Abstract

NOOTKATONE ATTENUATES HFD/STZ-INDUCED RENAL INFLAMMATION AND OXIDATIVE STRESS

Khloud A. Nagy*, Mirhan N. Makled and Nashwa M. Abu-Elsaad

ABSTRACT

Oxidative stress and subsequent inflammation triggered by streptozotocin (STZ) administration and a high-fat diet (HFD) are major contributors to the progression of renal damage, primarily through the activation of various pathological pathways. This study aimed to investigate the potential renoprotective effects of nootkatone (NTK) against STZ/HFD-induced renal inflammation and oxidative stress. Male rats were randomly assigned to four groups: (1) Ctrl group, (2) STZ+HFD group; rats received STZ (35 mg/kg, i.p.) on weeks 5 and 6 along with HFD for 12 weeks, and (3) STZ+HFD+NTK3 (4) STZ+HFD+NTK10 groups; rats treated with NTK at doses of 3 mg/kg and 10 mg/kg, respectively for the last 6 weeks. At the end of the study, kidney tissues were collected for biochemical analyses. Results demonstrated that the STZ+HFD group showed a significant reduction of glutathione and an elevation of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), compared to the control group. Treatment with NTK at both doses significantly restored GSH levels and reduced TNF-α and IL-6 levels compared to the diabetic group. These findings suggest that NTK enhances antioxidant defenses and mitigates inflammation, thereby offering protective effects against HFD/STZ-induced renal injury.

Keywords: .