Allopurinol Protective Effect of Renal Ischemia by Downregulating TNF-α, IL-1β, and IL-6 Response.

Beatriz Prieto-Moure, José M Lloris-Carsí, Mariola Belda-Antolí, Luis H Toledo-Pereyra, Dolores Cejalvo-Lapeña

Journal of investigative surgery : the official journal of the Academy of Surgical Research 2017 Jun

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Allopurinol is a well-known antioxidant that protects tissue against ischemia and reperfusion injury, blocking purine catabolism, and possibly reducing TNF-α and other cytokines. It also plays a significant role in reducing the inflammatory processes by inhibiting chemotaxis and other inflammatory mediators. The objective of this study was to define the role of allopurinol regarding kidney ischemic injury particularly as to its effect on inflammatory molecules such as TNF-α, IL-1β, and IL-6 response. One hundred and twenty five rats were subjected to warm renal ischemia. Five more animals were included as sham. Animal survival and plasma levels of lipid peroxidation, myeloperoxidase, lactate dehydrogenase, glutathione, urea, creatinine, and cytokines were determined. Inflammatory parameters (TNF-α, IL-1β, and IL-6) were measured in all groups by quantitative immunosorbent assay. Further, immunohistological and histopathological studies were carried out on animals treated prior to, or following reperfusion with 10 and 50 mg/kg of Allopurinol. The statistical analysis included ANOVA and Fisher test as well as χ2 test. Significance was reached at a p < 0.05. The results of this study indicated that Allopurinol protected against kidney ischemia-reperfusion injury since significantly better results of survival, biochemical analysis, and histopathological testing were observed in treated animals as compared to ischemic controls. In conclusion, Allopurinol protected ischemic kidneys through a mechanism associated with downregulation of TNF-α, IL-1 β, and IL-6, in addition to other well-known effects such as decreased lipid peroxidation and neutrophil activity. It also increased antioxidant capacity and diminished endogenous peroxidase stain in renal ischemic tissue. Therefore, this experiment showed an effectiveness of allopurinol protection against proteomic and morphological damage.

Citation

Beatriz Prieto-Moure, José M Lloris-Carsí, Mariola Belda-Antolí, Luis H Toledo-Pereyra, Dolores Cejalvo-Lapeña. Allopurinol Protective Effect of Renal Ischemia by Downregulating TNF-α, IL-1β, and IL-6 Response. Journal of investigative surgery : the official journal of the Academy of Surgical Research. 2017 Jun;30(3):143-151