Thymoquinone enhances kidney function in obesity-induced renal impairment by targeting redox balance, inflammation, autophagy, and apoptosis.

The prevalence of kidney impairment is associated with the consumption of a high-fat diet (HFD) and obesity via the dysregulation of various biological processes. Thymoquinone (TQ) is an active component of black cumin with antioxidant and anti-inflammatory effects. The present study examined the ability of TQ to mitigate kidney injury and assessed the interconnected biological mechanisms that improve kidney function and structure. Adult male rats were fed a HFD for 12 weeks. HFD-fed rats were orally administered TQ from week 9 to week 12. TQ improved kidney function by decreasing the levels of serum creatinine, urea, and uric acid. It also mitigated urinary kidney damage, as indicated by normalization of KIM-1 and NGAL. Moreover, TQ improved both gene expression and protein levels of podocin and nephrin in the kidneys of obese rats. Molecular docking analysis revealed the remarkable ability of TQ to enhance kidney function, TQ maintained antioxidant defense systems and mitigated oxidative stress. Furthermore, TQ suppressed inflammation by decreasing the levels of NF-κB. Moreover, TQ reversed the increase in the levels of autophagy-related proteins by increasing the levels of Beclin-1 and LC3-II and decreasing the level of p62 and cathepsin B in HFD-fed rats. TQ alleviated DNA damage in the kidneys of HFD-fed rats. In addition, the levels of mitochondrial apoptotic mediators improved after treatment with TQ. In conclusion, TQ improved kidney function by targeting key molecular processes by reducing oxidative stress, suppressing inflammatory signals, regulating cellular recycling via autophagy, repressing DNA damage and preventing apoptosis.