Dose-related effects of eugenol: Exploring renal functionality and morphology in healthy Wistar rats

Eugenol has pharmacological properties, but its impact on renal function is limitedly studied. Thus, this study evaluated the effects of eugenol at 10, 20, and 40 mg kg^-1, administered via gavage for 60 days, on histological, biochemical, oxidative, and proteomic parameters in rat kidneys. Adult Wistar rats treated with 10 mg kg^-1 of eugenol had kidneys with low total antioxidant capacity, high nitric oxide content, and high percentual of blood vessels, with no damage to renal function or morphology. The kidney proteome revealed an upregulation of proteins associated with energy metabolism, oxidative stress, and mitochondrial function. Eugenol at 20 mg kg^-1 did not alter kidney histology but inhibited Na⁺/K⁺ ATPase activity. This dose elicited an upregulation of proteins associated with mitochondrial function and cellular defense. Finally, 40 mg kg^-1 eugenol had more pronounced effects on the kidney, increasing serum sodium, potassium, and chloride levels, inhibiting Na⁺/K⁺ ATPase activity, triggering an adaptive response to oxidative stress, and showing apical brush border thinness in proximal tubules. We concluded that eugenol exerted dose-dependent effects on kidney function and morphology. These findings highlight the importance of careful consideration of eugenol's dosage in therapeutic applications.