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Daidzein attenuates urinary bladder dysfunction in streptozotocin-induced diabetes in rats by NOX-4 and RAC-1 inhibition

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Abstract

Reactive oxygen species via NADPH oxidase (NOX) activation are involved in the pathogenesis of many disease conditions such as diabetes and its complications. In the present study, we have examined the effect of daidzein in the management of diabetic cystopathy. Diabetes was induced in male Sprague Dawley rats via intraperitoneal injection of streptozotocin (STZ) at a dose of 55 mg/kg. After 6 weeks of diabetes induction, animals were treated with daidzein orally at a dose of 25, 50, and 100 mg/kg for 4 weeks. Diabetic animals showed increase (p < 0.001) in bladder capacity (4.32 ± 0.43 mL) and residual volume (2.53 ± 0.19 mL) when compared with normal control animals (2.10 ± 0.40 mL and 0.51 ± 0.12 mL res). Treatment with daidzein at dose of 50 and 100 mg/kg significantly reduced the elevated bladder capacity (2.91 ± 0.11 mL, p < 0.01 and 2.65 ± 1.13 mL, p < 0.001) and residual volume (1.40 ± 0.15 mL, p < 0.001 and 1.15 ± 0.05 mL, p < 0.001). Daidzein-treated animals also showed improvement in voiding efficiency. Elevated threshold and baseline pressure were also found to be reduced in diabetic animals after 4 weeks of daidzein treatment. Daidzein treatment also prevented the loss of antioxidant enzymes in the urinary bladder and also reduced the expression of NOX-4 and RAC-1 in the bladder. From the results, it can be concluded that daidzein showed a beneficial effect on urinary bladder dysfunction in diabetic animals.

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The authors are thankful to Dr. Shailesh Khade for technical help in the surgical procedure.

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YK and AL designed the experiments. AL conducted the experiments. AL and YK interpreted the results and wrote the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Yogesh A. Kulkarni.

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The experimental protocol was reviewed and approved by the Institutional Animal Ethics Committee (IAEC) (approval no: CPCSEA/IAEC/P-75/2018).

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Laddha, A.P., Kulkarni, Y.A. Daidzein attenuates urinary bladder dysfunction in streptozotocin-induced diabetes in rats by NOX-4 and RAC-1 inhibition. Naunyn-Schmiedeberg's Arch Pharmacol 395, 975–986 (2022). https://doi.org/10.1007/s00210-022-02246-y

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