Abstract
Background Recent studies indicate hyperuricemia as an aggravating factor for kidney diseases progression. Basic research for novel agents to reduce hyperuricemia and kidney abnormalities will be highly rewarding. Herein, we report Thymoquinone (Tq) as an active constituent of Nigella sativa to have renal protective effective against oxonic acid (OA)-induced hyperuricemia, hypertension, and renal oxidative stress in rat models. Methods OA 750 mg/kg BW for 12 weeks was used to induce uricemia in Sprague dawley rats. Tq at 10 and 20 mg/kg BW were administered along with OA for treatment groups. Plasma uric acid concentration and systolic blood pressure were measured. Oxidative stress markers, total ATP content, and membrane bound ATPases were measured in renal mitochondria. Anti-oxidant enzymes were analyzed in the renal tissues. Apoptosis in renal tissue was detected. Key signaling proteins for apoptosis, oxidative stress, and lipid oxidation pathways were determined. Results OA induced both circulating uric acid levels and hypertension in the control group which was brought down on Tq treatments. Tq effectively prevented accumulation of uric acid and oxidative stress in the renal tissues. Tq also proved to increase the total ATP content of the renal mitochondria and prevented the apoptosis induced by OA. Tq increased the expressions of phosphorylated Akt, Nrf2, and HO-1 proteins while decreasing the levels of cleaved caspase-3 in renal cells. Conclusion In summary, Tq exhibited protective effects on hyperuricemia-mediated renal oxidative stress and mitochondrial abnormalities which could be mediated by Nrf2/HO-1, Akt signaling pathways.