D-Carvone Mitigating Renal Damage and Enhancing Antioxidant Defense in Lithium Induced Nephrotoxicity

Abstract

Lithium-induced nephrotoxicity presents a major health concern due to its detrimental impact on renal function, as is frequently observed in clinical and experimental settings. Despite various efforts to address this issue, effective treatment options remain limited. D-Carvone, a natural compound with antioxidants and anti-inflammatory properties, has demonstrated promise in reducing oxidative stress and inflammation. The present study aimed to explore the therapeutic impact of D-Carvone in alleviating lithium-induced nephrotoxicity, with a particular focus on oxidative stress indicators, apoptosis, inflammation, and histological changes in renal tissue. To this end, a total of 24 male rats were divided into four groups: Control, Lithium, Lithium + D-Carvone (20 mg/kg daily), and D-Carvone alone, with six animals per group. Lithium-induced nephrotoxicity was evaluated over 14 days. Oxidative stress was measured by evaluating malondialdehyde (MDA), glutathione (GSH) levels, and superoxide dismutase (SOD) activity. The expression of Caspase-3, Bcl-2, HO-1, TLR4, NRF2, and NF-κB-p65 was analyzed to assess apoptotic, inflammatory, and oxidative stress pathways. A histopathological examination of the kidney cortex and medulla was conducted. The results revealed that lithium administration caused significant histological damage, increased oxidative stress, and altered apoptotic and inflammatory protein expression. D-Carvone treatment reduced lipid peroxidation, restored apoptotic protein balance, alleviated inflammation, and protected renal tissue. These findings highlight the potential of D-Carvone as an adjuvant therapy for mitigating the nephrotoxic effects of lithium.