (I/R), I/R + Dimethyl sulfoxide (I/R + DMSO) I/R + Conivaptan (I/R + CON), and I/R + Conivaptan + Boric acid (I/R + CON + BA). TAS, TOS, and total thiol levels, which indicated oxidant and antioxidant redox status, were measured in blood samples, and the oxidative stress index was calculated. Inflammation-related cytokines (TNF-α, interleukin (IL)-6, IL-10, IL-35, and chemerin) were analysed through ELISA and/or RT-PCR. Furthermore, serum enzyme activities, lipid-profile, and albumin levels were determined. Tissue samples were examined histologically using Hematoxylin-Eosin staining. Renal I/R injury significantly increased systemic oxidative stress, exacerbated renal inflammation, and induced distant organ damage. Treatment with CON and BA demonstrated protective effects by reducing oxidative stress and modulating inflammatory responses without inducing toxicity in the postischemic period. Our findings suggest that CON and BA exhibit anti-inflammatory and antioxidant properties in the early phase of postischemic injury process and may be effective in attenuating distant organ damage following renal I/R injury.

Anahtar Kelimeler

• Boric acid
• Conivaptan
• Inflammation
• Acute kidney injury
• Ischemia-reperfusion
• Oxidative stress

Konivaptan ve Borik Asidin İskemi Kaynaklı Doku Hasarı Üzerindeki Etkilerinin Biyokimyasal ve Histolojik Açıdan Değerlendirilmesi

Öz

Akut böbrek hasarının (ABH) başlıca nedenlerinden biri olan iskemi-reperfüzyon (İ/R) hasarı, oksidatif ve inflamatuar mekanizmaların tetiklendiği kompleks patofizyolojik süreçleri içermektedir. Bu süreçler, böbrek ve uzak organ/sistemleri olumsuz etkileyerek çoklu organ yetmezliğine yol açabilmektedir. Bu nedenle, lokal ve uzak organ hasarını azaltmaya yönelik, böbrek İ/R hasarı mekanizmalarını hedef alan deneysel çalışmaların planlanması önemli bir ihtiyaçtır. Bu çalışmada, ABH kliniğini yansıtmak için deneysel bir böbrek İ/R sıçan modeli oluşturulmuştur; konivaptan (CON) ve borik asidin (BA) böbrekler ve uzak dokular (karaciğer, beyin, kalp, pankreas, testis, dalak) üzerindeki potansiyel hasar önleyici etkileri araştırılmıştır. Buna göre, sıçanlar Kontrol (sham-opere), İskemi-reperfüzyon (I/R), I/R + Dimetilsülfoksit (I/R + DMSO), I/R + Konivaptan (I/R + CON) ve I/R + Konivaptan + Borik asit (I/R + CON + BA) olmak üzere gruplara ayrılmıştır. Oksidan ve antioksidan redoks durumunu gösteren TAS, TOS ve total tiyol düzeyleri kan örneklerinde ölçülmüştür ve oksidatif stres indeksi hesaplanmıştır. İnflamasyonla ilişkili sitokinler (TNF-α, interlökin (IL)-6, IL-10, IL-35 ve kemerin) ELISA ve/veya RT-PCR ile analiz edilmiştir. Ayrıca, serum enzim aktiviteleri, lipit profili ve albümin düzeyleri belirlenmiştir. Doku örnekleri Hematoksilen-Eozin boyama kullanılarak histolojik olarak incelenmiştir. Çalışmamızda böbrek I/R hasarının sistemik oksidatif stresi önemli ölçüde artırdığı, böbrek inflamasyonunu şiddetlendirdiği ve uzak organ hasarını indüklediği gözlenmiştir. CON ve BA tedavisi, iskemi sonrası dönemde toksisiteye neden olmadan oksidatif stresi azaltarak ve inflamasyon yanıtlarını düzenleyerek koruyucu etki göstermiştir. Bulgularımız, CON ve BA'nın iskemi sonrası hasar sürecinin erken evresinde anti-inflamatuar ve antioksidan özellikler gösterdiğini ve böbrek I/R hasarını takiben uzak organ hasarını hafifletmede etkili olabileceğini destekler niteliktedir.

Anahtar Kelimeler

• Borik asit
• Konivaptan
• İnflamasyon
• Akut böbrek hasarı
• İskemi-reperfüzyon
• Oksidatif stres

Kaynakça

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