Background: Rotenone, a neurotoxin inducing oxidative stress and mitochondrial dysfunction, causes significant kidney damage. Thymoquinone (TQ) from Nigella sativa and Madecassoside (MD) from Centella asiatica are natural compounds with established antioxidant and anti-inflammatory properties. While their individual nephroprotective potentials are known, their combined effect on rotenone-induced kidney injury is unexplored. This study evaluates the impact of TQ and MD, alone and in combination, on renal histopathology in rotenone-induced mice.

Methods: A true experimental, posttest-only control group design will use male Swiss mice as a research object divided into eight groups. Treatments include negative control, rotenone-induced positive control (2.5 mg/kg SC), rotenone with individual TQ (15 mg/kg oral) or MD (15 mg/kg oral), rotenone with varying TQ/MD combinations (TQ 7.5, 10, 15 mg/kg + MD 15 mg/kg oral), and Pramipexole as a control medicine. Kidneys will be harvested on day 20, processed, and stained with Hematoxylin-Eosin. Histopathological assessment will quantify tubular necrosis and glomerular atrophy. Statistical analysis will use One Way ANOVA and Post Hoc tests.

Expected Outcomes: This research anticipates revealing rotenone induced histopathological changes in renal tubules and glomeruli. It will assess the nephroprotective effect of Thymoquinone and Madecassoside, individually and synergistically, offering novel insights for developing therapeutic strategies against toxin-induced kidney damage.