Thymoquinone ameliorates acute kidney injury induced by renal ischemia-reperfusion / La timoquinona mejora la lesión renal aguda inducida por isquemia-reperfusión renal

SUMMARY: Renal ischemia-reperfusion injury (IRI)is an unavoidable consequence in renal transplantation and multiple clinical settings. A debate has been raised about the particular role of hypoxia-inducible factor (HF-1α) in the renal injury pathogenesis and the renal cortex ultrastructural alterations. Also, we investigated the antioxidant/anti-inflammatory effect of thymoquinone and its modulatory role on HIF-1α in protection against renal IRI.Adult male Wister albino rats were assigned into 3 groups (n=16); 1) Sham-operated, 2) IRI model and 3) renal IRI pre-treated with thymoquinone 10 mg.kg-1.day-1 (TQ-IRI) for 10 days and at the reperfusion onset. Following the operation, 8 rats from each group were euthanized after 3 hours and the remaining 8 rats at 24 hours. Renal injury was assessed by the increased blood urea nitrogen, creatinine level, and the EGTI histological injury scoreat both 3 and 24h. HIF-1α was upregulated (p<0.01) and was correlated with renal tissue reactive oxygen species (ROS) production and total oxidant capacity (TAC) consumption. Elevated inflammatory markers (NFkB, MCP-1 and VCAM-1) were associated with renal IRI.Thymoquinone treatment inhibited the accumulation of HIF-1α (p<0.01), reduced renal oxidation/inflammation process and markedly diminished renal injury.

RESUMEN: La lesión por isquemia-reperfusión renal (IRR) es una consecuencia inevitable en el trasplante renal como también en múltiples contextos clínicos. Se ha suscitado una discusión referente a la relación particular del factor inducible por hipoxia (HF- 1α) en la patogénesis de la lesión renal y las alteraciones ultraestructurales de la corteza renal. Además, investigamos el efecto antioxidante / antiinflamatorio de la timoquinona y su papel modulador sobre HIF-1α en la protección contra IRR. Se utilizaron ratas albinas Wister macho adultas divididas en 3 grupos (n = 16); 1) Intervención simulada, 2) modelo IRR y 3) IRR pretratado con timoquinona 10 mg/kg-1. día-1 (TQ-IRR) durante 10 días y al inicio de la reperfusión. Posterior a la operación, 8 ratas de cada grupo fueron sacrificadas después de 3 horas y las 8 ratas restantes a las 24 horas. La lesión renal se evaluó por el aumento de nitrógeno ureico en sangre, el nivel de creatinina y la puntuación de lesión histológica EGTI tanto a las 3 como a las 24 horas. HIF-1α se incrementó (p <0,01) y se correlacionó con la producción de especies de oxígeno reactivo (ROS) del tejido renal y el consumo de capacidad oxidante total. Los marcadores inflamatorios elevados (NFkB, MCP-1 y VCAM-1) se asociaron con IRR. El tratamiento con timoquinona inhibió la acumulación de HIF-1α (p <0,01), redujo el proceso de oxidación / inflamación renal y disminuyó notablemente la lesión renal.

Effects of thymoquinone against cisplatin-induced cardiac injury in rats

PURPOSE: T o investigate the possible protective effect of thymoquinone (TQ) in cisplatin (CP) induced myocardial injury. METHODS: A total of 28 adult male Wistar-Albino rats were randomly and equally divided into four groups as follows: Group 1 (control), Group 2 (CP at 15 mg/kg dose), Group 3 (TQ 40 mg/kg/day for two days prior to CP injection and on third day, CP at 15 mg/kg dose was intraperitoneally administered and TQ treatment continued until fifth day) and Group 4 (TQ at 40mg/kg/day dose for five days). RESULTS: There was a significant increment in CP group in terms of congestion, edema and pycnotic nuclei in myocardial fibers, comparing with other groups. TQ group exhibited significant increase in expression of antiapoptotic protein Bcl-2, comparing with CP group (p<0.05). In only CP administered group, expression of antiapoptotic protein Bcl-2 was lowest comparing with other groups. CONCLUSION: Established data indicate that cisplatin is cardiotoxic and thymoquinone may be useful in treating CP-induced cardiac injury.